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Thyroid dysfunction early in pregnancy may increase risk of gestational diabetes, results of a longitudinal study suggest.

Increased levels of free triiodothyronine (fT3) and the ratio of fT3 to free thyroxine (fT4) were associated with increased risk of this common metabolic complication of pregnancy, study authors reported in the Journal of Clinical Endocrinology & Metabolism.

“To our knowledge, this is the first study to identify fT3 and the fT3:fT4 ratio measured early in pregnancy as independent risk factors of gestational diabetes,” wrote Shristi Rawal, PhD, of the National Institute of Child Health and Human Development (NICHD) , and her colleagues.

Although routine thyroid function screening during pregnancy remains controversial, Dr. Rawal and colleagues said their results support the “potential benefits” of the practice, particularly in light of other recent evidence suggesting thyroid-related adverse pregnancy outcomes.

The current case control study by Dr. Rawal and her coinvestigators included 107 women with gestational diabetes and 214 nongestational diabetes controls selected from a 12-center pregnancy cohort, which included 2,802 women aged between 18 and 40 years. The thyroid markers fT3, fT4, and thyroid-stimulating hormone (TSH) were measured at four pregnancy visits, including first trimester (weeks 10-14) and second trimester (weeks 15-26).

The fT3:fT4 ratio had the strongest association with gestational diabetes. In the second trimester measurement, women in the highest quartile had an almost 14-fold increase in risk when compared to the lowest quartile, after adjusting for potential confounders including prepregnancy body mass index and diabetes family history (adjusted odds ratio, 13.60; 95% confidence interval, 3.97-46.30), Dr. Rawal and her colleagues reported. The ratio of fT3:fT4 at the first trimester was also associated with increased risk (aOR, 8.63; 95% CI, 2.87-26.00).

Similarly, fT3 was positively associated with gestational diabetes at the first trimester (aOR, 4.25; 95% CI, 1.67-10.80) and second trimester (aOR, 3.89; 95% CI, 1.50-10.10), investigators reported.

By contrast, there was no association between fT4 or TSH and gestational diabetes, they found.

“These findings, in combination with previous evidence of thyroid-related adverse pregnancy outcomes, support the benefits of thyroid screening among pregnant women in early to mid pregnancy,” senior author Cuilin Zhang, MD, MPH, PhD, of the NICHD, said in a press statement.

Thyroid function abnormalities are relatively common in pregnant women and have been associated with obstetric complications such as pregnancy loss and premature delivery, investigators noted.

Previous evidence is sparse regarding a potential link between thyroid dysfunction and gestational diabetes. There are some prospective studies that show women with hypothyroidism have an increased incidence of gestational diabetes, Dr. Rawal and her colleagues wrote. Isolated hypothyroxinema, or normal TSH and low fT4, has also been linked to increased risk in some studies, but not in others, they added.

Support for the study came from NICHD and the American Recovery and Reinvestment Act research grants. The authors reported no conflicts of interest.

SOURCE: Rawal S et al. J Clin Endocrinol Metab. 2018 Jun 7. doi: 10.1210/jc.2017-024421.

Thyroid dysfunction early in pregnancy may increase risk of gestational diabetes, results of a longitudinal study suggest.

Increased levels of free triiodothyronine (fT3) and the ratio of fT3 to free thyroxine (fT4) were associated with increased risk of this common metabolic complication of pregnancy, study authors reported in the Journal of Clinical Endocrinology & Metabolism.

“To our knowledge, this is the first study to identify fT3 and the fT3:fT4 ratio measured early in pregnancy as independent risk factors of gestational diabetes,” wrote Shristi Rawal, PhD, of the National Institute of Child Health and Human Development (NICHD) , and her colleagues.

Although routine thyroid function screening during pregnancy remains controversial, Dr. Rawal and colleagues said their results support the “potential benefits” of the practice, particularly in light of other recent evidence suggesting thyroid-related adverse pregnancy outcomes.

The current case control study by Dr. Rawal and her coinvestigators included 107 women with gestational diabetes and 214 nongestational diabetes controls selected from a 12-center pregnancy cohort, which included 2,802 women aged between 18 and 40 years. The thyroid markers fT3, fT4, and thyroid-stimulating hormone (TSH) were measured at four pregnancy visits, including first trimester (weeks 10-14) and second trimester (weeks 15-26).

The fT3:fT4 ratio had the strongest association with gestational diabetes. In the second trimester measurement, women in the highest quartile had an almost 14-fold increase in risk when compared to the lowest quartile, after adjusting for potential confounders including prepregnancy body mass index and diabetes family history (adjusted odds ratio, 13.60; 95% confidence interval, 3.97-46.30), Dr. Rawal and her colleagues reported. The ratio of fT3:fT4 at the first trimester was also associated with increased risk (aOR, 8.63; 95% CI, 2.87-26.00).

Similarly, fT3 was positively associated with gestational diabetes at the first trimester (aOR, 4.25; 95% CI, 1.67-10.80) and second trimester (aOR, 3.89; 95% CI, 1.50-10.10), investigators reported.

By contrast, there was no association between fT4 or TSH and gestational diabetes, they found.

“These findings, in combination with previous evidence of thyroid-related adverse pregnancy outcomes, support the benefits of thyroid screening among pregnant women in early to mid pregnancy,” senior author Cuilin Zhang, MD, MPH, PhD, of the NICHD, said in a press statement.

Thyroid function abnormalities are relatively common in pregnant women and have been associated with obstetric complications such as pregnancy loss and premature delivery, investigators noted.

Previous evidence is sparse regarding a potential link between thyroid dysfunction and gestational diabetes. There are some prospective studies that show women with hypothyroidism have an increased incidence of gestational diabetes, Dr. Rawal and her colleagues wrote. Isolated hypothyroxinema, or normal TSH and low fT4, has also been linked to increased risk in some studies, but not in others, they added.

