Endocrinology

TOPLINE:

The prevalence of diabetes in the United States increased by 18.6% from 2012 to 2022, with notably higher rates among racial and ethnic minorities, men, older adults, and socioeconomically disadvantaged populations.

METHODOLOGY:

• Over 37 million people in the United States have diabetes, and its prevalence is only expected to increase in the coming years, making identifying high-risk demographic groups particularly crucial.
• To assess recent national trends and disparities in diabetes prevalence among US adults, researchers conducted an observational study using data from the Behavioral Risk Factor Surveillance System and included 5,312,827 observations from 2012 to 2022.
• Diabetes was defined on the basis of a previous self-reported diagnosis using standardized questionnaires.
• The sociodemographic factors of age, sex, race, education, physical activity, income, and body mass index were used to establish the risk indicators for diabetes diagnosis.
• Age-standardized diabetes prevalence and the association between risk factors and diabetes were assessed both overall and across various sociodemographic groups.

TAKEAWAY:

• The overall prevalence of diabetes increased by 18.6% (P < .001) from 2012 to 2022, with the highest prevalence observed among non-Hispanic Black individuals (15.8%) and people aged ≥ 65 years (23.86%).
• The likelihood of being diagnosed with diabetes was 1.15 times higher in men than in women, 5.16 times higher in adults aged 45-64 years than in those aged 18-24 years, and 3.64 times higher in those with obesity than in those with normal weight.
• The risk for being diagnosed with diabetes was 1.60 times higher among Hispanic individuals, 1.67 times higher among non-Hispanic Asian individuals, and 2.10 times higher among non-Hispanic Black individuals than among non-Hispanic White individuals.
• Individuals with a college education and higher income level were 24% and 41% less likely, respectively, to be diagnosed with diabetes.

IN PRACTICE:

“Improving access to quality care, implementing diabetes prevention programs focusing on high-risk groups, and addressing social determinants through multilevel interventions may help curb the diabetes epidemic in the United States,” the authors wrote.

SOURCE:

The study, led by Sulakshan Neupane, MS, Department of Agricultural and Applied Economics, University of Georgia, Athens, Georgia, was published online in Diabetes, Obesity, and Metabolism.

LIMITATIONS:

The self-reported diagnoses and lack of clinical data may have introduced bias. Diabetes prevalence could not be analyzed in South-East Asian and South Asian populations owing to limitations in the data collection process.

DISCLOSURES:

The study was not supported by any funding, and no potential author disclosures or conflicts were identified.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The prevalence of diabetes in the United States increased by 18.6% from 2012 to 2022, with notably higher rates among racial and ethnic minorities, men, older adults, and socioeconomically disadvantaged populations.

METHODOLOGY:

• Over 37 million people in the United States have diabetes, and its prevalence is only expected to increase in the coming years, making identifying high-risk demographic groups particularly crucial.
• To assess recent national trends and disparities in diabetes prevalence among US adults, researchers conducted an observational study using data from the Behavioral Risk Factor Surveillance System and included 5,312,827 observations from 2012 to 2022.
• Diabetes was defined on the basis of a previous self-reported diagnosis using standardized questionnaires.
• The sociodemographic factors of age, sex, race, education, physical activity, income, and body mass index were used to establish the risk indicators for diabetes diagnosis.
• Age-standardized diabetes prevalence and the association between risk factors and diabetes were assessed both overall and across various sociodemographic groups.

TAKEAWAY:

• The overall prevalence of diabetes increased by 18.6% (P < .001) from 2012 to 2022, with the highest prevalence observed among non-Hispanic Black individuals (15.8%) and people aged ≥ 65 years (23.86%).
• The likelihood of being diagnosed with diabetes was 1.15 times higher in men than in women, 5.16 times higher in adults aged 45-64 years than in those aged 18-24 years, and 3.64 times higher in those with obesity than in those with normal weight.
• The risk for being diagnosed with diabetes was 1.60 times higher among Hispanic individuals, 1.67 times higher among non-Hispanic Asian individuals, and 2.10 times higher among non-Hispanic Black individuals than among non-Hispanic White individuals.
• Individuals with a college education and higher income level were 24% and 41% less likely, respectively, to be diagnosed with diabetes.

IN PRACTICE:

“Improving access to quality care, implementing diabetes prevention programs focusing on high-risk groups, and addressing social determinants through multilevel interventions may help curb the diabetes epidemic in the United States,” the authors wrote.

SOURCE:

The study, led by Sulakshan Neupane, MS, Department of Agricultural and Applied Economics, University of Georgia, Athens, Georgia, was published online in Diabetes, Obesity, and Metabolism.

LIMITATIONS:

The self-reported diagnoses and lack of clinical data may have introduced bias. Diabetes prevalence could not be analyzed in South-East Asian and South Asian populations owing to limitations in the data collection process.

DISCLOSURES:

The study was not supported by any funding, and no potential author disclosures or conflicts were identified.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The prevalence of diabetes in the United States increased by 18.6% from 2012 to 2022, with notably higher rates among racial and ethnic minorities, men, older adults, and socioeconomically disadvantaged populations.

METHODOLOGY:

• Over 37 million people in the United States have diabetes, and its prevalence is only expected to increase in the coming years, making identifying high-risk demographic groups particularly crucial.
• To assess recent national trends and disparities in diabetes prevalence among US adults, researchers conducted an observational study using data from the Behavioral Risk Factor Surveillance System and included 5,312,827 observations from 2012 to 2022.
• Diabetes was defined on the basis of a previous self-reported diagnosis using standardized questionnaires.
• The sociodemographic factors of age, sex, race, education, physical activity, income, and body mass index were used to establish the risk indicators for diabetes diagnosis.
• Age-standardized diabetes prevalence and the association between risk factors and diabetes were assessed both overall and across various sociodemographic groups.

TAKEAWAY:

• The overall prevalence of diabetes increased by 18.6% (P < .001) from 2012 to 2022, with the highest prevalence observed among non-Hispanic Black individuals (15.8%) and people aged ≥ 65 years (23.86%).
• The likelihood of being diagnosed with diabetes was 1.15 times higher in men than in women, 5.16 times higher in adults aged 45-64 years than in those aged 18-24 years, and 3.64 times higher in those with obesity than in those with normal weight.
• The risk for being diagnosed with diabetes was 1.60 times higher among Hispanic individuals, 1.67 times higher among non-Hispanic Asian individuals, and 2.10 times higher among non-Hispanic Black individuals than among non-Hispanic White individuals.
• Individuals with a college education and higher income level were 24% and 41% less likely, respectively, to be diagnosed with diabetes.

