Sara Freeman

Calculating the estimated glucose disposal rate (eGDR) as a proxy for the level of insulin resistance may be useful way to determine if someone with type 2 diabetes (T2D) is at risk for having a first stroke, Swedish researchers have found.

purestock/Thinkstock

In a large population-based study, the lower the eGDR score went, the higher the risk for having a first stroke became.

The eGDR score was also predictive of the chance of dying from any or a cardiovascular cause, Alexander Zabala, MD, reported at the annual meeting of the European Association for the Study of Diabetes (Abstract OP 01-4).

The link between insulin resistance and an increased risk for stroke has been known for some time, and not just in people with T2D. However, the current way of determining insulin resistance is not suitable for widespread practice.

“The goal standard technique for measuring insulin resistance is the euglycemic clamp method,” said Dr. Zabala, an internal medical resident at Södersjukhuset hospital and researcher at the Karolinska Institutet in Stockholm.

“For that reason, [the eGDR], a method based on readily available clinical factors – waist circumference, hypertension, and glycosylated hemoglobin was developed,” he explained. Body mass index can also be used in place of waist circumference, he qualified.

The eGDR has already been proven to be very precise in people with type 1 diabetes, said Dr. Zabala, and could be an “excellent tool to measure insulin resistance in a large patient population.”
 

Investigating the link between eGDR and first stroke risk

The aim of the study he presented was to see if changes in the eGDR were associated with changes in the risk of someone with T2D experiencing a first stroke, or dying from a cardiovascular or other cause.

An observational cohort was formed by first considering data on all adult patients with T2D who were logged in the Swedish National Diabetes Registry (NDR) during 2004-2016. Then anyone with a history of stroke, or with any missing data on the clinical variables needed to calculate the eGDR, were excluded.

This resulted in an overall population of 104,697 individuals, aged a mean of 63 years, who had developed T2D at around the age of 59 years. About 44% of the study population were women. The mean eGDR for the whole population was 5.6 mg/kg per min.

The study subjects were grouped according to four eGDR levels: 24,706 were in the lowest quartile of eGDR (less than 4 mg/kg per min), signifying the highest level of insulin resistance, and 18,762 were in the upper quartile of eGDR (greater than 8 mg/kg per min), signifying the lowest level of insulin resistance. The middle two groups had an eGDR between 4 and 6 mg/kg per min (40,187), and 6 and 8 mg/kg/min (21,042).

Data from the NDR were then combined with the Swedish Cause of Death register, the Swedish In-patient Care Diagnoses registry, and the Longitudinal Database for Health Insurance and Labour Market Studies (LISA) to determine the rates of stroke, ischemic stroke, hemorrhagic stroke, all-cause mortality, and cardiovascular mortality.
 

Increasing insulin resistance ups risk for stroke, death

After a median follow-up of 5.6 years, 4% (4,201) of the study population had had a stroke.

“We clearly see an increased occurrence of first-time stroke in the group with the lowest eGDR, indicating worst insulin resistance, in comparison with the group with the highest eGDR, indicating less insulin resistance,” Dr. Zabala reported.

After adjustment for potential confounding factors, including age at baseline, gender, diabetes duration, among other variables, the risk for stroke was lowest in those with a high eGDR value and highest for those with a low eGDR value.

Using individuals with the lowest eGDR (less than 4 mg/kg per min) and thus greatest risk of stroke as the reference, adjusted hazard ratios (aHR) for first-time stroke were: 0.60, 0.68, and 0.77 for those with an eGDR of greater than 8, 6-8, and 4-6 mg/kg per min, respectively.

The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. Regarding hemorrhagic stroke, there was no statistically significant correlation between eGDR levels and stroke occurrence. This was due to the small number of cases recorded.

As for all-cause and cardiovascular mortality, a similar pattern was seen, with higher rates of death linked to increasing insulin resistance. Adjusted hazard ratios according to increasing insulin resistance (decreasing eGDR scores) for all-cause death were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.

A sensitivity analysis, using BMI instead of waist circumference to calculate the eGDR, showed a similar pattern, and “interestingly, a correlation between eGDR levels and risk of hemorrhagic stroke.” Dr. Zabala said.
 

Limitations and take-homes

Of course, this is an observational cohort study, so no conclusions on causality can be made and there are no data on the use of anti-diabetic treatments specifically. But there are strengths such as covering almost all adults with T2D in Sweden and a relatively long-follow-up time.

The findings suggest that “eGDR, which may reflect insulin resistance may be a useful risk marker for stroke and death in people with type 2 diabetes,” said Dr. Zabala.

“You had a very large cohort, and that certainly makes your results very valid,” observed Peter Novodvorsky, MUDr. (Hons), PhD, MRCP, a consultant diabetologist in Trenčín, Slovakia.

Dr. Novodvorsky, who chaired the session, picked up on the lack of information about how many people were taking newer diabetes drugs, such as the glucagon-like peptide 1 receptor antagonists and sodium glucose-lowering transport 2 inhibitors.

“As we all know, these might have protective effects which are not necessarily related to the glucose lowering or insulin resistance-lowering” effects, so could have influenced the results. In terms of how practical the eGDR is for clinical practice, Dr. Zabala observed in a press release: “eGDR could be used to help T2D patients better understand and manage their risk of stroke and death. 

“It could also be of importance in research. In this era of personalized medicine, better stratification of type 2 diabetes patients will help optimize clinical trials and further vital research into treatment, diagnosis, care and prevention.”

The research was a collaboration between the Karolinska Institutet, Gothenburg University and the Swedish National Diabetes Registry. Dr. Zabala and coauthors reported having no conflicts of interest.

Calculating the estimated glucose disposal rate (eGDR) as a proxy for the level of insulin resistance may be useful way to determine if someone with type 2 diabetes (T2D) is at risk for having a first stroke, Swedish researchers have found.

purestock/Thinkstock

In a large population-based study, the lower the eGDR score went, the higher the risk for having a first stroke became.

The eGDR score was also predictive of the chance of dying from any or a cardiovascular cause, Alexander Zabala, MD, reported at the annual meeting of the European Association for the Study of Diabetes (Abstract OP 01-4).

The link between insulin resistance and an increased risk for stroke has been known for some time, and not just in people with T2D. However, the current way of determining insulin resistance is not suitable for widespread practice.

“The goal standard technique for measuring insulin resistance is the euglycemic clamp method,” said Dr. Zabala, an internal medical resident at Södersjukhuset hospital and researcher at the Karolinska Institutet in Stockholm.

“For that reason, [the eGDR], a method based on readily available clinical factors – waist circumference, hypertension, and glycosylated hemoglobin was developed,” he explained. Body mass index can also be used in place of waist circumference, he qualified.

The eGDR has already been proven to be very precise in people with type 1 diabetes, said Dr. Zabala, and could be an “excellent tool to measure insulin resistance in a large patient population.”
 

Investigating the link between eGDR and first stroke risk

The aim of the study he presented was to see if changes in the eGDR were associated with changes in the risk of someone with T2D experiencing a first stroke, or dying from a cardiovascular or other cause.

An observational cohort was formed by first considering data on all adult patients with T2D who were logged in the Swedish National Diabetes Registry (NDR) during 2004-2016. Then anyone with a history of stroke, or with any missing data on the clinical variables needed to calculate the eGDR, were excluded.

This resulted in an overall population of 104,697 individuals, aged a mean of 63 years, who had developed T2D at around the age of 59 years. About 44% of the study population were women. The mean eGDR for the whole population was 5.6 mg/kg per min.

The study subjects were grouped according to four eGDR levels: 24,706 were in the lowest quartile of eGDR (less than 4 mg/kg per min), signifying the highest level of insulin resistance, and 18,762 were in the upper quartile of eGDR (greater than 8 mg/kg per min), signifying the lowest level of insulin resistance. The middle two groups had an eGDR between 4 and 6 mg/kg per min (40,187), and 6 and 8 mg/kg/min (21,042).