Support for the study came from NICHD and the American Recovery and Reinvestment Act research grants. The authors reported no conflicts of interest.

SOURCE: Rawal S et al. J Clin Endocrinol Metab. 2018 Jun 7. doi: 10.1210/jc.2017-024421.

Thyroid dysfunction early in pregnancy may increase risk of gestational diabetes, results of a longitudinal study suggest.

Increased levels of free triiodothyronine (fT3) and the ratio of fT3 to free thyroxine (fT4) were associated with increased risk of this common metabolic complication of pregnancy, study authors reported in the Journal of Clinical Endocrinology & Metabolism.

“To our knowledge, this is the first study to identify fT3 and the fT3:fT4 ratio measured early in pregnancy as independent risk factors of gestational diabetes,” wrote Shristi Rawal, PhD, of the National Institute of Child Health and Human Development (NICHD) , and her colleagues.

Although routine thyroid function screening during pregnancy remains controversial, Dr. Rawal and colleagues said their results support the “potential benefits” of the practice, particularly in light of other recent evidence suggesting thyroid-related adverse pregnancy outcomes.

The current case control study by Dr. Rawal and her coinvestigators included 107 women with gestational diabetes and 214 nongestational diabetes controls selected from a 12-center pregnancy cohort, which included 2,802 women aged between 18 and 40 years. The thyroid markers fT3, fT4, and thyroid-stimulating hormone (TSH) were measured at four pregnancy visits, including first trimester (weeks 10-14) and second trimester (weeks 15-26).

The fT3:fT4 ratio had the strongest association with gestational diabetes. In the second trimester measurement, women in the highest quartile had an almost 14-fold increase in risk when compared to the lowest quartile, after adjusting for potential confounders including prepregnancy body mass index and diabetes family history (adjusted odds ratio, 13.60; 95% confidence interval, 3.97-46.30), Dr. Rawal and her colleagues reported. The ratio of fT3:fT4 at the first trimester was also associated with increased risk (aOR, 8.63; 95% CI, 2.87-26.00).

Similarly, fT3 was positively associated with gestational diabetes at the first trimester (aOR, 4.25; 95% CI, 1.67-10.80) and second trimester (aOR, 3.89; 95% CI, 1.50-10.10), investigators reported.

By contrast, there was no association between fT4 or TSH and gestational diabetes, they found.

“These findings, in combination with previous evidence of thyroid-related adverse pregnancy outcomes, support the benefits of thyroid screening among pregnant women in early to mid pregnancy,” senior author Cuilin Zhang, MD, MPH, PhD, of the NICHD, said in a press statement.

Thyroid function abnormalities are relatively common in pregnant women and have been associated with obstetric complications such as pregnancy loss and premature delivery, investigators noted.

Previous evidence is sparse regarding a potential link between thyroid dysfunction and gestational diabetes. There are some prospective studies that show women with hypothyroidism have an increased incidence of gestational diabetes, Dr. Rawal and her colleagues wrote. Isolated hypothyroxinema, or normal TSH and low fT4, has also been linked to increased risk in some studies, but not in others, they added.

Support for the study came from NICHD and the American Recovery and Reinvestment Act research grants. The authors reported no conflicts of interest.

SOURCE: Rawal S et al. J Clin Endocrinol Metab. 2018 Jun 7. doi: 10.1210/jc.2017-024421.

WASHINGTON – Mortality after revisional bariatric procedures remains rare but may be more common than the literature suggests, and appears to be rising in recent years, according to two studies presented at the annual Digestive Disease Week^®.

Violeta B. Popov, MD, of New York University, and a team of researchers used the Nationwide Inpatient Sample (NIS) to look at mortality risk, costs, and risk factors for complications in revisional bariatric procedures.

In one presentation, Dr. Popov noted that revision after bariatric surgery occurred in approximately 8% of cases for a variety of reasons including lap band adjustment, weight regain, gastric reflux problems, and rarely, because of staple-line leaks. Referring to findings based on the Bariatric Outcomes Longitudinal Database (BOLD), Dr. Popov said that mortality after primary bariatric surgery is estimated at around 0.2% and revisional procedures carry nearly the same low level of mortality risk. BOLD was developed by the American Society of Metabolic and Bariatric Surgery and reflects outcomes from certified Bariatric Centers of Excellence from 2007 to 2012. However, Dr. Popov noted, the outcomes derived from BOLD may well be better than those from noncertified centers (Gastrointest Surg. 2015 Jan;19[1]:171-8).

Dr. Popov reported that the number of revisional procedures has doubled over recent years, from 6% of all bariatric procedures in 2011 to 13% in 2015. The reasons behind the increase could be related to the number of patients switching to a different bariatric approach, the removal of lap bands, and possibly the increase in the number of primary bariatric surgeries performed by less-skilled operators, Dr. Popov said.

The investigators aimed to determine the mortality trends for these procedures in addition to evaluating costs and risk factors for complications. They conducted a retrospective cohort study using the 2014 NIS, comprising 14,280 patients who underwent revisional bariatric surgery. The primary outcome was postoperative in-hospital mortality, with secondary outcomes of cost, length of hospital stay (LOS), and ICU stay. The variables included a variety of comorbidities, alcohol use, smoking, income, and insurance status.

The mean age of this sample was 68 years and 58.8% were female. Outcomes for revisional bariatric surgery were worse in several categories than were found in the BOLD study in terms of LOS, costs, and mortality, and postoperative in-hospital mortality was unexpectedly high at 2.1% (290 patients). A total of 3.3% of the patients had an ICU stay, one-quarter of whom died.

On univariate analysis, comorbidities (age, coagulopathy, chronic kidney disease, anemia, and chronic heart failure) and the combined number of chronic conditions were all significant predictors of mortality. Multivariate analysis identified age (odds ratio, 1.08; 95% confidence interval, 1.04-1.20; P less than .001), alcohol use (OR, 4.0; 95% CI, 1.3-11.7; P = .01), coagulopathy (OR, 5.4; 95% CI, 2.2-13.3; P less than .001), and insurance status (Medicaid vs. private; OR, 4.0; 95% CI, 1.7-9.9; P = .002) as the most significant predictors of mortality after a revisional bariatric procedure.

tborden@mdedge.com

SOURCE: Popov VB et al. DDW 2018, Abstract 324.