IN PRACTICE:

“Improving access to quality care, implementing diabetes prevention programs focusing on high-risk groups, and addressing social determinants through multilevel interventions may help curb the diabetes epidemic in the United States,” the authors wrote.

SOURCE:

The study, led by Sulakshan Neupane, MS, Department of Agricultural and Applied Economics, University of Georgia, Athens, Georgia, was published online in Diabetes, Obesity, and Metabolism.

LIMITATIONS:

The self-reported diagnoses and lack of clinical data may have introduced bias. Diabetes prevalence could not be analyzed in South-East Asian and South Asian populations owing to limitations in the data collection process.

DISCLOSURES:

The study was not supported by any funding, and no potential author disclosures or conflicts were identified.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

If you’re like most primary care clinicians, your email inbox is flooded with messages from patients with questions about lab results. A common query: Should I be worried about an abnormal value on a test of thyroid-stimulating hormone (TSH)?

For guidance, this news organization spoke with Angela Leung, MD, associate professor of medicine in the Division of Endocrinology, Diabetes & Metabolism at the UCLA David Geffen School of Medicine and an endocrinologist at UCLA and the VA Greater Los Angeles Healthcare System, and Karen Tsai, MD, assistant clinical professor of endocrinology at City of Hope Comprehensive Cancer Center in Duarte, California. The following interview has been edited for length and clarity.

Question: Why do you usually start by measuring TSH levels?

Dr. Leung: We need to measure the thyroid status in a way that integrates more information about the long-term thyroid status and not small changes in thyroid hormone levels. TSH is made by the pituitary gland in the brain, which integrates information about the signals of high and low levels from each of the different thyroid hormones.

Now we can measure the actual thyroid hormones — primarily we’re talking about T3 and T4 — but if we do that, we are relying on a single snapshot in the bloodstream at that moment. The levels might change throughout the day in response to ongoing metabolism and outside stresses. So we usually start by measuring the TSH level, which is a good representation of the compilation of all those things over the past 30 days or so.

Question: How do you describe a low TSH result to patients?

Dr. Leung: Whenever we encounter a low TSH level, we want to repeat the test because it is a dynamic test, and it can change in response to several factors. If it is indeed low, we’re thinking that perhaps there’s a little bit of extra thyroid hormone in the body. It can be either temporary or more chronic, but that higher amount of thyroid hormone is telling the pituitary gland in the brain to start making less. So TSH levels go low when we need less thyroid hormone.

Question: What are some of the reasons for a low TSH level?

Dr. Leung: One of the most common situations for a temporarily low TSH level I see is what we call nonthyroidal illness, like a common cold or just being under the weather. Other things that can artifactually lower the TSH level could be the use of steroids, such as prednisone for asthma or some sort of a rheumatologic condition. Also, the TSH level could be low if a person has been recently exposed to very high amounts of iodine, such as iodinated contrast needed for a CT scan.

If the TSH level remains persistently low, usually in the presence of high thyroid hormone (T3 and/or T4) levels, the most common reason for hyperthyroidism is Graves disease, in which there are autoantibodies — measurable in the blood — that can stimulate the thyroid gland in the neck to make extra thyroid hormone.

Question: And what does an elevated TSH level mean?

Dr. Leung: Again, we want to confirm that it is elevated. We need at least two tests to confirm a high TSH level. A persistently elevated TSH level is a signal there might be low thyroid hormone levels in the body, which could be transient or more longer lasting.

Question: What are some of the most common causes of an elevated TSH level?

Dr. Leung: If the TSH level is confirmed high and the thyroid hormone levels are low, the most common cause of hypothyroidism here in the United States is Hashimoto thyroiditis.

Globally, iodine deficiency is the most common reason for hypothyroidism and may be a problem in parts of the globe where there are endemically low iodine levels in soil, crops, and the food supply like not having enough iodized salt. The thyroid is reliant on having enough iodine as a micronutrient to make thyroid hormone. If it doesn’t, the thyroid really can’t make thyroid hormone. It’s important to also remember, though, that having too much iodine can result in hypo- or hyperthyroidism.

Dr. Tsai: I take a glance at their medication list. Some of the patients are on methimazole or levothyroxine, and those medications should be adjusted first to normalize the TSH level. Other medications like lithium and amiodarone can also cause elevated TSH levels. We are also seeing a lot of patients on cancer therapies, such as tyrosine kinase inhibitors or immunotherapy, that can cause an elevated TSH level.

Question: If the repeat TSH test shows that TSH levels are still elevated, what comes next in your workup?

Dr. Tsai: If there’s not a real clear-cut diagnosis, I’ll order the thyroid peroxidase antibody and the thyroglobulin antibody, although thyroid peroxidase antibody, which is indicative of autoimmune thyroid disease, alone is usually sufficient to make that diagnosis.

Question: Should clinicians follow thyroid antibodies over time?

Dr. Tsai: I usually don’t repeat the antibody tests. In those circumstances where patients who were diagnosed 50-60 years ago and perhaps it is unknown if they had the thyroid antibodies measured at the time and now they’re saying, “Do I actually have Hashimoto’s?” or “Do I really need to continue this for the rest of my life?” I do repeat antibody tests to help gauge if the patient’s levothyroxine can be stopped.

Question: How important is it to follow T4 or T3 levels?

Dr. Tsai: T4 and T3 levels can help differentiate overt thyroid dysfunction — where T3 and/or T4 levels will be abnormal — from subclinical thyroid dysfunction — where T3 and T4 levels would be normal. In general, although we do not fully appreciate the best metric to monitor hypo- or hyperthyroidism, because some patients with a normal TSH level still may have symptoms of thyroid dysfunction, these peripheral thyroid hormone levels are usually the most helpful at the time of initial diagnosis.

Question: What are your criteria for initiating treatment for hypothyroidism?

Dr. Tsai: If the TSH level > 10 mIU/L, I recommend levothyroxine hormone replacement. A lot of published data support clinical benefit in this group.