Data from the NDR were then combined with the Swedish Cause of Death register, the Swedish In-patient Care Diagnoses registry, and the Longitudinal Database for Health Insurance and Labour Market Studies (LISA) to determine the rates of stroke, ischemic stroke, hemorrhagic stroke, all-cause mortality, and cardiovascular mortality.
 

Increasing insulin resistance ups risk for stroke, death

After a median follow-up of 5.6 years, 4% (4,201) of the study population had had a stroke.

“We clearly see an increased occurrence of first-time stroke in the group with the lowest eGDR, indicating worst insulin resistance, in comparison with the group with the highest eGDR, indicating less insulin resistance,” Dr. Zabala reported.

After adjustment for potential confounding factors, including age at baseline, gender, diabetes duration, among other variables, the risk for stroke was lowest in those with a high eGDR value and highest for those with a low eGDR value.

Using individuals with the lowest eGDR (less than 4 mg/kg per min) and thus greatest risk of stroke as the reference, adjusted hazard ratios (aHR) for first-time stroke were: 0.60, 0.68, and 0.77 for those with an eGDR of greater than 8, 6-8, and 4-6 mg/kg per min, respectively.

The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. Regarding hemorrhagic stroke, there was no statistically significant correlation between eGDR levels and stroke occurrence. This was due to the small number of cases recorded.

As for all-cause and cardiovascular mortality, a similar pattern was seen, with higher rates of death linked to increasing insulin resistance. Adjusted hazard ratios according to increasing insulin resistance (decreasing eGDR scores) for all-cause death were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.

A sensitivity analysis, using BMI instead of waist circumference to calculate the eGDR, showed a similar pattern, and “interestingly, a correlation between eGDR levels and risk of hemorrhagic stroke.” Dr. Zabala said.
 

Limitations and take-homes

Of course, this is an observational cohort study, so no conclusions on causality can be made and there are no data on the use of anti-diabetic treatments specifically. But there are strengths such as covering almost all adults with T2D in Sweden and a relatively long-follow-up time.

The findings suggest that “eGDR, which may reflect insulin resistance may be a useful risk marker for stroke and death in people with type 2 diabetes,” said Dr. Zabala.

“You had a very large cohort, and that certainly makes your results very valid,” observed Peter Novodvorsky, MUDr. (Hons), PhD, MRCP, a consultant diabetologist in Trenčín, Slovakia.

Dr. Novodvorsky, who chaired the session, picked up on the lack of information about how many people were taking newer diabetes drugs, such as the glucagon-like peptide 1 receptor antagonists and sodium glucose-lowering transport 2 inhibitors.

“As we all know, these might have protective effects which are not necessarily related to the glucose lowering or insulin resistance-lowering” effects, so could have influenced the results. In terms of how practical the eGDR is for clinical practice, Dr. Zabala observed in a press release: “eGDR could be used to help T2D patients better understand and manage their risk of stroke and death. 

“It could also be of importance in research. In this era of personalized medicine, better stratification of type 2 diabetes patients will help optimize clinical trials and further vital research into treatment, diagnosis, care and prevention.”

The research was a collaboration between the Karolinska Institutet, Gothenburg University and the Swedish National Diabetes Registry. Dr. Zabala and coauthors reported having no conflicts of interest.

Calculating the estimated glucose disposal rate (eGDR) as a proxy for the level of insulin resistance may be useful way to determine if someone with type 2 diabetes (T2D) is at risk for having a first stroke, Swedish researchers have found.

purestock/Thinkstock

In a large population-based study, the lower the eGDR score went, the higher the risk for having a first stroke became.

The eGDR score was also predictive of the chance of dying from any or a cardiovascular cause, Alexander Zabala, MD, reported at the annual meeting of the European Association for the Study of Diabetes (Abstract OP 01-4).

The link between insulin resistance and an increased risk for stroke has been known for some time, and not just in people with T2D. However, the current way of determining insulin resistance is not suitable for widespread practice.

“The goal standard technique for measuring insulin resistance is the euglycemic clamp method,” said Dr. Zabala, an internal medical resident at Södersjukhuset hospital and researcher at the Karolinska Institutet in Stockholm.

“For that reason, [the eGDR], a method based on readily available clinical factors – waist circumference, hypertension, and glycosylated hemoglobin was developed,” he explained. Body mass index can also be used in place of waist circumference, he qualified.

The eGDR has already been proven to be very precise in people with type 1 diabetes, said Dr. Zabala, and could be an “excellent tool to measure insulin resistance in a large patient population.”
 

Investigating the link between eGDR and first stroke risk

The aim of the study he presented was to see if changes in the eGDR were associated with changes in the risk of someone with T2D experiencing a first stroke, or dying from a cardiovascular or other cause.

An observational cohort was formed by first considering data on all adult patients with T2D who were logged in the Swedish National Diabetes Registry (NDR) during 2004-2016. Then anyone with a history of stroke, or with any missing data on the clinical variables needed to calculate the eGDR, were excluded.

This resulted in an overall population of 104,697 individuals, aged a mean of 63 years, who had developed T2D at around the age of 59 years. About 44% of the study population were women. The mean eGDR for the whole population was 5.6 mg/kg per min.

The study subjects were grouped according to four eGDR levels: 24,706 were in the lowest quartile of eGDR (less than 4 mg/kg per min), signifying the highest level of insulin resistance, and 18,762 were in the upper quartile of eGDR (greater than 8 mg/kg per min), signifying the lowest level of insulin resistance. The middle two groups had an eGDR between 4 and 6 mg/kg per min (40,187), and 6 and 8 mg/kg/min (21,042).

Data from the NDR were then combined with the Swedish Cause of Death register, the Swedish In-patient Care Diagnoses registry, and the Longitudinal Database for Health Insurance and Labour Market Studies (LISA) to determine the rates of stroke, ischemic stroke, hemorrhagic stroke, all-cause mortality, and cardiovascular mortality.
 

Increasing insulin resistance ups risk for stroke, death

After a median follow-up of 5.6 years, 4% (4,201) of the study population had had a stroke.

“We clearly see an increased occurrence of first-time stroke in the group with the lowest eGDR, indicating worst insulin resistance, in comparison with the group with the highest eGDR, indicating less insulin resistance,” Dr. Zabala reported.

After adjustment for potential confounding factors, including age at baseline, gender, diabetes duration, among other variables, the risk for stroke was lowest in those with a high eGDR value and highest for those with a low eGDR value.

Using individuals with the lowest eGDR (less than 4 mg/kg per min) and thus greatest risk of stroke as the reference, adjusted hazard ratios (aHR) for first-time stroke were: 0.60, 0.68, and 0.77 for those with an eGDR of greater than 8, 6-8, and 4-6 mg/kg per min, respectively.

The corresponding values for risk of ischemic stroke were 0.55, 0.68, and 0.75. Regarding hemorrhagic stroke, there was no statistically significant correlation between eGDR levels and stroke occurrence. This was due to the small number of cases recorded.

As for all-cause and cardiovascular mortality, a similar pattern was seen, with higher rates of death linked to increasing insulin resistance. Adjusted hazard ratios according to increasing insulin resistance (decreasing eGDR scores) for all-cause death were 0.68, 0.75, and 0.82 and for cardiovascular mortality were 0.65, 0.75, and 0.82.

A sensitivity analysis, using BMI instead of waist circumference to calculate the eGDR, showed a similar pattern, and “interestingly, a correlation between eGDR levels and risk of hemorrhagic stroke.” Dr. Zabala said.
 

Limitations and take-homes

Of course, this is an observational cohort study, so no conclusions on causality can be made and there are no data on the use of anti-diabetic treatments specifically. But there are strengths such as covering almost all adults with T2D in Sweden and a relatively long-follow-up time.