WASHINGTON – Mortality after revisional bariatric procedures remains rare but may be more common than the literature suggests, and appears to be rising in recent years, according to two studies presented at the annual Digestive Disease Week^®.

Violeta B. Popov, MD, of New York University, and a team of researchers used the Nationwide Inpatient Sample (NIS) to look at mortality risk, costs, and risk factors for complications in revisional bariatric procedures.

In one presentation, Dr. Popov noted that revision after bariatric surgery occurred in approximately 8% of cases for a variety of reasons including lap band adjustment, weight regain, gastric reflux problems, and rarely, because of staple-line leaks. Referring to findings based on the Bariatric Outcomes Longitudinal Database (BOLD), Dr. Popov said that mortality after primary bariatric surgery is estimated at around 0.2% and revisional procedures carry nearly the same low level of mortality risk. BOLD was developed by the American Society of Metabolic and Bariatric Surgery and reflects outcomes from certified Bariatric Centers of Excellence from 2007 to 2012. However, Dr. Popov noted, the outcomes derived from BOLD may well be better than those from noncertified centers (Gastrointest Surg. 2015 Jan;19[1]:171-8).

Dr. Popov reported that the number of revisional procedures has doubled over recent years, from 6% of all bariatric procedures in 2011 to 13% in 2015. The reasons behind the increase could be related to the number of patients switching to a different bariatric approach, the removal of lap bands, and possibly the increase in the number of primary bariatric surgeries performed by less-skilled operators, Dr. Popov said.

The investigators aimed to determine the mortality trends for these procedures in addition to evaluating costs and risk factors for complications. They conducted a retrospective cohort study using the 2014 NIS, comprising 14,280 patients who underwent revisional bariatric surgery. The primary outcome was postoperative in-hospital mortality, with secondary outcomes of cost, length of hospital stay (LOS), and ICU stay. The variables included a variety of comorbidities, alcohol use, smoking, income, and insurance status.

The mean age of this sample was 68 years and 58.8% were female. Outcomes for revisional bariatric surgery were worse in several categories than were found in the BOLD study in terms of LOS, costs, and mortality, and postoperative in-hospital mortality was unexpectedly high at 2.1% (290 patients). A total of 3.3% of the patients had an ICU stay, one-quarter of whom died.

On univariate analysis, comorbidities (age, coagulopathy, chronic kidney disease, anemia, and chronic heart failure) and the combined number of chronic conditions were all significant predictors of mortality. Multivariate analysis identified age (odds ratio, 1.08; 95% confidence interval, 1.04-1.20; P less than .001), alcohol use (OR, 4.0; 95% CI, 1.3-11.7; P = .01), coagulopathy (OR, 5.4; 95% CI, 2.2-13.3; P less than .001), and insurance status (Medicaid vs. private; OR, 4.0; 95% CI, 1.7-9.9; P = .002) as the most significant predictors of mortality after a revisional bariatric procedure.

tborden@mdedge.com

SOURCE: Popov VB et al. DDW 2018, Abstract 324.

WASHINGTON – Mortality after revisional bariatric procedures remains rare but may be more common than the literature suggests, and appears to be rising in recent years, according to two studies presented at the annual Digestive Disease Week^®.

Violeta B. Popov, MD, of New York University, and a team of researchers used the Nationwide Inpatient Sample (NIS) to look at mortality risk, costs, and risk factors for complications in revisional bariatric procedures.

In one presentation, Dr. Popov noted that revision after bariatric surgery occurred in approximately 8% of cases for a variety of reasons including lap band adjustment, weight regain, gastric reflux problems, and rarely, because of staple-line leaks. Referring to findings based on the Bariatric Outcomes Longitudinal Database (BOLD), Dr. Popov said that mortality after primary bariatric surgery is estimated at around 0.2% and revisional procedures carry nearly the same low level of mortality risk. BOLD was developed by the American Society of Metabolic and Bariatric Surgery and reflects outcomes from certified Bariatric Centers of Excellence from 2007 to 2012. However, Dr. Popov noted, the outcomes derived from BOLD may well be better than those from noncertified centers (Gastrointest Surg. 2015 Jan;19[1]:171-8).

Dr. Popov reported that the number of revisional procedures has doubled over recent years, from 6% of all bariatric procedures in 2011 to 13% in 2015. The reasons behind the increase could be related to the number of patients switching to a different bariatric approach, the removal of lap bands, and possibly the increase in the number of primary bariatric surgeries performed by less-skilled operators, Dr. Popov said.

The investigators aimed to determine the mortality trends for these procedures in addition to evaluating costs and risk factors for complications. They conducted a retrospective cohort study using the 2014 NIS, comprising 14,280 patients who underwent revisional bariatric surgery. The primary outcome was postoperative in-hospital mortality, with secondary outcomes of cost, length of hospital stay (LOS), and ICU stay. The variables included a variety of comorbidities, alcohol use, smoking, income, and insurance status.

The mean age of this sample was 68 years and 58.8% were female. Outcomes for revisional bariatric surgery were worse in several categories than were found in the BOLD study in terms of LOS, costs, and mortality, and postoperative in-hospital mortality was unexpectedly high at 2.1% (290 patients). A total of 3.3% of the patients had an ICU stay, one-quarter of whom died.