There is a gray area in those patients who have a TSH level higher than the upper limit of the reference range but less than 10. If the patient doesn’t have overt hypothyroid symptoms, I discuss the findings with the patient but don’t really feel eager to treat. I recommend checking the levels again in 6 months to see where that TSH goes, and if it worsens or becomes greater than 10 mIU/L, I then recommend levothyroxine hormone replacement.

It is also important to note that a TSH level of 5-7 may be an acceptable range for older patients, and they do not require levothyroxine.

The other category is patients whose TSH level is greater than the upper limit of the normal reference range but less than 10 and with overt hypothyroid symptoms such as fatigue, unintentional weight gain, constipation, or cold intolerance. In these patients, it is worthwhile to try a low dose of levothyroxine (25-50 mcg/d) and repeat TSH and free T4 tests in 6-8 weeks and see if the TSH level normalizes.

Dr. Leung: When you look at subclinical hypothyroidism, the situation of an isolated high TSH level in the setting of normal T4 levels, if the TSH level is mildly elevated in the 5-7 mIU/L range, there’s a 60% chance that it will normalize within 6 months.

Going back to Karen’s point, a lot of people are started and maintained on low doses of thyroid hormone forever and ever. A recent study on levothyroxine use found half of the prescriptions were unnecessary.

Question: In an era where many patients obtain much of their health information from TikTok, what’s your approach with patients with a normal TSH level who feel that they should have more testing or start treatment?

Dr. Tsai: Fatigue is one of the common referrals we get into our endocrinology practice, and everyone is convinced that their thyroid is the culprit. It is important to note, however, that fatigue can be due to different diseases such as anemia, depression, sleep disorders, or a recent viral illness.

TSH tests are readily available and cheap. I don’t mind ordering the lab test again if it helps give the patient some reassurance. I also find that patients are relieved once they hear from their endocrinologist that their thyroid is unlikely to be the cause of their fatigue.

Some other endocrine causes we may consider additionally working up include adrenal insufficiency, vitamin D deficiency, and diabetes. A comprehensive metabolic panel and complete blood count is part of my workup to rule out any gross electrolyte abnormalities or any new diagnosis of anemia, liver disease, or chronic kidney disease.

Question: What are your criteria for recommending that someone see an endocrinologist?

Dr. Tsai: Our primary care colleagues can do a workup and interpretation of thyroid function tests in most cases. In the situations where the thyroid function test results are discordant (ie, elevated TSH and elevated free T4 levels or low TSH and low free T4 levels) or difficult to interpret, it would be appropriate to refer the patient to an endocrinologist.

One of the common referrals that we do get from the community is a patient’s thyroid function tests going from hyperthyroid to hypothyroid without a clear explanation or the patient is suboptimally controlled with levothyroxine or methimazole. In those circumstances, it would be worthwhile to send to an endocrinologist try to discern an underlying cause or for optimization of medication.

Dr. Leung and Dr. Tsai had no financial disclosures.
 

A version of this article appeared on Medscape.com.

If you’re like most primary care clinicians, your email inbox is flooded with messages from patients with questions about lab results. A common query: Should I be worried about an abnormal value on a test of thyroid-stimulating hormone (TSH)?

For guidance, this news organization spoke with Angela Leung, MD, associate professor of medicine in the Division of Endocrinology, Diabetes & Metabolism at the UCLA David Geffen School of Medicine and an endocrinologist at UCLA and the VA Greater Los Angeles Healthcare System, and Karen Tsai, MD, assistant clinical professor of endocrinology at City of Hope Comprehensive Cancer Center in Duarte, California. The following interview has been edited for length and clarity.

Question: Why do you usually start by measuring TSH levels?

Dr. Leung: We need to measure the thyroid status in a way that integrates more information about the long-term thyroid status and not small changes in thyroid hormone levels. TSH is made by the pituitary gland in the brain, which integrates information about the signals of high and low levels from each of the different thyroid hormones.

Now we can measure the actual thyroid hormones — primarily we’re talking about T3 and T4 — but if we do that, we are relying on a single snapshot in the bloodstream at that moment. The levels might change throughout the day in response to ongoing metabolism and outside stresses. So we usually start by measuring the TSH level, which is a good representation of the compilation of all those things over the past 30 days or so.

Question: How do you describe a low TSH result to patients?

Dr. Leung: Whenever we encounter a low TSH level, we want to repeat the test because it is a dynamic test, and it can change in response to several factors. If it is indeed low, we’re thinking that perhaps there’s a little bit of extra thyroid hormone in the body. It can be either temporary or more chronic, but that higher amount of thyroid hormone is telling the pituitary gland in the brain to start making less. So TSH levels go low when we need less thyroid hormone.

Question: What are some of the reasons for a low TSH level?

Dr. Leung: One of the most common situations for a temporarily low TSH level I see is what we call nonthyroidal illness, like a common cold or just being under the weather. Other things that can artifactually lower the TSH level could be the use of steroids, such as prednisone for asthma or some sort of a rheumatologic condition. Also, the TSH level could be low if a person has been recently exposed to very high amounts of iodine, such as iodinated contrast needed for a CT scan.

If the TSH level remains persistently low, usually in the presence of high thyroid hormone (T3 and/or T4) levels, the most common reason for hyperthyroidism is Graves disease, in which there are autoantibodies — measurable in the blood — that can stimulate the thyroid gland in the neck to make extra thyroid hormone.

Question: And what does an elevated TSH level mean?

Dr. Leung: Again, we want to confirm that it is elevated. We need at least two tests to confirm a high TSH level. A persistently elevated TSH level is a signal there might be low thyroid hormone levels in the body, which could be transient or more longer lasting.

Question: What are some of the most common causes of an elevated TSH level?

Dr. Leung: If the TSH level is confirmed high and the thyroid hormone levels are low, the most common cause of hypothyroidism here in the United States is Hashimoto thyroiditis.

Globally, iodine deficiency is the most common reason for hypothyroidism and may be a problem in parts of the globe where there are endemically low iodine levels in soil, crops, and the food supply like not having enough iodized salt. The thyroid is reliant on having enough iodine as a micronutrient to make thyroid hormone. If it doesn’t, the thyroid really can’t make thyroid hormone. It’s important to also remember, though, that having too much iodine can result in hypo- or hyperthyroidism.