The findings suggest that “eGDR, which may reflect insulin resistance may be a useful risk marker for stroke and death in people with type 2 diabetes,” said Dr. Zabala.

“You had a very large cohort, and that certainly makes your results very valid,” observed Peter Novodvorsky, MUDr. (Hons), PhD, MRCP, a consultant diabetologist in Trenčín, Slovakia.

Dr. Novodvorsky, who chaired the session, picked up on the lack of information about how many people were taking newer diabetes drugs, such as the glucagon-like peptide 1 receptor antagonists and sodium glucose-lowering transport 2 inhibitors.

“As we all know, these might have protective effects which are not necessarily related to the glucose lowering or insulin resistance-lowering” effects, so could have influenced the results. In terms of how practical the eGDR is for clinical practice, Dr. Zabala observed in a press release: “eGDR could be used to help T2D patients better understand and manage their risk of stroke and death. 

“It could also be of importance in research. In this era of personalized medicine, better stratification of type 2 diabetes patients will help optimize clinical trials and further vital research into treatment, diagnosis, care and prevention.”

The research was a collaboration between the Karolinska Institutet, Gothenburg University and the Swedish National Diabetes Registry. Dr. Zabala and coauthors reported having no conflicts of interest.

Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.

©American Heart Association

In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).

The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).

“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.

Preeclampsia and lupus

“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”

Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.

“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
 

Study design and results

The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.

The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).

Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m², and being older than 35 years.

The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.

The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m² (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).

Only high disease activity in the first trimester and BMI >30 kg/m² remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).

The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.

Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).

“I think that our attitude in looking after lupus patients [changed] during this time,” she said.

“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.

When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”

The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.

©American Heart Association

In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).

The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).

“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.

Preeclampsia and lupus

“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”

Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.

“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
 

Study design and results

The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.

The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).

Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m², and being older than 35 years.

The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.

The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m² (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).

Only high disease activity in the first trimester and BMI >30 kg/m² remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).

The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.

Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).

“I think that our attitude in looking after lupus patients [changed] during this time,” she said.

“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.

When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”

The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.

©American Heart Association

In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).

The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).

“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.

Preeclampsia and lupus

“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”

Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.

“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
 

Study design and results

The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.

The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).

Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m², and being older than 35 years.

The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.

The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m² (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).

Only high disease activity in the first trimester and BMI >30 kg/m² remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).

The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.

Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).

“I think that our attitude in looking after lupus patients [changed] during this time,” she said.

“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.

When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”

The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.

The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.

“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.


 

Multiple conditions “overrepresented” in SLE patients

Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.

The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.

The mean age of the study population was 53 years, 82% were women, and 86% were White.

“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.

A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.

Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.

The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).

Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).

“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
 

Similar findings seen in cutaneous lupus

There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.

Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.

For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.

Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.

“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
 

Comment and perspective

“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.

Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.

She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”

The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.

That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”

Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”

“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.

“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.

These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.

No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.

A version of this article first appeared on Medscape.com.

People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.

The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.

“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.


 

Multiple conditions “overrepresented” in SLE patients

Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.

The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.

The mean age of the study population was 53 years, 82% were women, and 86% were White.

“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.

A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.

Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.

The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).

Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).

“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
 

Similar findings seen in cutaneous lupus

There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.

Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.

For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.

Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.

“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
 

Comment and perspective

“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.

Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.

She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”

The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.

That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”

Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”

“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.

“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.

These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.

No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.

A version of this article first appeared on Medscape.com.

People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.

The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.

“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.


 

Multiple conditions “overrepresented” in SLE patients

Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.

The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.

The mean age of the study population was 53 years, 82% were women, and 86% were White.

“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.

A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.

Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.

The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).

Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).

“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
 

Similar findings seen in cutaneous lupus

There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.

Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.

For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.

Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.

“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
 

Comment and perspective

“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.

Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.

She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”

The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.

That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”

Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”

“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.

“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.

These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.

No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.

A version of this article first appeared on Medscape.com.

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.

“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.

“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.

Prior to the meeting, the study was published in ACR Open Rheumatology.
 

Collating the evidence

Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.

Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.

The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.

ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.

Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
 

Key findings

The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.

That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”

Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.

SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.

“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.

SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”

They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.

Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.  
 

Got lupus? ‘Get vaccinated’

“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”

Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.

Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.  

“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.

This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.

However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.

“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.

The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.

“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”

The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.

The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.

“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).

“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

aPL and adverse obstetric outcomes

aPL, which include lupus anticoagulant, anti–beta₂-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.  

Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.

The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.

“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.

Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).

The full-term live birth rates were a respective 42% and 72% (P < .0001).

The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).

A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.

The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
 

Study highlights ‘impact and importance’ of complement in APS

The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.

In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.

However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.

“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”

Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.

“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.

Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.

The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.

The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.

“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).

“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

aPL and adverse obstetric outcomes

aPL, which include lupus anticoagulant, anti–beta₂-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.  

Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.

The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.

“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.

Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).

The full-term live birth rates were a respective 42% and 72% (P < .0001).

The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).

A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.

The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
 

Study highlights ‘impact and importance’ of complement in APS

The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.

In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.

However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.

“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”

Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.

“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.

Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.

The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.

The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.

“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).

“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.

aPL and adverse obstetric outcomes

aPL, which include lupus anticoagulant, anti–beta₂-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.  

Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.

The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.

“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.

Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).

The full-term live birth rates were a respective 42% and 72% (P < .0001).

The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).

A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.

The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
 

Study highlights ‘impact and importance’ of complement in APS

The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.

In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.

However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.

“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”

Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.

“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.

Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.

The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

People with insulin-treated type 1 diabetes who had problems avoiding hypoglycemic episodes despite optimal care were helped significantly by a new psychoeducational program called HARPdoc, it was reported at the annual meeting of the European Association for the Study of Diabetes.

In a randomized controlled trial (RCT), both HARPdoc and the more established Blood Glucose Awareness Training (BGAT) were effective at reducing the number of severe hypoglycemia episodes seen, from five episodes at baseline to one at 1 year in both groups, and one and none at 2-years’ follow-up, respectively.

“HARPdoc is not superior to BGAT in its ability to restore hypoglycemia awareness and reduce severe hypoglycemia,” said Stephanie Amiel, MD, FRCP, the chief investigator for the trial. However, “it does reduce cognitive barriers to hypoglycemia avoidance, so it achieves what it set out to do.”

Dr. Amiel, professor of diabetes research at Kings College London, added that it was important to note that HARPdoc was better than BGAT at improving participants’ mental health, “producing a clinically important and sustainable reduction in diabetes distress, anxiety, and depression.”
 

What’s HARPdoc?

The Hypoglycaemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc) was designed to specifically address why some people with type 1 diabetes find it difficult to avoid recurrent hypoglycemia.

“It’s a psychoeducational program with clinical knowledge about hypoglycemia and group learning, but also explicit topics on mindset and behavior change,” explained Nicole de Zoysa, DClinPsych, one of the clinical psychologists involved in the trial.

Over the course of the 6-week program, there are four group sessions (weeks 1-3, and week 6) and two individual sessions (weeks 4 and 5) ­that address important “cognitive barriers” or “thinking traps” to avoiding hypoglycemia that were identified during prior qualitative research.

HARPdoc is thus “an attempt to make sense of people’s reluctance or seeming reluctance to take action around hypoglycemia, Dr. de Zoysa said. The intervention draws on both cognitive behavioral theory “to work with the beliefs” and motivational interviewing “to work with the resistance.”
 

The HARPdoc RCT

Starting in 2017 and ending earlier this year, the HARPdoc RCT was a parallel group study conducted at three specialist diabetes centers in the United Kingdom and one in the United States.

A total of 99 adults with insulin-treated type 1 diabetes and impaired hypoglycemia awareness were enrolled – with 49 randomized to the HARPdoc arm and 50 to the BGAT arm. All had been offered technologies to help them potentially bring their hypoglycemia under better control, such as continuous glucose monitoring, insulin pumps, or closed loop systems, and received structured education on flexible insulin dosing.