On univariate analysis, comorbidities (age, coagulopathy, chronic kidney disease, anemia, and chronic heart failure) and the combined number of chronic conditions were all significant predictors of mortality. Multivariate analysis identified age (odds ratio, 1.08; 95% confidence interval, 1.04-1.20; P less than .001), alcohol use (OR, 4.0; 95% CI, 1.3-11.7; P = .01), coagulopathy (OR, 5.4; 95% CI, 2.2-13.3; P less than .001), and insurance status (Medicaid vs. private; OR, 4.0; 95% CI, 1.7-9.9; P = .002) as the most significant predictors of mortality after a revisional bariatric procedure.

tborden@mdedge.com

SOURCE: Popov VB et al. DDW 2018, Abstract 324.

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BOSTON – Though sleeve gastrectomy and Roux-en-Y gastric bypass are the bariatric procedures most patients will receive, other surgical approaches to weight loss are occasionally performed. Knowing these various techniques and their likely efficacy and safety can help physicians who care for patients with obesity, whether a patient is considering a less common option, or whether a post-vagal blockade patient shows up on the schedule with long-term issues.

A common theme among many of these procedures is that overall numbers are low, long-term follow-up may be lacking, and research quality is variable, said Travis McKenzie, MD, speaking at a bariatric surgery-focused session of the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists.

One minimally invasive approach targets stomach functions and the appetite and satiety signaling system. In vagal blockade via an electronic implant (vBloc), an indwelling, removable device produces electronically-induced intermittent blockade of the vagal nerve.

In one randomized controlled trial, excess weight loss in patients receiving this procedure was 24%, significantly more than the 16% seen in the group that received a sham procedure (P = .002); both groups received regular follow-up and counseling, according to the study protocol. Overall, at 1 year, 52% of those in the treatment group had seen at least 20% reduction in excess weight; just 3.7% of vBloc recipients had adverse events, mostly some dyspepsia and pain at the implant site, said Dr. McKenzie, an endocrine surgeon at the Mayo Clinic, Rochester, Minn.

The vBloc procedure, said Dr. McKenzie, “demonstrated modest weight loss at 2 years, with a reasonable risk profile.”

A variation of the duodenal switch is known as single anastomosis duodeno-ileal bypass with sleeve gastrectomy, or SADI-S. This procedure both resects the greater curve of the stomach to create a gastric sleeve, and uses a single intestinal anastomosis to create a common channel of 200, 250 or 300 cm, bypassing most of the small intestine.

In this procedure, also known as the one-anastomosis duodenal switch (OADS), weight loss occurs both because of intestinal malabsorption and because of the reduced stomach volume.

koakes@mdedge.com

SOURCE: McKenzie, T. AACE 2018, presentation SGS4.

BOSTON – Though sleeve gastrectomy and Roux-en-Y gastric bypass are the bariatric procedures most patients will receive, other surgical approaches to weight loss are occasionally performed. Knowing these various techniques and their likely efficacy and safety can help physicians who care for patients with obesity, whether a patient is considering a less common option, or whether a post-vagal blockade patient shows up on the schedule with long-term issues.

A common theme among many of these procedures is that overall numbers are low, long-term follow-up may be lacking, and research quality is variable, said Travis McKenzie, MD, speaking at a bariatric surgery-focused session of the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists.

One minimally invasive approach targets stomach functions and the appetite and satiety signaling system. In vagal blockade via an electronic implant (vBloc), an indwelling, removable device produces electronically-induced intermittent blockade of the vagal nerve.

In one randomized controlled trial, excess weight loss in patients receiving this procedure was 24%, significantly more than the 16% seen in the group that received a sham procedure (P = .002); both groups received regular follow-up and counseling, according to the study protocol. Overall, at 1 year, 52% of those in the treatment group had seen at least 20% reduction in excess weight; just 3.7% of vBloc recipients had adverse events, mostly some dyspepsia and pain at the implant site, said Dr. McKenzie, an endocrine surgeon at the Mayo Clinic, Rochester, Minn.

The vBloc procedure, said Dr. McKenzie, “demonstrated modest weight loss at 2 years, with a reasonable risk profile.”

A variation of the duodenal switch is known as single anastomosis duodeno-ileal bypass with sleeve gastrectomy, or SADI-S. This procedure both resects the greater curve of the stomach to create a gastric sleeve, and uses a single intestinal anastomosis to create a common channel of 200, 250 or 300 cm, bypassing most of the small intestine.

In this procedure, also known as the one-anastomosis duodenal switch (OADS), weight loss occurs both because of intestinal malabsorption and because of the reduced stomach volume.

koakes@mdedge.com

SOURCE: McKenzie, T. AACE 2018, presentation SGS4.

BOSTON – Though sleeve gastrectomy and Roux-en-Y gastric bypass are the bariatric procedures most patients will receive, other surgical approaches to weight loss are occasionally performed. Knowing these various techniques and their likely efficacy and safety can help physicians who care for patients with obesity, whether a patient is considering a less common option, or whether a post-vagal blockade patient shows up on the schedule with long-term issues.

A common theme among many of these procedures is that overall numbers are low, long-term follow-up may be lacking, and research quality is variable, said Travis McKenzie, MD, speaking at a bariatric surgery-focused session of the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists.

One minimally invasive approach targets stomach functions and the appetite and satiety signaling system. In vagal blockade via an electronic implant (vBloc), an indwelling, removable device produces electronically-induced intermittent blockade of the vagal nerve.

In one randomized controlled trial, excess weight loss in patients receiving this procedure was 24%, significantly more than the 16% seen in the group that received a sham procedure (P = .002); both groups received regular follow-up and counseling, according to the study protocol. Overall, at 1 year, 52% of those in the treatment group had seen at least 20% reduction in excess weight; just 3.7% of vBloc recipients had adverse events, mostly some dyspepsia and pain at the implant site, said Dr. McKenzie, an endocrine surgeon at the Mayo Clinic, Rochester, Minn.

The vBloc procedure, said Dr. McKenzie, “demonstrated modest weight loss at 2 years, with a reasonable risk profile.”

A variation of the duodenal switch is known as single anastomosis duodeno-ileal bypass with sleeve gastrectomy, or SADI-S. This procedure both resects the greater curve of the stomach to create a gastric sleeve, and uses a single intestinal anastomosis to create a common channel of 200, 250 or 300 cm, bypassing most of the small intestine.