Dr. Tsai: I take a glance at their medication list. Some of the patients are on methimazole or levothyroxine, and those medications should be adjusted first to normalize the TSH level. Other medications like lithium and amiodarone can also cause elevated TSH levels. We are also seeing a lot of patients on cancer therapies, such as tyrosine kinase inhibitors or immunotherapy, that can cause an elevated TSH level.

Question: If the repeat TSH test shows that TSH levels are still elevated, what comes next in your workup?

Dr. Tsai: If there’s not a real clear-cut diagnosis, I’ll order the thyroid peroxidase antibody and the thyroglobulin antibody, although thyroid peroxidase antibody, which is indicative of autoimmune thyroid disease, alone is usually sufficient to make that diagnosis.

Question: Should clinicians follow thyroid antibodies over time?

Dr. Tsai: I usually don’t repeat the antibody tests. In those circumstances where patients who were diagnosed 50-60 years ago and perhaps it is unknown if they had the thyroid antibodies measured at the time and now they’re saying, “Do I actually have Hashimoto’s?” or “Do I really need to continue this for the rest of my life?” I do repeat antibody tests to help gauge if the patient’s levothyroxine can be stopped.

Question: How important is it to follow T4 or T3 levels?

Dr. Tsai: T4 and T3 levels can help differentiate overt thyroid dysfunction — where T3 and/or T4 levels will be abnormal — from subclinical thyroid dysfunction — where T3 and T4 levels would be normal. In general, although we do not fully appreciate the best metric to monitor hypo- or hyperthyroidism, because some patients with a normal TSH level still may have symptoms of thyroid dysfunction, these peripheral thyroid hormone levels are usually the most helpful at the time of initial diagnosis.

Question: What are your criteria for initiating treatment for hypothyroidism?

Dr. Tsai: If the TSH level > 10 mIU/L, I recommend levothyroxine hormone replacement. A lot of published data support clinical benefit in this group.

There is a gray area in those patients who have a TSH level higher than the upper limit of the reference range but less than 10. If the patient doesn’t have overt hypothyroid symptoms, I discuss the findings with the patient but don’t really feel eager to treat. I recommend checking the levels again in 6 months to see where that TSH goes, and if it worsens or becomes greater than 10 mIU/L, I then recommend levothyroxine hormone replacement.

It is also important to note that a TSH level of 5-7 may be an acceptable range for older patients, and they do not require levothyroxine.

The other category is patients whose TSH level is greater than the upper limit of the normal reference range but less than 10 and with overt hypothyroid symptoms such as fatigue, unintentional weight gain, constipation, or cold intolerance. In these patients, it is worthwhile to try a low dose of levothyroxine (25-50 mcg/d) and repeat TSH and free T4 tests in 6-8 weeks and see if the TSH level normalizes.

Dr. Leung: When you look at subclinical hypothyroidism, the situation of an isolated high TSH level in the setting of normal T4 levels, if the TSH level is mildly elevated in the 5-7 mIU/L range, there’s a 60% chance that it will normalize within 6 months.

Going back to Karen’s point, a lot of people are started and maintained on low doses of thyroid hormone forever and ever. A recent study on levothyroxine use found half of the prescriptions were unnecessary.

Question: In an era where many patients obtain much of their health information from TikTok, what’s your approach with patients with a normal TSH level who feel that they should have more testing or start treatment?

Dr. Tsai: Fatigue is one of the common referrals we get into our endocrinology practice, and everyone is convinced that their thyroid is the culprit. It is important to note, however, that fatigue can be due to different diseases such as anemia, depression, sleep disorders, or a recent viral illness.

TSH tests are readily available and cheap. I don’t mind ordering the lab test again if it helps give the patient some reassurance. I also find that patients are relieved once they hear from their endocrinologist that their thyroid is unlikely to be the cause of their fatigue.

Some other endocrine causes we may consider additionally working up include adrenal insufficiency, vitamin D deficiency, and diabetes. A comprehensive metabolic panel and complete blood count is part of my workup to rule out any gross electrolyte abnormalities or any new diagnosis of anemia, liver disease, or chronic kidney disease.

Question: What are your criteria for recommending that someone see an endocrinologist?

Dr. Tsai: Our primary care colleagues can do a workup and interpretation of thyroid function tests in most cases. In the situations where the thyroid function test results are discordant (ie, elevated TSH and elevated free T4 levels or low TSH and low free T4 levels) or difficult to interpret, it would be appropriate to refer the patient to an endocrinologist.

One of the common referrals that we do get from the community is a patient’s thyroid function tests going from hyperthyroid to hypothyroid without a clear explanation or the patient is suboptimally controlled with levothyroxine or methimazole. In those circumstances, it would be worthwhile to send to an endocrinologist try to discern an underlying cause or for optimization of medication.

Dr. Leung and Dr. Tsai had no financial disclosures.
 

A version of this article appeared on Medscape.com.

If you’re like most primary care clinicians, your email inbox is flooded with messages from patients with questions about lab results. A common query: Should I be worried about an abnormal value on a test of thyroid-stimulating hormone (TSH)?

For guidance, this news organization spoke with Angela Leung, MD, associate professor of medicine in the Division of Endocrinology, Diabetes & Metabolism at the UCLA David Geffen School of Medicine and an endocrinologist at UCLA and the VA Greater Los Angeles Healthcare System, and Karen Tsai, MD, assistant clinical professor of endocrinology at City of Hope Comprehensive Cancer Center in Duarte, California. The following interview has been edited for length and clarity.

Question: Why do you usually start by measuring TSH levels?

Dr. Leung: We need to measure the thyroid status in a way that integrates more information about the long-term thyroid status and not small changes in thyroid hormone levels. TSH is made by the pituitary gland in the brain, which integrates information about the signals of high and low levels from each of the different thyroid hormones.

Now we can measure the actual thyroid hormones — primarily we’re talking about T3 and T4 — but if we do that, we are relying on a single snapshot in the bloodstream at that moment. The levels might change throughout the day in response to ongoing metabolism and outside stresses. So we usually start by measuring the TSH level, which is a good representation of the compilation of all those things over the past 30 days or so.

Question: How do you describe a low TSH result to patients?

Dr. Leung: Whenever we encounter a low TSH level, we want to repeat the test because it is a dynamic test, and it can change in response to several factors. If it is indeed low, we’re thinking that perhaps there’s a little bit of extra thyroid hormone in the body. It can be either temporary or more chronic, but that higher amount of thyroid hormone is telling the pituitary gland in the brain to start making less. So TSH levels go low when we need less thyroid hormone.