The aim was to show superiority of the HARPdoc program over BGAT, in helping people avoid episodes of severe hypoglycemia, defined as episodes that needed other people’s intervention to help resolve.

BGAT is also a psychoeducation program that has been around since the 1980s but barely used in the United Kingdom, Dr. Amiel noted.

Baseline demographic characteristics were similar for the HARPdoc and BGAT arms: The mean age was 57 versus 52 years, there was a long (30+ years) duration of diabetes, over half of the participants were male, and almost all were White.
 

Primary endpoint not met, but still ‘impressive’

Although the primary endpoint of the trial was not met, the reductions in severe hypoglycemia seen are still “impressive,” said Ramzi Ajjan, MD, FRCP, of Leeds (England) University and Leeds Teaching Hospitals Trust.

“I was really blown away,” by the improvement in both study arms, said Dr. Ajjan, who was not involved in the trial. “These people have had proper clinical input,” he stressed, noting that both interventions worked, with no difference between them in terms of severe hypoglycemia.

Dr. Ajjan was not surprised by the better cognition scores measured using the A2A questionnaire seen with HARPdoc versus BGAT, as “this is what the intervention was designed to address.”

In terms of the mental health benefits seen, HARPdoc significantly reduced the level of diabetes distress as measured using the Problem Areas In Diabetes (PAID) questionnaire versus the BGAT intervention.

The PAID score was around 30 in both groups at baseline, this fell to about 26 at 1 year, and around 20 at 2 years in the HARPdoc group, which was significantly lower than the score seen in the BGAT group which rose slightly then fell back to baseline levels.

A similar pattern was seen in the levels of depression and anxiety, which were measured by the HADS-D and HADS-A instruments. So HARPdoc was more effective at improving psychological and mental health outcomes than BGAT, Dr. Ajjan observed.

The HARPdoc project is funded by the Juvenile Diabetes Research Foundation with additional support from the UK’s National Institute of Health Research. The HARPdoc RCT was jointly sponsored by King’s College London and King’s College Hospital NHS Foundation Trust. Dr. Amiel has served on advisory panels for Roche, Medtronic, and Novo Nordisk. Dr. de Zoysa did not state having any conflicts of interest. Dr. Ajjan disclosed that he has financial relationships with multiple pharmaceutical companies.

Bone marrow derived autologous cell therapy (ACT) has been shown to significantly reduce the rate of major amputation at 5 years in people with diabetes who developed critical limb-threatening ischemia (CLTI).

In a study of 130 patients, 64% of 42 patients who were treated conservatively needed a major amputation at 5 years versus just 30% of 45 patients who had been treated with ACT (P = .011).

This compared favorably to the results seen with repeated percutaneous angioplasty (re-PTA), where just 20.9% of 43 patients underwent limb salvage (P = .002 vs. conservative therapy).

Furthermore, amputation-free survival was significantly longer in both active groups, Michal Dubský, MD, PhD, FRSPH, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Dubský, of the Institute for Clinical and Experimental Medicine and Charles University in Prague, also reported that fewer patients who had undergone re-PTA or ACT than conservative treatment had died by 5 years (25.8% and 35.6%, respectively, vs. 61.9%), but that the difference was significant only for the revascularization procedure (P = .012).

Based on these findings, “we believe that autologous cell therapy seems to be an appropriate alternative to repeated PTA even for patients with no-option chronic limb-threatening ischemia,” he said.

“This is a very important area,” said Andrew J.M. Boulton, MBBS, MD, FRCP, who chaired the oral abstract presentation session during which the findings were presented.

“It is very difficult to get an evidence base from randomized studies in this area, because of the nature of the patients: They’re very sick and we all deal with them in our clinics very regularly,” added Dr. Boulton, professor of medicine within the division of diabetes, endocrinology and gastroenterology at the University of Manchester (England).

Dr. Boulton called the findings a “very important addition to what we know.”
 

New option for no-option CLTI

CLTI is associated with persistent pain at rest, ulcers, and gangrene, and can be the end result of longstanding peripheral arterial disease. Within the first year of presentation, there’s a 30% chance of having a major amputation and a 25% chance of dying.

Importantly, said Dr. Dubský, “there is a big difference in this diagnosis” between patients with diabetes and those without. For instance, CLTI is more diffuse in patients with diabetes than in those without, different arteries are affected and the sclerosis seen can be more rigid and “full of calcium.”

While surgery to improve blood flow is the standard of care, not everyone is suitable. Bypass surgery or endovascular procedures can be performed in only 40%-50% of patients, and even then a therapeutic effect may be seen in only a quarter of patients.

“We need some new therapeutic modalities for this diagnosis, and one of them could be autologous cell therapy,” said Dr. Dubský.
 

Study details

Dr. Dubský and coinvestigators consecutively recruited 130 patients with diabetic foot and CLTI who had been seen at their clinic over a 5-year period. Of these, 87 had not been eligible for standard revascularization and underwent ACT or were treated conservatively.

Of the patients who were not eligible for standard revascularization (‘no-option CLTI), 45 had undergone ACT and 42 had been treated conservatively. Dr. Dubský acknowledged that “his study was not prospective and randomized.”

All patients in the study had at least one unsuccessful revascularization procedure and diabetic foot ulcers, and low tissue oxygenation. The latter was defined as transcutaneous oxygen pressure (TcPO₂) of below 30 mm Hg.

There were little differences in demographic characteristics between the treatment groups, the average age ranged from 62 to 67 years, there were more men (70%-80%) than women; most patients (90%) had type 2 diabetes for at least 20 years. There were similar rates of ischemic heart disease, hypertension, dialysis, and immunosuppressive therapy.

There were no differences in baseline values of TcPO₂ between the groups, and similar improvements were seen in both the ACT and re-PTA groups versus conservative group.
 

ACT in practice

With such promising results, what about the practicalities of harvesting a patient’s bone marrow to make the ACT?

“Bone marrow harvesting usually takes about 20 minutes,” Dr. Dubský said. It then takes another 45 minutes to separate the cells and make the cell suspension, and then maybe another 10 minutes or so to administer this to the patient, which is done by injecting into the calf muscles and small muscles of the foot, aided by computed tomography. The whole process may take up to 2 hours, he said.

“Patients are under local or general anesthesia, so there is no pain during the procedure,” Dr. Dubský reassured. “Afterwards we sometimes see small hematoma[s], with low-intensity pain that responds well to usual analgesic therapy.”

Computed tomography was used to help guide the injections, which was advantageous, Dr. Boulton pointed out, because it was “less invasive than angioplasty in these very sick people with very distal lesions, many of whom already have renal problems.”

“It is surprising though, that everybody had re-PTA and not one had vascular surgery,” he suggested. Dr. Boulton added, however: “These are very important observations; they help us a lot in an area where there’s unlikely to be a full RCT.”

The next step in this research is to see if combining ACT and re-PTA could lead to even better results.

The study was funded by the Czech Republic Ministry of Health. Dr. Dubský had nothing to disclose. Dr. Boulton made no statement about his conflicts of interest.

Bone marrow derived autologous cell therapy (ACT) has been shown to significantly reduce the rate of major amputation at 5 years in people with diabetes who developed critical limb-threatening ischemia (CLTI).

In a study of 130 patients, 64% of 42 patients who were treated conservatively needed a major amputation at 5 years versus just 30% of 45 patients who had been treated with ACT (P = .011).

This compared favorably to the results seen with repeated percutaneous angioplasty (re-PTA), where just 20.9% of 43 patients underwent limb salvage (P = .002 vs. conservative therapy).