In this procedure, also known as the one-anastomosis duodenal switch (OADS), weight loss occurs both because of intestinal malabsorption and because of the reduced stomach volume.

koakes@mdedge.com

SOURCE: McKenzie, T. AACE 2018, presentation SGS4.

BOSTON – For patients with obesity and metabolic syndrome or type 2 diabetes (T2D), it may be hard to best bariatric surgery for optimizing cardiovascular and metabolic health over the lifespan.

“Behavioral changes in diet and activity may be effective over the short term, but they are often ineffective over the long term,” said Daniel L. Hurley, MD. By contrast, “Bariatric surgery is very effective long-term,” he said.

At the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists, Dr. Hurley made the case for bariatric surgery in effective and durable management of type 2 diabetes and cardiovascular risk, weighing risks and benefits for those with higher and lower levels of obesity.

Speaking during a morning session focused on bariatric surgery, Dr. Hurley, an endocrionologist at the Mayo Clinic, Rochester, Minn., noted that bariatric surgery reduces not just weight, but also visceral adiposity. This, he said, is important when thinking about type 2 diabetes (T2D), because diabetes prevalence has climbed in the United States as obesity has also increased, according to examination of data from the National Health and Nutrition Examination Survey (NHANES).

Additionally, increased abdominal adiposity is associated with increased risk for cardiovascular-related deaths, myocardial infarctions, and all-cause deaths. Some of this relationship is mediated by T2D, which itself “is a major cause of cardiovascular-related morbidity and mortality,” said Dr. Hurley.

From a population health perspective, the increased prevalence of T2D – expected to reach 10% in the United States by 2030 – will also boost cardiovascular morbidity and mortality, said Dr. Hurley. Those with T2D die 5 to 10 years earlier, and have double the risk for heart attack and stroke of their peers without diabetes. The risk of lower limb amputation can be as much as 40 times greater for an individual with T2D across the lifespan, he said.

The National Institutes of Health recognizes bariatric surgery as an appropriate weight loss therapy for individuals with a body mass index (BMI) of at least 35 kg/m² and comorbidity. Whether bariatric surgery might be appropriate for individuals with T2D and BMIs of less than 35 kg/m² is less settled, though at least some RCTs support the surgical approach, said Dr. Hurley.

koakes@mdedge.com

SOURCE: Hurley, D. AACE 2018, Session SGS-4.

BOSTON – For patients with obesity and metabolic syndrome or type 2 diabetes (T2D), it may be hard to best bariatric surgery for optimizing cardiovascular and metabolic health over the lifespan.

“Behavioral changes in diet and activity may be effective over the short term, but they are often ineffective over the long term,” said Daniel L. Hurley, MD. By contrast, “Bariatric surgery is very effective long-term,” he said.

At the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists, Dr. Hurley made the case for bariatric surgery in effective and durable management of type 2 diabetes and cardiovascular risk, weighing risks and benefits for those with higher and lower levels of obesity.

Speaking during a morning session focused on bariatric surgery, Dr. Hurley, an endocrionologist at the Mayo Clinic, Rochester, Minn., noted that bariatric surgery reduces not just weight, but also visceral adiposity. This, he said, is important when thinking about type 2 diabetes (T2D), because diabetes prevalence has climbed in the United States as obesity has also increased, according to examination of data from the National Health and Nutrition Examination Survey (NHANES).

Additionally, increased abdominal adiposity is associated with increased risk for cardiovascular-related deaths, myocardial infarctions, and all-cause deaths. Some of this relationship is mediated by T2D, which itself “is a major cause of cardiovascular-related morbidity and mortality,” said Dr. Hurley.

From a population health perspective, the increased prevalence of T2D – expected to reach 10% in the United States by 2030 – will also boost cardiovascular morbidity and mortality, said Dr. Hurley. Those with T2D die 5 to 10 years earlier, and have double the risk for heart attack and stroke of their peers without diabetes. The risk of lower limb amputation can be as much as 40 times greater for an individual with T2D across the lifespan, he said.

The National Institutes of Health recognizes bariatric surgery as an appropriate weight loss therapy for individuals with a body mass index (BMI) of at least 35 kg/m² and comorbidity. Whether bariatric surgery might be appropriate for individuals with T2D and BMIs of less than 35 kg/m² is less settled, though at least some RCTs support the surgical approach, said Dr. Hurley.

koakes@mdedge.com

SOURCE: Hurley, D. AACE 2018, Session SGS-4.

BOSTON – For patients with obesity and metabolic syndrome or type 2 diabetes (T2D), it may be hard to best bariatric surgery for optimizing cardiovascular and metabolic health over the lifespan.

“Behavioral changes in diet and activity may be effective over the short term, but they are often ineffective over the long term,” said Daniel L. Hurley, MD. By contrast, “Bariatric surgery is very effective long-term,” he said.

At the annual clinical and scientific meeting of the American Association of Clinical Endocrinologists, Dr. Hurley made the case for bariatric surgery in effective and durable management of type 2 diabetes and cardiovascular risk, weighing risks and benefits for those with higher and lower levels of obesity.

Speaking during a morning session focused on bariatric surgery, Dr. Hurley, an endocrionologist at the Mayo Clinic, Rochester, Minn., noted that bariatric surgery reduces not just weight, but also visceral adiposity. This, he said, is important when thinking about type 2 diabetes (T2D), because diabetes prevalence has climbed in the United States as obesity has also increased, according to examination of data from the National Health and Nutrition Examination Survey (NHANES).

Additionally, increased abdominal adiposity is associated with increased risk for cardiovascular-related deaths, myocardial infarctions, and all-cause deaths. Some of this relationship is mediated by T2D, which itself “is a major cause of cardiovascular-related morbidity and mortality,” said Dr. Hurley.