Question: What are some of the reasons for a low TSH level?

Dr. Leung: One of the most common situations for a temporarily low TSH level I see is what we call nonthyroidal illness, like a common cold or just being under the weather. Other things that can artifactually lower the TSH level could be the use of steroids, such as prednisone for asthma or some sort of a rheumatologic condition. Also, the TSH level could be low if a person has been recently exposed to very high amounts of iodine, such as iodinated contrast needed for a CT scan.

If the TSH level remains persistently low, usually in the presence of high thyroid hormone (T3 and/or T4) levels, the most common reason for hyperthyroidism is Graves disease, in which there are autoantibodies — measurable in the blood — that can stimulate the thyroid gland in the neck to make extra thyroid hormone.

Question: And what does an elevated TSH level mean?

Dr. Leung: Again, we want to confirm that it is elevated. We need at least two tests to confirm a high TSH level. A persistently elevated TSH level is a signal there might be low thyroid hormone levels in the body, which could be transient or more longer lasting.

Question: What are some of the most common causes of an elevated TSH level?

Dr. Leung: If the TSH level is confirmed high and the thyroid hormone levels are low, the most common cause of hypothyroidism here in the United States is Hashimoto thyroiditis.

Globally, iodine deficiency is the most common reason for hypothyroidism and may be a problem in parts of the globe where there are endemically low iodine levels in soil, crops, and the food supply like not having enough iodized salt. The thyroid is reliant on having enough iodine as a micronutrient to make thyroid hormone. If it doesn’t, the thyroid really can’t make thyroid hormone. It’s important to also remember, though, that having too much iodine can result in hypo- or hyperthyroidism.

Dr. Tsai: I take a glance at their medication list. Some of the patients are on methimazole or levothyroxine, and those medications should be adjusted first to normalize the TSH level. Other medications like lithium and amiodarone can also cause elevated TSH levels. We are also seeing a lot of patients on cancer therapies, such as tyrosine kinase inhibitors or immunotherapy, that can cause an elevated TSH level.

Question: If the repeat TSH test shows that TSH levels are still elevated, what comes next in your workup?

Dr. Tsai: If there’s not a real clear-cut diagnosis, I’ll order the thyroid peroxidase antibody and the thyroglobulin antibody, although thyroid peroxidase antibody, which is indicative of autoimmune thyroid disease, alone is usually sufficient to make that diagnosis.

Question: Should clinicians follow thyroid antibodies over time?

Dr. Tsai: I usually don’t repeat the antibody tests. In those circumstances where patients who were diagnosed 50-60 years ago and perhaps it is unknown if they had the thyroid antibodies measured at the time and now they’re saying, “Do I actually have Hashimoto’s?” or “Do I really need to continue this for the rest of my life?” I do repeat antibody tests to help gauge if the patient’s levothyroxine can be stopped.

Question: How important is it to follow T4 or T3 levels?

Dr. Tsai: T4 and T3 levels can help differentiate overt thyroid dysfunction — where T3 and/or T4 levels will be abnormal — from subclinical thyroid dysfunction — where T3 and T4 levels would be normal. In general, although we do not fully appreciate the best metric to monitor hypo- or hyperthyroidism, because some patients with a normal TSH level still may have symptoms of thyroid dysfunction, these peripheral thyroid hormone levels are usually the most helpful at the time of initial diagnosis.

Question: What are your criteria for initiating treatment for hypothyroidism?

Dr. Tsai: If the TSH level > 10 mIU/L, I recommend levothyroxine hormone replacement. A lot of published data support clinical benefit in this group.

There is a gray area in those patients who have a TSH level higher than the upper limit of the reference range but less than 10. If the patient doesn’t have overt hypothyroid symptoms, I discuss the findings with the patient but don’t really feel eager to treat. I recommend checking the levels again in 6 months to see where that TSH goes, and if it worsens or becomes greater than 10 mIU/L, I then recommend levothyroxine hormone replacement.

It is also important to note that a TSH level of 5-7 may be an acceptable range for older patients, and they do not require levothyroxine.

The other category is patients whose TSH level is greater than the upper limit of the normal reference range but less than 10 and with overt hypothyroid symptoms such as fatigue, unintentional weight gain, constipation, or cold intolerance. In these patients, it is worthwhile to try a low dose of levothyroxine (25-50 mcg/d) and repeat TSH and free T4 tests in 6-8 weeks and see if the TSH level normalizes.

Dr. Leung: When you look at subclinical hypothyroidism, the situation of an isolated high TSH level in the setting of normal T4 levels, if the TSH level is mildly elevated in the 5-7 mIU/L range, there’s a 60% chance that it will normalize within 6 months.

Going back to Karen’s point, a lot of people are started and maintained on low doses of thyroid hormone forever and ever. A recent study on levothyroxine use found half of the prescriptions were unnecessary.

Question: In an era where many patients obtain much of their health information from TikTok, what’s your approach with patients with a normal TSH level who feel that they should have more testing or start treatment?

Dr. Tsai: Fatigue is one of the common referrals we get into our endocrinology practice, and everyone is convinced that their thyroid is the culprit. It is important to note, however, that fatigue can be due to different diseases such as anemia, depression, sleep disorders, or a recent viral illness.

TSH tests are readily available and cheap. I don’t mind ordering the lab test again if it helps give the patient some reassurance. I also find that patients are relieved once they hear from their endocrinologist that their thyroid is unlikely to be the cause of their fatigue.

Some other endocrine causes we may consider additionally working up include adrenal insufficiency, vitamin D deficiency, and diabetes. A comprehensive metabolic panel and complete blood count is part of my workup to rule out any gross electrolyte abnormalities or any new diagnosis of anemia, liver disease, or chronic kidney disease.

Question: What are your criteria for recommending that someone see an endocrinologist?

Dr. Tsai: Our primary care colleagues can do a workup and interpretation of thyroid function tests in most cases. In the situations where the thyroid function test results are discordant (ie, elevated TSH and elevated free T4 levels or low TSH and low free T4 levels) or difficult to interpret, it would be appropriate to refer the patient to an endocrinologist.