Furthermore, amputation-free survival was significantly longer in both active groups, Michal Dubský, MD, PhD, FRSPH, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Dubský, of the Institute for Clinical and Experimental Medicine and Charles University in Prague, also reported that fewer patients who had undergone re-PTA or ACT than conservative treatment had died by 5 years (25.8% and 35.6%, respectively, vs. 61.9%), but that the difference was significant only for the revascularization procedure (P = .012).

Based on these findings, “we believe that autologous cell therapy seems to be an appropriate alternative to repeated PTA even for patients with no-option chronic limb-threatening ischemia,” he said.

“This is a very important area,” said Andrew J.M. Boulton, MBBS, MD, FRCP, who chaired the oral abstract presentation session during which the findings were presented.

“It is very difficult to get an evidence base from randomized studies in this area, because of the nature of the patients: They’re very sick and we all deal with them in our clinics very regularly,” added Dr. Boulton, professor of medicine within the division of diabetes, endocrinology and gastroenterology at the University of Manchester (England).

Dr. Boulton called the findings a “very important addition to what we know.”
 

New option for no-option CLTI

CLTI is associated with persistent pain at rest, ulcers, and gangrene, and can be the end result of longstanding peripheral arterial disease. Within the first year of presentation, there’s a 30% chance of having a major amputation and a 25% chance of dying.

Importantly, said Dr. Dubský, “there is a big difference in this diagnosis” between patients with diabetes and those without. For instance, CLTI is more diffuse in patients with diabetes than in those without, different arteries are affected and the sclerosis seen can be more rigid and “full of calcium.”

While surgery to improve blood flow is the standard of care, not everyone is suitable. Bypass surgery or endovascular procedures can be performed in only 40%-50% of patients, and even then a therapeutic effect may be seen in only a quarter of patients.

“We need some new therapeutic modalities for this diagnosis, and one of them could be autologous cell therapy,” said Dr. Dubský.
 

Study details

Dr. Dubský and coinvestigators consecutively recruited 130 patients with diabetic foot and CLTI who had been seen at their clinic over a 5-year period. Of these, 87 had not been eligible for standard revascularization and underwent ACT or were treated conservatively.

Of the patients who were not eligible for standard revascularization (‘no-option CLTI), 45 had undergone ACT and 42 had been treated conservatively. Dr. Dubský acknowledged that “his study was not prospective and randomized.”

All patients in the study had at least one unsuccessful revascularization procedure and diabetic foot ulcers, and low tissue oxygenation. The latter was defined as transcutaneous oxygen pressure (TcPO₂) of below 30 mm Hg.

There were little differences in demographic characteristics between the treatment groups, the average age ranged from 62 to 67 years, there were more men (70%-80%) than women; most patients (90%) had type 2 diabetes for at least 20 years. There were similar rates of ischemic heart disease, hypertension, dialysis, and immunosuppressive therapy.

There were no differences in baseline values of TcPO₂ between the groups, and similar improvements were seen in both the ACT and re-PTA groups versus conservative group.
 

ACT in practice

With such promising results, what about the practicalities of harvesting a patient’s bone marrow to make the ACT?

“Bone marrow harvesting usually takes about 20 minutes,” Dr. Dubský said. It then takes another 45 minutes to separate the cells and make the cell suspension, and then maybe another 10 minutes or so to administer this to the patient, which is done by injecting into the calf muscles and small muscles of the foot, aided by computed tomography. The whole process may take up to 2 hours, he said.

“Patients are under local or general anesthesia, so there is no pain during the procedure,” Dr. Dubský reassured. “Afterwards we sometimes see small hematoma[s], with low-intensity pain that responds well to usual analgesic therapy.”

Computed tomography was used to help guide the injections, which was advantageous, Dr. Boulton pointed out, because it was “less invasive than angioplasty in these very sick people with very distal lesions, many of whom already have renal problems.”

“It is surprising though, that everybody had re-PTA and not one had vascular surgery,” he suggested. Dr. Boulton added, however: “These are very important observations; they help us a lot in an area where there’s unlikely to be a full RCT.”

The next step in this research is to see if combining ACT and re-PTA could lead to even better results.

The study was funded by the Czech Republic Ministry of Health. Dr. Dubský had nothing to disclose. Dr. Boulton made no statement about his conflicts of interest.

Bone marrow derived autologous cell therapy (ACT) has been shown to significantly reduce the rate of major amputation at 5 years in people with diabetes who developed critical limb-threatening ischemia (CLTI).

In a study of 130 patients, 64% of 42 patients who were treated conservatively needed a major amputation at 5 years versus just 30% of 45 patients who had been treated with ACT (P = .011).

This compared favorably to the results seen with repeated percutaneous angioplasty (re-PTA), where just 20.9% of 43 patients underwent limb salvage (P = .002 vs. conservative therapy).

Furthermore, amputation-free survival was significantly longer in both active groups, Michal Dubský, MD, PhD, FRSPH, reported at the annual meeting of the European Association for the Study of Diabetes.

Dr. Dubský, of the Institute for Clinical and Experimental Medicine and Charles University in Prague, also reported that fewer patients who had undergone re-PTA or ACT than conservative treatment had died by 5 years (25.8% and 35.6%, respectively, vs. 61.9%), but that the difference was significant only for the revascularization procedure (P = .012).

Based on these findings, “we believe that autologous cell therapy seems to be an appropriate alternative to repeated PTA even for patients with no-option chronic limb-threatening ischemia,” he said.

“This is a very important area,” said Andrew J.M. Boulton, MBBS, MD, FRCP, who chaired the oral abstract presentation session during which the findings were presented.

“It is very difficult to get an evidence base from randomized studies in this area, because of the nature of the patients: They’re very sick and we all deal with them in our clinics very regularly,” added Dr. Boulton, professor of medicine within the division of diabetes, endocrinology and gastroenterology at the University of Manchester (England).

Dr. Boulton called the findings a “very important addition to what we know.”
 

New option for no-option CLTI

CLTI is associated with persistent pain at rest, ulcers, and gangrene, and can be the end result of longstanding peripheral arterial disease. Within the first year of presentation, there’s a 30% chance of having a major amputation and a 25% chance of dying.

Importantly, said Dr. Dubský, “there is a big difference in this diagnosis” between patients with diabetes and those without. For instance, CLTI is more diffuse in patients with diabetes than in those without, different arteries are affected and the sclerosis seen can be more rigid and “full of calcium.”

While surgery to improve blood flow is the standard of care, not everyone is suitable. Bypass surgery or endovascular procedures can be performed in only 40%-50% of patients, and even then a therapeutic effect may be seen in only a quarter of patients.

“We need some new therapeutic modalities for this diagnosis, and one of them could be autologous cell therapy,” said Dr. Dubský.
 

Study details

Dr. Dubský and coinvestigators consecutively recruited 130 patients with diabetic foot and CLTI who had been seen at their clinic over a 5-year period. Of these, 87 had not been eligible for standard revascularization and underwent ACT or were treated conservatively.

Of the patients who were not eligible for standard revascularization (‘no-option CLTI), 45 had undergone ACT and 42 had been treated conservatively. Dr. Dubský acknowledged that “his study was not prospective and randomized.”

All patients in the study had at least one unsuccessful revascularization procedure and diabetic foot ulcers, and low tissue oxygenation. The latter was defined as transcutaneous oxygen pressure (TcPO₂) of below 30 mm Hg.

There were little differences in demographic characteristics between the treatment groups, the average age ranged from 62 to 67 years, there were more men (70%-80%) than women; most patients (90%) had type 2 diabetes for at least 20 years. There were similar rates of ischemic heart disease, hypertension, dialysis, and immunosuppressive therapy.

There were no differences in baseline values of TcPO₂ between the groups, and similar improvements were seen in both the ACT and re-PTA groups versus conservative group.
 

ACT in practice

With such promising results, what about the practicalities of harvesting a patient’s bone marrow to make the ACT?