From a population health perspective, the increased prevalence of T2D – expected to reach 10% in the United States by 2030 – will also boost cardiovascular morbidity and mortality, said Dr. Hurley. Those with T2D die 5 to 10 years earlier, and have double the risk for heart attack and stroke of their peers without diabetes. The risk of lower limb amputation can be as much as 40 times greater for an individual with T2D across the lifespan, he said.

The National Institutes of Health recognizes bariatric surgery as an appropriate weight loss therapy for individuals with a body mass index (BMI) of at least 35 kg/m² and comorbidity. Whether bariatric surgery might be appropriate for individuals with T2D and BMIs of less than 35 kg/m² is less settled, though at least some RCTs support the surgical approach, said Dr. Hurley.

koakes@mdedge.com

SOURCE: Hurley, D. AACE 2018, Session SGS-4.

For people with diabetes, disease management can become a part-time job that affects their actual jobs, their sleep, their relationships, and their recreational activities, according to a new survey by prescription manager UpWell Health.

The time spent on activities that come with diabetes management – blood glucose monitoring, diet planning, medical appointments – can add up to several hours a week. Among the 5,255 respondents to the online survey, 18% said that such tasks took up 5-10 hours each week, 7% said it was 10-15 hours, and 9% said they spent 15 or more hours a week on diabetes-related tasks, UpWell reported.

rfranki@mdedge.com

For people with diabetes, disease management can become a part-time job that affects their actual jobs, their sleep, their relationships, and their recreational activities, according to a new survey by prescription manager UpWell Health.

The time spent on activities that come with diabetes management – blood glucose monitoring, diet planning, medical appointments – can add up to several hours a week. Among the 5,255 respondents to the online survey, 18% said that such tasks took up 5-10 hours each week, 7% said it was 10-15 hours, and 9% said they spent 15 or more hours a week on diabetes-related tasks, UpWell reported.

rfranki@mdedge.com

For people with diabetes, disease management can become a part-time job that affects their actual jobs, their sleep, their relationships, and their recreational activities, according to a new survey by prescription manager UpWell Health.

The time spent on activities that come with diabetes management – blood glucose monitoring, diet planning, medical appointments – can add up to several hours a week. Among the 5,255 respondents to the online survey, 18% said that such tasks took up 5-10 hours each week, 7% said it was 10-15 hours, and 9% said they spent 15 or more hours a week on diabetes-related tasks, UpWell reported.

rfranki@mdedge.com

A total of 12 deaths over the past 2 years have been linked to the use of liquid-filled intragastric balloon devices for the treatment of obesity, according to an alert from the Food and Drug Administration issued on June 4.

Seven of these deaths occurred in patients in the United States; four involved the ORBERA Intragastric Balloon System, and three involved the ReShape Integrated Dual Balloon System.

A total of 12 deaths over the past 2 years have been linked to the use of liquid-filled intragastric balloon devices for the treatment of obesity, according to an alert from the Food and Drug Administration issued on June 4.

Seven of these deaths occurred in patients in the United States; four involved the ORBERA Intragastric Balloon System, and three involved the ReShape Integrated Dual Balloon System.

A total of 12 deaths over the past 2 years have been linked to the use of liquid-filled intragastric balloon devices for the treatment of obesity, according to an alert from the Food and Drug Administration issued on June 4.

Seven of these deaths occurred in patients in the United States; four involved the ORBERA Intragastric Balloon System, and three involved the ReShape Integrated Dual Balloon System.

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

koakes@mdedge.com

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

koakes@mdedge.com

BOSTON – Evidence from a twin study points to genes, rather than just adiposity, as the underlying factor in differences in appetite and satiety that have been observed in obesity.

The work adds a new dimension – and some questions – to previous research, which suggested individuals with obesity show heightened brain activation to food cues, especially calorically dense food.

“We thought it was fat mass…but when we controlled for everything that monozygotic pairs have in common, that relationship went away, implicating something that the monozygotic twins have in common, i.e., genetics,” said first author Jennifer Rosenbaum, MD, in a video interview at the annual meeting of the American Academy of Clinical Endocrinologists.

Dr. Rosenbaum, a fellow in the department of metabolism, endocrinology, and nutrition at the University of Washington, Seattle, and her collaborators made use of a statewide twin registry to conduct an extensive investigation of subjective and objective measures of appetite and satiety in the 42 twin pairs.

Twins had a mean age of 31 years; 27 of the twin pairs were monozygotic, Dr. Rosenbaum said. At least one member of each twin pair met criteria for obesity, and participants had a mean body mass index of 32.8 kg/m².

On the study day, participants arrived in fasting state, and had a fixed-calorie breakfast equivalent to 10% of their daily caloric needs. They then underwent dual-energy x-ray absorptiometry scanning to determine adiposity, and also filled out a behavioral questionnaire.

Then, participants received the first of two functional MRI scans; during the scan, they were shown images of high calorie foods, low calorie foods, and nonfood objects, completing ratings of how appealing they found each image. After consuming another standardized meal equivalent to 20% of daily caloric needs, the fMRI scan was repeated.

Finally, participants were given access to a buffet meal and allowed to eat as much as they chose; consumption was measured. Before and after each meal and scan, and at various points during the day, the investigators also obtained blood samples and asked participants to rate their hunger on a visual analog scale.

“When compared with how much fat mass they had, there was no relationship between how hungry or full they were when they were fasting, how hungry or full they were with a snack, or when they ate the buffet. It just didn’t matter how much fat mass they had” for subjective reporting of hunger and fullness, said Dr. Rosenbaum.

However, there was a direct correlation between fat mass and amount consumed at the ad libitum buffet. Additionally, the fMRI analysis showed that “the brain activation that we would expect to go down, didn’t seem to go down as much if you had more adiposity,” she said.

As fat mass went up, areas of the brain implicated in appetite and reward showed more activity when participants were presented with the tempting images of high calorie foods, regardless of the calories consumed. These areas include the ventral and dorsal striata, the amygdala, the insula, the ventral tegmental area, and the medial orbitofrontal cortex.