One of the common referrals that we do get from the community is a patient’s thyroid function tests going from hyperthyroid to hypothyroid without a clear explanation or the patient is suboptimally controlled with levothyroxine or methimazole. In those circumstances, it would be worthwhile to send to an endocrinologist try to discern an underlying cause or for optimization of medication.

Dr. Leung and Dr. Tsai had no financial disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic/bariatric surgery (MBS) reduces thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid hormone resistance indices in patients with obesity, changes strongly correlated with improvement in body composition.

METHODOLOGY:

• Recent studies have linked obesity with increased levels of TSH and thyroid hormones; however, the role that body fat distribution plays in this association remains unclear.
• This retrospective observational study evaluated the effects of MBS on thyroid hormone levels and thyroid hormone resistance in euthyroid individuals with obesity, focusing on the correlation with changes in body composition.
• Researchers included 470 patients with obesity (mean age, 33.4 years; mean body mass index [BMI], 37.9; 63.2% women) and 118 control individuals without obesity (mean BMI, 21.8), who had had normal levels of TSH, fT3, and free thyroxine.
• Among the patients with obesity, 125 underwent MBS and had thyroid tests both before and ≥ 3 months after surgery.
• Data on body composition and thyroid function were collected, and correlations between baseline and changes in thyroid function and body composition were assessed.

TAKEAWAY:

• Individuals with obesity had higher baseline TSH and fT3 levels (P < .001) and thyroid feedback quantile-based index (TFQI; P = .047) than those without obesity, with the values decreasing after MBS (all P < .001).
• Among individuals with obesity, preoperative TSH was positively correlated with the visceral fat area (VFA; P = .019) and body fat percentage (P = .013) and negatively correlated with skeletal muscle mass percentage (P = .024)
• The decrease in TSH post-surgery positively correlated with decreased VFA (P = .021) and decreased body fat percentage (P = .031).
• Decrease in VFA and body fat percentage after MBS was also associated with improved central thyroid hormone resistance indicated by TFQI.

IN PRACTICE:

“The relationship between obesity and [thyroid hormone] is bidirectional, indicating that addressing underlying thyroid disturbance could potentially benefit weight loss and metabolism,” the authors wrote.

SOURCE:

This study was led by Yu Yan, MD, Department of Pancreatic and Metabolic Surgery, Medical School of Southeast University, Nanjing Drum Tower Hospital, Nanjing, China, and published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The retrospective nature of this study limited the ability to definitively attribute changes in thyroid function and thyroid hormone resistance to changes in body composition. The relatively short duration of the study and the exclusion of individuals taking medications affecting thyroid function may also limit the generalizability of the findings.

DISCLOSURES:

This study was supported by the Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. The authors declared no potential conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Metabolic/bariatric surgery (MBS) reduces thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid hormone resistance indices in patients with obesity, changes strongly correlated with improvement in body composition.

METHODOLOGY:

• Recent studies have linked obesity with increased levels of TSH and thyroid hormones; however, the role that body fat distribution plays in this association remains unclear.
• This retrospective observational study evaluated the effects of MBS on thyroid hormone levels and thyroid hormone resistance in euthyroid individuals with obesity, focusing on the correlation with changes in body composition.
• Researchers included 470 patients with obesity (mean age, 33.4 years; mean body mass index [BMI], 37.9; 63.2% women) and 118 control individuals without obesity (mean BMI, 21.8), who had had normal levels of TSH, fT3, and free thyroxine.
• Among the patients with obesity, 125 underwent MBS and had thyroid tests both before and ≥ 3 months after surgery.
• Data on body composition and thyroid function were collected, and correlations between baseline and changes in thyroid function and body composition were assessed.

TAKEAWAY:

• Individuals with obesity had higher baseline TSH and fT3 levels (P < .001) and thyroid feedback quantile-based index (TFQI; P = .047) than those without obesity, with the values decreasing after MBS (all P < .001).
• Among individuals with obesity, preoperative TSH was positively correlated with the visceral fat area (VFA; P = .019) and body fat percentage (P = .013) and negatively correlated with skeletal muscle mass percentage (P = .024)
• The decrease in TSH post-surgery positively correlated with decreased VFA (P = .021) and decreased body fat percentage (P = .031).
• Decrease in VFA and body fat percentage after MBS was also associated with improved central thyroid hormone resistance indicated by TFQI.

IN PRACTICE:

“The relationship between obesity and [thyroid hormone] is bidirectional, indicating that addressing underlying thyroid disturbance could potentially benefit weight loss and metabolism,” the authors wrote.

SOURCE:

This study was led by Yu Yan, MD, Department of Pancreatic and Metabolic Surgery, Medical School of Southeast University, Nanjing Drum Tower Hospital, Nanjing, China, and published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The retrospective nature of this study limited the ability to definitively attribute changes in thyroid function and thyroid hormone resistance to changes in body composition. The relatively short duration of the study and the exclusion of individuals taking medications affecting thyroid function may also limit the generalizability of the findings.

DISCLOSURES:

This study was supported by the Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. The authors declared no potential conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Metabolic/bariatric surgery (MBS) reduces thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid hormone resistance indices in patients with obesity, changes strongly correlated with improvement in body composition.

METHODOLOGY:

• Recent studies have linked obesity with increased levels of TSH and thyroid hormones; however, the role that body fat distribution plays in this association remains unclear.
• This retrospective observational study evaluated the effects of MBS on thyroid hormone levels and thyroid hormone resistance in euthyroid individuals with obesity, focusing on the correlation with changes in body composition.
• Researchers included 470 patients with obesity (mean age, 33.4 years; mean body mass index [BMI], 37.9; 63.2% women) and 118 control individuals without obesity (mean BMI, 21.8), who had had normal levels of TSH, fT3, and free thyroxine.
• Among the patients with obesity, 125 underwent MBS and had thyroid tests both before and ≥ 3 months after surgery.
• Data on body composition and thyroid function were collected, and correlations between baseline and changes in thyroid function and body composition were assessed.

TAKEAWAY:

• Individuals with obesity had higher baseline TSH and fT3 levels (P < .001) and thyroid feedback quantile-based index (TFQI; P = .047) than those without obesity, with the values decreasing after MBS (all P < .001).
• Among individuals with obesity, preoperative TSH was positively correlated with the visceral fat area (VFA; P = .019) and body fat percentage (P = .013) and negatively correlated with skeletal muscle mass percentage (P = .024)
• The decrease in TSH post-surgery positively correlated with decreased VFA (P = .021) and decreased body fat percentage (P = .031).
• Decrease in VFA and body fat percentage after MBS was also associated with improved central thyroid hormone resistance indicated by TFQI.