“Bone marrow harvesting usually takes about 20 minutes,” Dr. Dubský said. It then takes another 45 minutes to separate the cells and make the cell suspension, and then maybe another 10 minutes or so to administer this to the patient, which is done by injecting into the calf muscles and small muscles of the foot, aided by computed tomography. The whole process may take up to 2 hours, he said.

“Patients are under local or general anesthesia, so there is no pain during the procedure,” Dr. Dubský reassured. “Afterwards we sometimes see small hematoma[s], with low-intensity pain that responds well to usual analgesic therapy.”

Computed tomography was used to help guide the injections, which was advantageous, Dr. Boulton pointed out, because it was “less invasive than angioplasty in these very sick people with very distal lesions, many of whom already have renal problems.”

“It is surprising though, that everybody had re-PTA and not one had vascular surgery,” he suggested. Dr. Boulton added, however: “These are very important observations; they help us a lot in an area where there’s unlikely to be a full RCT.”

The next step in this research is to see if combining ACT and re-PTA could lead to even better results.

The study was funded by the Czech Republic Ministry of Health. Dr. Dubský had nothing to disclose. Dr. Boulton made no statement about his conflicts of interest.

Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.

memorisz/iStock/Getty Images

In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.

While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.

The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.

“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.

That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.

However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
 

First data in Norwegian population

Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
 

Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.

The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).

“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.

“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”

Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
 

Rise in retinopathy faster in men than in women

Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.

“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.

In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”

So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.

She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.

“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.

These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.

The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.

Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.

memorisz/iStock/Getty Images

In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.

While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.

The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.

“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.

That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.

However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
 

First data in Norwegian population

Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
 

Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.

The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).

“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.

“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”

Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
 

Rise in retinopathy faster in men than in women

Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.

“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.

In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”

So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.

She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.

“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.

These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.

The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.

Men diagnosed with type 2 diabetes (T2D) by the age of 40 years appear significantly more likely to develop retinopathy than men who are diagnosed at an older age, Norwegian researchers report.

memorisz/iStock/Getty Images

In a cross-sectional study of about 10,000 people, men with young-onset T2D were 72% more likely than men aged 50 years or older to have retinopathy.

While an increased retinopathy risk was also seen in women with young-onset T2D versus older women at first, this difference was not significant after adjusting for various confounding factors.

The effect of young-onset diabetes on retinopathy seems to be gender specific, Katrina Tibballs, MD, of the department of general practice at the University of Oslo, reported at the annual meeting of the European Association for the Study of Diabetes.

“In the unadjusted analysis, the odds ratio for retinopathy was substantially higher in both [young-onset] men [odds ratio, 3.0] and women [OR, 2.46], compared with those 50 or older at diabetes diagnosis,” Dr. Tibballs said.

That relationship was not substantially altered after adjustment for variables such as level of education, country background, gender, and body mass index, with adjusted ORs of 2.56 and 2.55 for men and women, respectively.

However, further adjustment to include current age, duration of diabetes, and blood lipids and glycated hemoglobin levels, led to the difference no longer holding for women (OR, 1.34; 95% confidence interval, 0.95-1.89) as it did for men (OR 1.72; 95% CI, 1.29-2.29).
 

First data in Norwegian population

Cross-sectional data on more than 10,000 people with T2D were used for the analysis. These came from the ROSA4 study, a general practice study conducted across Norway in 2014.
 

Just over 10% of the study population used in the analysis was under the age of 40 years at diagnosis of T2D; 21% were aged between 40 and 49 years, and 69% were at least 50 years old.

The mean age of those with young-onset T2D, defined as a diagnosis before the age of 40 years, was 33 years. These individuals had a longer disease duration than those in the other age groups (11.4 vs. 10.0 vs. 7.8 years).

“Looking at clinical characteristics, we say that individuals [with young-onset T2D] have a higher level of hemoglobin A1c than those with diabetes onset later in life,” Dr. Tibballs said.

“This is despite a substantially higher proportion [being] treated with insulin and fewer on lifestyle interventions alone.”

Gender differences were seen in A1c levels, with men with young-onset T2D having consistently higher levels than women, with levels increasing with diabetes duration.
 

Rise in retinopathy faster in men than in women

Dr. Tibballs reported that, not only did the prevalence of retinopathy rise faster in those of a younger age, but it also rose more quickly in men with young-onset T2D than it in their female counterparts.

“Comparing that [young-onset diabetes] and later-onset diabetes in men and women separately, we see a clearly higher prevalence of retinopathy with increasing diabetes duration for [young-onset] men,” she said.

In women, on the other hand, there was “no clear indication of a higher retinopathy prevalence in [young-onset diabetes], except in those with the longest diabetes duration.”

So, what do the results mean for practice? First, they confirm prior work showing that there is a strong association between retinopathy and age at diagnosis of T2D. Second, they suggest that this is despite intensive glucose-lowering treatment.

She speculated that men with young-onset T2D may have had a delayed diagnosis when compared with women and individuals with later onset diabetes, Dr. Tibballs said.

“This may in turn lead to delayed onset of glucose-lowering treatment, allowing for more time with high glycemic exposure and increased risk of acquiring complications, such as retinopathy at the time of diagnosis, or in the first years after,” said Dr. Tibballs.

These are cross-sectional data, “so we can’t say anything about whether this treatment is sufficient, but it is obviously not reducing HbA1c levels as much as we would like” added Dr. Tibballs, who is a primary care physician and PhD student.

The study was supported by The Norwegian Research Fund for General Practice. Dr. Tibballs had no conflicts of interest to disclose.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

Carrying excess weight is associated with an increased risk for certain heart problems even when there are no metabolic disturbances, data from a large French longitudinal study have shown.

In an analysis of almost 3 million people with no prior heart issues, there was a 34% increased risk for developing heart failure and a 33% increased risk for developing atrial fibrillation, it was reported at the annual meeting of the European Association for the Study of Diabetes.

There appeared to be no increase in the risk for heart attacks, ischemic stroke, or cardiovascular death, but the study’s 5-year follow-up period may have been too short to see such differences.

“Our findings highlight the importance of preventing poor metabolic health,” study investigator Laurent Fauchier, MD, PhD, of Centre Hospitalier Universitaire Trousseau (France), observed in a press release that highlighted his EASD presentation.

“Encouraging weight loss in people with obesity, regardless of whether or not they are ‘metabolically healthy,’ will help prevent atrial fibrillation and heart failure,” he suggested.
 

‘Metabolically healthy obesity’ – a misnomer?

‘Metabolically healthy obesity’, or MHO, has been suggested as a term to describe those who have a body mass index greater than 30 mg/m² but no obvious metabolic abnormalities, such as hypertension, dyslipidemia, or diabetes. It’s a term that could cover around a third of people with obesity, but it’s one that not everyone agrees with.

“I don’t feel the label ‘MHO’ is useful,” Frederick Ho, PhD, who is part of team at the University of Glasgow (Scotland) that has done similar research in a U.K. population, said in an interview.

Courtesy Dr. Ho

“Even if – and this is a big if– [people with obesity] are at no higher risk of heart attack or stroke, they are still at higher risk of many other diseases, including heart failure and respiratory diseases. The term ‘healthy’ is sometimes interpreted as no additional health risk at all, which is not true,” Dr. Ho, a research fellow in public health, qualified.
 

Hospital discharge records checked

For their analysis Dr. Fauchier and coinvestigators obtained the medical records of all patients who had been discharged from French hospitals in 2013 and who had at least 5 years’ worth of follow-up data. For inclusion, there had to be no prior history of major cardiovascular events (MACE), which included myocardial infarction (MI), heart failure, and ischemic stroke. Patients who were underweight or malnourished were excluded.

In all, around 2.8 million patients were included for the analysis, of whom 9.5% (n = 272,838) were classified as being obese and the remainder as ‘nonobese’ (n = 2,600,201). Patients were then subdivided according to whether they had diabetes, hypertension, and hyperlipidemia, with those who did not have any of these conditions being classified as ‘metabolically healthy’ and those who had all three as ‘metabolically unhealthy.’