Next, the researchers looked for differences within the monozygotic twin pairs, who essentially share a genome. They compared the brain activation of the twin with the higher fat mass with that of the twin with lower fat mass. Instead of seeing the same correlation between higher adiposity and greater brain activation with tempting stimuli, “Suddenly, we lost that relationship between how many calories they would eat and how their brain activated with the food,” said Dr. Rosenbaum. This is a clue, she said, that genetics, rather than simple adiposity, is driving the different responses to food cues.

The study was funded by the National Institutes of Health. Dr. Rosenbaum reported no financial disclosures.

koakes@mdedge.com

Patients with type 2 diabetes had lower levels of a bone formation marker after treatment with metformin in a Danish clinical trial.

Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.

By contrast, insulin did not appear to influence markers of bone turnover.

Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.

These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.

Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.

Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.

Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.

Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.

HbA_1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.

“Further clinical trials investigating the effects of improved glycemic control on bone remodeling including other biochemical markers of bone turnover are needed to confirm if lowering of glucose levels solely changes bone resorption and not formation,” Dr. Stage and his coauthors wrote.

This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.

SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.

Patients with type 2 diabetes had lower levels of a bone formation marker after treatment with metformin in a Danish clinical trial.

Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.

By contrast, insulin did not appear to influence markers of bone turnover.

Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.

These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.

Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.

Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.

Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.

Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.

HbA_1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.

“Further clinical trials investigating the effects of improved glycemic control on bone remodeling including other biochemical markers of bone turnover are needed to confirm if lowering of glucose levels solely changes bone resorption and not formation,” Dr. Stage and his coauthors wrote.

This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.

SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.

Patients with type 2 diabetes had lower levels of a bone formation marker after treatment with metformin in a Danish clinical trial.

Procollagen type 1 N-terminal peptide (P1NP) plasma concentrations were lower in patients who received either metformin or metformin plus rosiglitazone, Tore Bjerregaard Stage, PhD, a specialist in clinical pharmacology and pharmacy at the University of Southern Denmark, Odense, and his coauthors wrote in Bone.

By contrast, insulin did not appear to influence markers of bone turnover.

Improving glycemic control was associated with increased plasma concentrations of C-terminal telopeptide of collagen (CTx), a marker of bone resorption. However, this finding might reflect “normalization, rather than an abnormal increase in bone resorption,” Dr. Stage and his colleagues wrote.

These findings come from an analysis of the South Danish Diabetes Study, a 2-year, multicenter, randomized, controlled trial including 371 patients with type 2 diabetes. Patients were first randomized to receive short- or long-acting human insulin, then further randomized to metformin plus rosiglitazone, metformin plus placebo, rosiglitazone plus placebo, or two placebos.

Bone turnover markers were assessed at baseline and at 3-, 12-, and 24-month follow-ups.

Dr. Stage and his coinvestigators hoped the analysis would provide insights into how antidiabetic medication might influence bone turnover, potentially helping explain the increased risk of fracture found in patients with type 2 diabetes. “Alterations in bone metabolism due to antidiabetic medication may influence bone metabolism both directly, e.g., by insulin promoting bone formation, and indirectly by improvement of glycemic control,” they wrote.

Overall, levels of both bone turnover markers increased over time in the study. However, investigators found that concentrations of the bone formation marker P1NP were 13% lower in patients randomized to metformin alone, and 21% lower in patients randomized to metformin and rosiglitazone; no such association was found between P1NP concentrations and treatment with rosiglitazone alone. By contrast, the type of oral antidiabetic drug treatment had no effect on concentrations of CTx concentrations, the investigators said.

Type of insulin treatment received in the trial did not appear to have an impact on concentrations of either bone turnover marker, they added.

HbA_1c had no influence on concentrations of P1NP; but it was inversely correlated with levels of CTx, a finding that the investigators said merits more study.

“Further clinical trials investigating the effects of improved glycemic control on bone remodeling including other biochemical markers of bone turnover are needed to confirm if lowering of glucose levels solely changes bone resorption and not formation,” Dr. Stage and his coauthors wrote.

This study was funded with grants from the Danish Council for Independent Research and the Region of Southern Denmark. Dr. Stage and coauthors reported no conflicts of interest related to the report.

SOURCE: Stage TB et al. Bone. 2018 Apr 12;112:35-41.

AUSTIN, TEX. – Canagliflozin can improve renal outcomes in patients with type 2 diabetes, even when they have mild or moderate kidney disease, new data from the CANVAS program suggested.

“The effect of canagliflozin on composite renal outcomes was large, particularly in people with preserved kidney function,” Brendon L. Neuen, MBBS, of University of New South Wales, Sydney, and his associates wrote in a poster. Baseline renal function also did not appear to affect the safety of canagliflozin, the investigators reported at a meeting sponsored by the National Kidney Foundation.

In patients with diabetes mellitus, increased proximal reabsorption of glucose and sodium decreases the amount of sodium reaching the macula densa in the distal convoluted tubule. This results in reduced use of adenosine triphosphate for sodium reabsorption, which thereby decreases adenosine release and vasoconstriction of afferent arterioles. Left unchecked, this dampening of the tubuloglomerular feedback mechanism increases glomerular filtration and leads to diabetic nephropathy.

Sodium glucose cotransporter 2 (SGLT2) inhibitors such as canagliflozin (Invokana) and empagliflozin (Jardiance) help mitigate this pathology by vasoconstricting afferent arterioles. Previously, in an exploratory analysis of the multicenter, placebo-controlled EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial, empagliflozin led to modest but statistically significant long-term reductions in urinary albumin secretion for diabetic patients, regardless of their baseline urinary albumin to creatinine ratio (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). Treatment with empagliflozin also significantly reduced the risk of developing microalbuminuria or macroalbuminuria (P less than .0001).