IN PRACTICE:

“The relationship between obesity and [thyroid hormone] is bidirectional, indicating that addressing underlying thyroid disturbance could potentially benefit weight loss and metabolism,” the authors wrote.

SOURCE:

This study was led by Yu Yan, MD, Department of Pancreatic and Metabolic Surgery, Medical School of Southeast University, Nanjing Drum Tower Hospital, Nanjing, China, and published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The retrospective nature of this study limited the ability to definitively attribute changes in thyroid function and thyroid hormone resistance to changes in body composition. The relatively short duration of the study and the exclusion of individuals taking medications affecting thyroid function may also limit the generalizability of the findings.

DISCLOSURES:

This study was supported by the Fundings for Clinical Trials from the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. The authors declared no potential conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. 

Paul, we’re going to talk about our primary hyperparathyroidism podcast with Dr. Lindsay Kuo. It’s a topic that I feel much more clear on now.

Now, Paul, in primary care, you see a lot of calcium that is just slightly high. Can we just blame that on thiazide diuretics?

Paul N. Williams, MD: It’s a place to start. As you’re starting to think about the possible etiologies, primary hyperparathyroidism and malignancy are the two that roll right off the tongue, but it is worth going back to the patient’s medication list and making sure you’re not missing something.

Thiazides famously cause hypercalcemia, but in some of the reading I did for this episode, they may just uncover it a little bit early. Patients who are on thiazides who become hypercalcemic seem to go on to develop primary hyperthyroidism anyway. So I don’t think you can solely blame the thiazide.

Another medication that can be causative is lithium. So a good place to look first after you’ve repeated the labs and confirmed hypercalcemia is the patient’s medication list. 

Dr. Watto: We’ve talked before about the basic workup for hypercalcemia, and determining whether it’s PTH dependent or PTH independent. On the podcast, we talk more about the full workup, but I wanted to talk about the classic symptoms. Our expert made the point that we don’t see them as much anymore, although we do see kidney stones. People used to present very late in the disease because they weren’t having labs done routinely.

The classic symptoms include osteoporosis and bone tumors. People can get nephrocalcinosis and kidney stones. I hadn’t really thought of it this way because we’re used to diagnosing it early now. Do you feel the same? 

Dr. Williams: As labs have started routinely reporting calcium levels, this is more and more often how it’s picked up. The other aspect is that as we are screening for and finding osteoporosis, part of the workup almost always involves getting a parathyroid hormone and a calcium level. We’re seeing these lab abnormalities before we’re seeing symptoms, which is good.

But it also makes things more diagnostically thorny.

Dr. Watto: Dr. Lindsay Kuo made the point that when she sees patients before and after surgery, she’s aware of these nonclassic symptoms — the stones, bones, groans, and the psychiatric overtones that can be anything from fatigue or irritability to dysphoria.

Some people have a generalized weakness that’s very nonspecific. Dr. Kuo said that sometimes these symptoms will disappear after surgery. The patients may just have gotten used to them, or they thought these symptoms were caused by something else, but after surgery they went away.

There are these nonclassic symptoms that are harder to pin down. I was surprised by that.

Dr. Williams: She mentioned polydipsia and polyuria, which have been reported in other studies. It seems like it can be anything. You have to take a good history, but none of those things in and of themselves is an indication for operating unless the patient has the classic renal or bone manifestations. 

Dr. Watto: The other thing we talked about is a normal calcium level in a patient with primary hyperparathyroidism, or the finding of a PTH level in the normal range but with a high calcium level that is inappropriate. Can you talk a little bit about those two situations? 

Dr. Williams: They’re hard to say but kind of easy to manage because you treat them the same way as someone who has elevated calcium and PTH levels. 

The normocalcemic patient is something we might stumble across with osteoporosis screening. Initially the calcium level is elevated, so you repeat it and it’s normal but with an elevated PTH level. You’re like, shoot. Now what?

It turns out that most endocrine surgeons say that the indications for surgery for the classic form of primary hyperparathyroidism apply to these patients as well, and it probably helps with the bone outcomes, which is one of the things they follow most closely. If you have hypercalcemia, you should have a suppressed PTH level, the so-called normohormonal hyperparathyroidism, which is not normal at all. So even if the PTH is in the normal range, it’s still relatively elevated compared with what it should be. That situation is treated in the same way as the classic elevated PTH and elevated calcium levels.

Dr. Watto: If the calcium is abnormal and the PTH is not quite what you’d expect it to be, you can always ask your friendly neighborhood endocrinologist to help you figure out whether the patient really has one of these conditions. You have to make sure that they don’t have a simple secondary cause like a low vitamin D level. In that case, you fix the vitamin D and then recheck the numbers to see if they’ve normalized. But I have found a bunch of these edge cases in which it has been helpful to confer with an endocrinologist, especially before you send someone to a surgeon to take out their parathyroid gland. 

This was a really fantastic conversation. If you want to hear the full podcast episode, click here.
 

Dr. Watto, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, has disclosed no relevant financial relationships. Dr. Williams, Associate Professor of Clinical Medicine, Department of General Internal Medicine, Lewis Katz School of Medicine; Staff Physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania, served as a director, officer, partner, employee, adviser, consultant, or trustee for The Curbsiders, and has received income in an amount equal to or greater than $250 from The Curbsiders.

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

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. 

Paul, we’re going to talk about our primary hyperparathyroidism podcast with Dr. Lindsay Kuo. It’s a topic that I feel much more clear on now.

Now, Paul, in primary care, you see a lot of calcium that is just slightly high. Can we just blame that on thiazide diuretics?

Paul N. Williams, MD: It’s a place to start. As you’re starting to think about the possible etiologies, primary hyperparathyroidism and malignancy are the two that roll right off the tongue, but it is worth going back to the patient’s medication list and making sure you’re not missing something.

Thiazides famously cause hypercalcemia, but in some of the reading I did for this episode, they may just uncover it a little bit early. Patients who are on thiazides who become hypercalcemic seem to go on to develop primary hyperthyroidism anyway. So I don’t think you can solely blame the thiazide.