The results, published in Diabetes, Obesity and Metabolism, showed that just under a third (32.8%) of the obese patients were ‘metabolically healthy,’ compared with 72.7% of those who were not obese.

The adjusted hazard ratio (aHR) for experiencing MACE with heart failure was 1.22 comparing those who were obese and ‘metabolically healthy’ with those who were not obese and had no metabolic abnormalities (95% confidence interval, 1.19-1.24). Corresponding aHRs for new-onset heart failure and new-onset atrial fibrillation were 1.34 (CI, 1.31-1.37) and 1.33 (CI, 1.30-1.37). For MI, ischemic stroke, and cardiovascular death aHRs were a respective 0.92 (CI, 0.87-0.98), 0.93 (CI, 0.88-0.98), and 0.99 (CI, 0.93-1.0).
 

Findings consistent with UK Biobank data

While these are observational associations that do not show cause and effect, they do agree with other recently published data from the UK Biobank as Dr. Ho pointed out. These data are “quite interesting and partly consistent with what we found previously, e.g., a higher heart failure risk,” he said.

“We’d expect people with ‘metabolically healthy’ obesity to develop heart attack and stroke a little later than those who were initially metabolically unhealthy,” Dr. Ho noted, observing that the study was very large, but it does has a relatively short period of follow up.

“This is partly because quite a few of those with ‘MHO’ would become metabolically unhealthy after a few years,” Dr. Ho added.

Importantly, he noted, “this study has omitted several important confounders, such as physical activity and diet, which are both strong predictors of MHO and cardiovascular outcomes.”

Naveed Sattar, FMedSci, FRCPath, FRCPGlas, FRSE, professor and honorary consultant in cardiovascular and medical sciences at the University of Glasgow, with whom Dr. Ho has collaborated, gave his thoughts on the topic in an interview.

“Carrying excess weight can give considerable risks for conditions such as heart failure or respiratory disease in ways (not yet fully understood) that are not captured by metabolic health factors,” he said.

“This means that even if someone were to be labeled as living with metabolically healthy obesity, losing weight may still benefit that individual in many ways and reduce their risk of several other important health outcomes. They may also feel better.” 

Furthermore, he added: “Our Glasgow team has therefore strongly cautioned on the use of the term metabolically healthy obesity, and these new data do not change our view.”

Dr. Fauchier has acted as a speaker or consultant for AstraZeneca, Bayer, Bristol Myers Squibb Pfizer, Boehringer Ingelheim, Medtronic, Novartis, and XO. Dr. Ho had no relevant conflicts of interest. Dr. Sattar has received grants and personal fees from Boehringer Ingelheim, and personal fees from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi.

When it comes to protecting diabetic hearts, sodium-glucose cotransporter-2 (SGLT2) inhibitors may have a slight edge over glucagonlike peptide-1 receptor agonists (GLP-1 RAs) according to the results of large, population-based, observational cohort study.

Around a 30% reduction in the risk for being hospitalized for heart failure was achieved in people with type 2 diabetes who were treated with a SGLT2 inhibitor over a GLP-1 RA regardless of whether the patients had a preexisting heart condition.

The findings, published in the Annals of Internal Medicine, also showed a 10% lower risk for myocardial infarction or stroke among those treated with a SGLT2 inhibitor who had preexisting cardiovascular disease (CVD), although there was no difference in risk between the two classes of drugs in those without preexisting CVD.

“These findings are important as they suggest that SGLT2 [inhibitors] and GLP-1 RA offer similar benefits in preventing myocardial infarction and stroke in patients with diabetes,” said study investigator Elisabetta Patorno, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, in an interview.

They also show “that SGLT2 [inhibitors] offer greater efficacy in preventing heart failure, which supports the existing guidelines,” she added.

Paul S. Jellinger, MD, MACE, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said these data were likely to be “additive to guidelines but not transformative.” The overall analysis results were “not surprising.” It was not unexpected that SGLT2 inhibitors provided a robust chronic heart failure (CHF) benefit, particularly in individuals with history of CVD, he said.

Dr. Jellinger, a clinical endocrinologist and professor of clinical medicine on the voluntary faculty at the University of Miami, observed, however, that “the similar CVD benefit in both drug classes in patients without known CVD adds to our knowledge in this somewhat controversial area and may be useful to the clinician in evaluating therapy in a diabetic individual without evidence of or at high risk for CHF.”

Furthermore, “the study also reminds us that, as demonstrated in published meta-analysis, there is also a modest CHF benefit associated with GLP-1 RA treatment particularly in patients with a history of CVD.”
 

Addressing the knowledge gap

Thanks to the results of many large-scale, prospective, cardiovascular outcomes studies, both SGLT2 inhibitors and GLP1 RA have been recommended as treatment for people with diabetes who have established CVD. But with no direct head-to-head trials having been conducted, there is a gap in knowledge and there is currently little guidance for physicians on which drug class to choose for an individual patient.

To try to clarify things, Dr. Patorno and associates looked at data from more than 370,000 people with type 2 diabetes who had been treated between April 2013 and December 2017 with either a SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or GLP-1 RA (albiglutide, dulaglutide, exenatide, or liraglutide).

One-to-one propensity score matching was used to create the study groups: participants were first grouped according to their history of CVD, and then by the class of drug they had been prescribed. The primary outcomes were hospitalization for MI, stroke, or heart failure.

Comparing the initiation of a SGLT2 inhibitor with GLP-1 RA therapy, the hazard ratios (HRs) for MI or stroke in patients with and without a history of CVD were a respective 0.90 (95% CI, 0.82 to 0.98) and 1.07 (0.97 to 1.18).

The corresponding hazard ratios for heart failure hospitalizations were 0.71 (0.64 to 0.79) and 0.69 (0.56 to 0.85).
 

Real-world studies are of ‘increasing value’

“As in other not-randomized studies based on real-world data, residual confounding cannot be completely ruled out,” Dr. Patorno acknowledged. She added, however that “state-of-the-art methodological strategies were implemented to minimize this possibility.”

Limitations notwithstanding, “real world studies are demonstrating increasing value,” observed Dr. Jellinger. Further large-scale cardiovascular outcomes trials that directly compare these two drug classes “are unlikely given the depth of information available now,” Dr. Jellinger suggested.

“This head-to-head retrospective study may be as close as we get and does represent the first effort at a comparison of these two classes.”

Dr. Patorno said of the potential clinical implications: “Because the two classes are equally effective for stroke and myocardial infarction, but the SGLT2 inhibitors are superior for heart failure, when considered in aggregate, SGLT2 inhibitors are likely to prevent more of these adverse cardiovascular events than GLP-1 RA.”

The study received no commercial funding and was supported by the Brigham and Women’s Hospital and Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics.

Dr. Patorno reported no conflicts of interest. Dr. Jellinger is on the speaker’s bureau for Astra Zeneca, Amgen, and Esperion, and has served on advisory boards for Corcept and Regeneron.

When it comes to protecting diabetic hearts, sodium-glucose cotransporter-2 (SGLT2) inhibitors may have a slight edge over glucagonlike peptide-1 receptor agonists (GLP-1 RAs) according to the results of large, population-based, observational cohort study.

Around a 30% reduction in the risk for being hospitalized for heart failure was achieved in people with type 2 diabetes who were treated with a SGLT2 inhibitor over a GLP-1 RA regardless of whether the patients had a preexisting heart condition.

The findings, published in the Annals of Internal Medicine, also showed a 10% lower risk for myocardial infarction or stroke among those treated with a SGLT2 inhibitor who had preexisting cardiovascular disease (CVD), although there was no difference in risk between the two classes of drugs in those without preexisting CVD.