The multicenter, double-blind, placebo-controlled CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) trials included more than 10,000 adults with type 2 diabetes and high cardiovascular risk. In the primary analysis, canagliflozin significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo (N Engl J Med. 2017 Aug 17;377[7]:644-57).

Dr. Neuen and his associates compared the effects of canagliflozin on renal outcomes and safety among CANVAS patients whose estimated glomerular filtration rate (eGFR) was preserved (greater than 60 mL/min per 1.73 m²) or reduced (less than 60 ml/min per 1.73 m²). Actual mean eGFRs in each of these groups were 83 mL/min per 1.73 m² and 49 mL/min per 1.73 m², respectively. Compared with placebo, canagliflozin acutely reduced eGFR in patients with either preserved (average, –2.2 mL/min per 1.73 m²) or reduced (–2.83 mL/min/1.73 m² ) baseline kidney function (P = 0.21).

SOURCE: Neuen BL et al. SCM 2018.
 

AUSTIN, TEX. – Canagliflozin can improve renal outcomes in patients with type 2 diabetes, even when they have mild or moderate kidney disease, new data from the CANVAS program suggested.

“The effect of canagliflozin on composite renal outcomes was large, particularly in people with preserved kidney function,” Brendon L. Neuen, MBBS, of University of New South Wales, Sydney, and his associates wrote in a poster. Baseline renal function also did not appear to affect the safety of canagliflozin, the investigators reported at a meeting sponsored by the National Kidney Foundation.

In patients with diabetes mellitus, increased proximal reabsorption of glucose and sodium decreases the amount of sodium reaching the macula densa in the distal convoluted tubule. This results in reduced use of adenosine triphosphate for sodium reabsorption, which thereby decreases adenosine release and vasoconstriction of afferent arterioles. Left unchecked, this dampening of the tubuloglomerular feedback mechanism increases glomerular filtration and leads to diabetic nephropathy.

Sodium glucose cotransporter 2 (SGLT2) inhibitors such as canagliflozin (Invokana) and empagliflozin (Jardiance) help mitigate this pathology by vasoconstricting afferent arterioles. Previously, in an exploratory analysis of the multicenter, placebo-controlled EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial, empagliflozin led to modest but statistically significant long-term reductions in urinary albumin secretion for diabetic patients, regardless of their baseline urinary albumin to creatinine ratio (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). Treatment with empagliflozin also significantly reduced the risk of developing microalbuminuria or macroalbuminuria (P less than .0001).

The multicenter, double-blind, placebo-controlled CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) trials included more than 10,000 adults with type 2 diabetes and high cardiovascular risk. In the primary analysis, canagliflozin significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo (N Engl J Med. 2017 Aug 17;377[7]:644-57).

Dr. Neuen and his associates compared the effects of canagliflozin on renal outcomes and safety among CANVAS patients whose estimated glomerular filtration rate (eGFR) was preserved (greater than 60 mL/min per 1.73 m²) or reduced (less than 60 ml/min per 1.73 m²). Actual mean eGFRs in each of these groups were 83 mL/min per 1.73 m² and 49 mL/min per 1.73 m², respectively. Compared with placebo, canagliflozin acutely reduced eGFR in patients with either preserved (average, –2.2 mL/min per 1.73 m²) or reduced (–2.83 mL/min/1.73 m² ) baseline kidney function (P = 0.21).

SOURCE: Neuen BL et al. SCM 2018.
 

AUSTIN, TEX. – Canagliflozin can improve renal outcomes in patients with type 2 diabetes, even when they have mild or moderate kidney disease, new data from the CANVAS program suggested.

“The effect of canagliflozin on composite renal outcomes was large, particularly in people with preserved kidney function,” Brendon L. Neuen, MBBS, of University of New South Wales, Sydney, and his associates wrote in a poster. Baseline renal function also did not appear to affect the safety of canagliflozin, the investigators reported at a meeting sponsored by the National Kidney Foundation.

In patients with diabetes mellitus, increased proximal reabsorption of glucose and sodium decreases the amount of sodium reaching the macula densa in the distal convoluted tubule. This results in reduced use of adenosine triphosphate for sodium reabsorption, which thereby decreases adenosine release and vasoconstriction of afferent arterioles. Left unchecked, this dampening of the tubuloglomerular feedback mechanism increases glomerular filtration and leads to diabetic nephropathy.

Sodium glucose cotransporter 2 (SGLT2) inhibitors such as canagliflozin (Invokana) and empagliflozin (Jardiance) help mitigate this pathology by vasoconstricting afferent arterioles. Previously, in an exploratory analysis of the multicenter, placebo-controlled EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial, empagliflozin led to modest but statistically significant long-term reductions in urinary albumin secretion for diabetic patients, regardless of their baseline urinary albumin to creatinine ratio (Lancet Diabetes Endocrinol. 2017 Aug;5[8]:610-21). Treatment with empagliflozin also significantly reduced the risk of developing microalbuminuria or macroalbuminuria (P less than .0001).

The multicenter, double-blind, placebo-controlled CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus) trials included more than 10,000 adults with type 2 diabetes and high cardiovascular risk. In the primary analysis, canagliflozin significantly reduced the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo (N Engl J Med. 2017 Aug 17;377[7]:644-57).

Dr. Neuen and his associates compared the effects of canagliflozin on renal outcomes and safety among CANVAS patients whose estimated glomerular filtration rate (eGFR) was preserved (greater than 60 mL/min per 1.73 m²) or reduced (less than 60 ml/min per 1.73 m²). Actual mean eGFRs in each of these groups were 83 mL/min per 1.73 m² and 49 mL/min per 1.73 m², respectively. Compared with placebo, canagliflozin acutely reduced eGFR in patients with either preserved (average, –2.2 mL/min per 1.73 m²) or reduced (–2.83 mL/min/1.73 m² ) baseline kidney function (P = 0.21).

SOURCE: Neuen BL et al. SCM 2018.