“These findings are important as they suggest that SGLT2 [inhibitors] and GLP-1 RA offer similar benefits in preventing myocardial infarction and stroke in patients with diabetes,” said study investigator Elisabetta Patorno, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, in an interview.

They also show “that SGLT2 [inhibitors] offer greater efficacy in preventing heart failure, which supports the existing guidelines,” she added.

Paul S. Jellinger, MD, MACE, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said these data were likely to be “additive to guidelines but not transformative.” The overall analysis results were “not surprising.” It was not unexpected that SGLT2 inhibitors provided a robust chronic heart failure (CHF) benefit, particularly in individuals with history of CVD, he said.

Dr. Jellinger, a clinical endocrinologist and professor of clinical medicine on the voluntary faculty at the University of Miami, observed, however, that “the similar CVD benefit in both drug classes in patients without known CVD adds to our knowledge in this somewhat controversial area and may be useful to the clinician in evaluating therapy in a diabetic individual without evidence of or at high risk for CHF.”

Furthermore, “the study also reminds us that, as demonstrated in published meta-analysis, there is also a modest CHF benefit associated with GLP-1 RA treatment particularly in patients with a history of CVD.”
 

Addressing the knowledge gap

Thanks to the results of many large-scale, prospective, cardiovascular outcomes studies, both SGLT2 inhibitors and GLP1 RA have been recommended as treatment for people with diabetes who have established CVD. But with no direct head-to-head trials having been conducted, there is a gap in knowledge and there is currently little guidance for physicians on which drug class to choose for an individual patient.

To try to clarify things, Dr. Patorno and associates looked at data from more than 370,000 people with type 2 diabetes who had been treated between April 2013 and December 2017 with either a SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or GLP-1 RA (albiglutide, dulaglutide, exenatide, or liraglutide).

One-to-one propensity score matching was used to create the study groups: participants were first grouped according to their history of CVD, and then by the class of drug they had been prescribed. The primary outcomes were hospitalization for MI, stroke, or heart failure.

Comparing the initiation of a SGLT2 inhibitor with GLP-1 RA therapy, the hazard ratios (HRs) for MI or stroke in patients with and without a history of CVD were a respective 0.90 (95% CI, 0.82 to 0.98) and 1.07 (0.97 to 1.18).

The corresponding hazard ratios for heart failure hospitalizations were 0.71 (0.64 to 0.79) and 0.69 (0.56 to 0.85).
 

Real-world studies are of ‘increasing value’

“As in other not-randomized studies based on real-world data, residual confounding cannot be completely ruled out,” Dr. Patorno acknowledged. She added, however that “state-of-the-art methodological strategies were implemented to minimize this possibility.”

Limitations notwithstanding, “real world studies are demonstrating increasing value,” observed Dr. Jellinger. Further large-scale cardiovascular outcomes trials that directly compare these two drug classes “are unlikely given the depth of information available now,” Dr. Jellinger suggested.

“This head-to-head retrospective study may be as close as we get and does represent the first effort at a comparison of these two classes.”

Dr. Patorno said of the potential clinical implications: “Because the two classes are equally effective for stroke and myocardial infarction, but the SGLT2 inhibitors are superior for heart failure, when considered in aggregate, SGLT2 inhibitors are likely to prevent more of these adverse cardiovascular events than GLP-1 RA.”

The study received no commercial funding and was supported by the Brigham and Women’s Hospital and Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics.

Dr. Patorno reported no conflicts of interest. Dr. Jellinger is on the speaker’s bureau for Astra Zeneca, Amgen, and Esperion, and has served on advisory boards for Corcept and Regeneron.

When it comes to protecting diabetic hearts, sodium-glucose cotransporter-2 (SGLT2) inhibitors may have a slight edge over glucagonlike peptide-1 receptor agonists (GLP-1 RAs) according to the results of large, population-based, observational cohort study.

Around a 30% reduction in the risk for being hospitalized for heart failure was achieved in people with type 2 diabetes who were treated with a SGLT2 inhibitor over a GLP-1 RA regardless of whether the patients had a preexisting heart condition.

The findings, published in the Annals of Internal Medicine, also showed a 10% lower risk for myocardial infarction or stroke among those treated with a SGLT2 inhibitor who had preexisting cardiovascular disease (CVD), although there was no difference in risk between the two classes of drugs in those without preexisting CVD.

“These findings are important as they suggest that SGLT2 [inhibitors] and GLP-1 RA offer similar benefits in preventing myocardial infarction and stroke in patients with diabetes,” said study investigator Elisabetta Patorno, MD, DrPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, in an interview.

They also show “that SGLT2 [inhibitors] offer greater efficacy in preventing heart failure, which supports the existing guidelines,” she added.

Paul S. Jellinger, MD, MACE, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said these data were likely to be “additive to guidelines but not transformative.” The overall analysis results were “not surprising.” It was not unexpected that SGLT2 inhibitors provided a robust chronic heart failure (CHF) benefit, particularly in individuals with history of CVD, he said.

Dr. Jellinger, a clinical endocrinologist and professor of clinical medicine on the voluntary faculty at the University of Miami, observed, however, that “the similar CVD benefit in both drug classes in patients without known CVD adds to our knowledge in this somewhat controversial area and may be useful to the clinician in evaluating therapy in a diabetic individual without evidence of or at high risk for CHF.”

Furthermore, “the study also reminds us that, as demonstrated in published meta-analysis, there is also a modest CHF benefit associated with GLP-1 RA treatment particularly in patients with a history of CVD.”
 

Addressing the knowledge gap

Thanks to the results of many large-scale, prospective, cardiovascular outcomes studies, both SGLT2 inhibitors and GLP1 RA have been recommended as treatment for people with diabetes who have established CVD. But with no direct head-to-head trials having been conducted, there is a gap in knowledge and there is currently little guidance for physicians on which drug class to choose for an individual patient.

To try to clarify things, Dr. Patorno and associates looked at data from more than 370,000 people with type 2 diabetes who had been treated between April 2013 and December 2017 with either a SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or GLP-1 RA (albiglutide, dulaglutide, exenatide, or liraglutide).

One-to-one propensity score matching was used to create the study groups: participants were first grouped according to their history of CVD, and then by the class of drug they had been prescribed. The primary outcomes were hospitalization for MI, stroke, or heart failure.

Comparing the initiation of a SGLT2 inhibitor with GLP-1 RA therapy, the hazard ratios (HRs) for MI or stroke in patients with and without a history of CVD were a respective 0.90 (95% CI, 0.82 to 0.98) and 1.07 (0.97 to 1.18).

The corresponding hazard ratios for heart failure hospitalizations were 0.71 (0.64 to 0.79) and 0.69 (0.56 to 0.85).
 

Real-world studies are of ‘increasing value’

“As in other not-randomized studies based on real-world data, residual confounding cannot be completely ruled out,” Dr. Patorno acknowledged. She added, however that “state-of-the-art methodological strategies were implemented to minimize this possibility.”

Limitations notwithstanding, “real world studies are demonstrating increasing value,” observed Dr. Jellinger. Further large-scale cardiovascular outcomes trials that directly compare these two drug classes “are unlikely given the depth of information available now,” Dr. Jellinger suggested.

“This head-to-head retrospective study may be as close as we get and does represent the first effort at a comparison of these two classes.”

Dr. Patorno said of the potential clinical implications: “Because the two classes are equally effective for stroke and myocardial infarction, but the SGLT2 inhibitors are superior for heart failure, when considered in aggregate, SGLT2 inhibitors are likely to prevent more of these adverse cardiovascular events than GLP-1 RA.”

The study received no commercial funding and was supported by the Brigham and Women’s Hospital and Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics.

Dr. Patorno reported no conflicts of interest. Dr. Jellinger is on the speaker’s bureau for Astra Zeneca, Amgen, and Esperion, and has served on advisory boards for Corcept and Regeneron.