Another medication that can be causative is lithium. So a good place to look first after you’ve repeated the labs and confirmed hypercalcemia is the patient’s medication list. 

Dr. Watto: We’ve talked before about the basic workup for hypercalcemia, and determining whether it’s PTH dependent or PTH independent. On the podcast, we talk more about the full workup, but I wanted to talk about the classic symptoms. Our expert made the point that we don’t see them as much anymore, although we do see kidney stones. People used to present very late in the disease because they weren’t having labs done routinely.

The classic symptoms include osteoporosis and bone tumors. People can get nephrocalcinosis and kidney stones. I hadn’t really thought of it this way because we’re used to diagnosing it early now. Do you feel the same? 

Dr. Williams: As labs have started routinely reporting calcium levels, this is more and more often how it’s picked up. The other aspect is that as we are screening for and finding osteoporosis, part of the workup almost always involves getting a parathyroid hormone and a calcium level. We’re seeing these lab abnormalities before we’re seeing symptoms, which is good.

But it also makes things more diagnostically thorny.

Dr. Watto: Dr. Lindsay Kuo made the point that when she sees patients before and after surgery, she’s aware of these nonclassic symptoms — the stones, bones, groans, and the psychiatric overtones that can be anything from fatigue or irritability to dysphoria.

Some people have a generalized weakness that’s very nonspecific. Dr. Kuo said that sometimes these symptoms will disappear after surgery. The patients may just have gotten used to them, or they thought these symptoms were caused by something else, but after surgery they went away.

There are these nonclassic symptoms that are harder to pin down. I was surprised by that.

Dr. Williams: She mentioned polydipsia and polyuria, which have been reported in other studies. It seems like it can be anything. You have to take a good history, but none of those things in and of themselves is an indication for operating unless the patient has the classic renal or bone manifestations. 

Dr. Watto: The other thing we talked about is a normal calcium level in a patient with primary hyperparathyroidism, or the finding of a PTH level in the normal range but with a high calcium level that is inappropriate. Can you talk a little bit about those two situations? 

Dr. Williams: They’re hard to say but kind of easy to manage because you treat them the same way as someone who has elevated calcium and PTH levels. 

The normocalcemic patient is something we might stumble across with osteoporosis screening. Initially the calcium level is elevated, so you repeat it and it’s normal but with an elevated PTH level. You’re like, shoot. Now what?

It turns out that most endocrine surgeons say that the indications for surgery for the classic form of primary hyperparathyroidism apply to these patients as well, and it probably helps with the bone outcomes, which is one of the things they follow most closely. If you have hypercalcemia, you should have a suppressed PTH level, the so-called normohormonal hyperparathyroidism, which is not normal at all. So even if the PTH is in the normal range, it’s still relatively elevated compared with what it should be. That situation is treated in the same way as the classic elevated PTH and elevated calcium levels.

Dr. Watto: If the calcium is abnormal and the PTH is not quite what you’d expect it to be, you can always ask your friendly neighborhood endocrinologist to help you figure out whether the patient really has one of these conditions. You have to make sure that they don’t have a simple secondary cause like a low vitamin D level. In that case, you fix the vitamin D and then recheck the numbers to see if they’ve normalized. But I have found a bunch of these edge cases in which it has been helpful to confer with an endocrinologist, especially before you send someone to a surgeon to take out their parathyroid gland. 

This was a really fantastic conversation. If you want to hear the full podcast episode, click here.
 

Dr. Watto, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, has disclosed no relevant financial relationships. Dr. Williams, Associate Professor of Clinical Medicine, Department of General Internal Medicine, Lewis Katz School of Medicine; Staff Physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania, served as a director, officer, partner, employee, adviser, consultant, or trustee for The Curbsiders, and has received income in an amount equal to or greater than $250 from The Curbsiders.

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

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. 

Paul, we’re going to talk about our primary hyperparathyroidism podcast with Dr. Lindsay Kuo. It’s a topic that I feel much more clear on now.

Now, Paul, in primary care, you see a lot of calcium that is just slightly high. Can we just blame that on thiazide diuretics?

Paul N. Williams, MD: It’s a place to start. As you’re starting to think about the possible etiologies, primary hyperparathyroidism and malignancy are the two that roll right off the tongue, but it is worth going back to the patient’s medication list and making sure you’re not missing something.

Thiazides famously cause hypercalcemia, but in some of the reading I did for this episode, they may just uncover it a little bit early. Patients who are on thiazides who become hypercalcemic seem to go on to develop primary hyperthyroidism anyway. So I don’t think you can solely blame the thiazide.

Another medication that can be causative is lithium. So a good place to look first after you’ve repeated the labs and confirmed hypercalcemia is the patient’s medication list. 

Dr. Watto: We’ve talked before about the basic workup for hypercalcemia, and determining whether it’s PTH dependent or PTH independent. On the podcast, we talk more about the full workup, but I wanted to talk about the classic symptoms. Our expert made the point that we don’t see them as much anymore, although we do see kidney stones. People used to present very late in the disease because they weren’t having labs done routinely.

The classic symptoms include osteoporosis and bone tumors. People can get nephrocalcinosis and kidney stones. I hadn’t really thought of it this way because we’re used to diagnosing it early now. Do you feel the same? 

Dr. Williams: As labs have started routinely reporting calcium levels, this is more and more often how it’s picked up. The other aspect is that as we are screening for and finding osteoporosis, part of the workup almost always involves getting a parathyroid hormone and a calcium level. We’re seeing these lab abnormalities before we’re seeing symptoms, which is good.

But it also makes things more diagnostically thorny.

Dr. Watto: Dr. Lindsay Kuo made the point that when she sees patients before and after surgery, she’s aware of these nonclassic symptoms — the stones, bones, groans, and the psychiatric overtones that can be anything from fatigue or irritability to dysphoria.

Some people have a generalized weakness that’s very nonspecific. Dr. Kuo said that sometimes these symptoms will disappear after surgery. The patients may just have gotten used to them, or they thought these symptoms were caused by something else, but after surgery they went away.

There are these nonclassic symptoms that are harder to pin down. I was surprised by that.

Dr. Williams: She mentioned polydipsia and polyuria, which have been reported in other studies. It seems like it can be anything. You have to take a good history, but none of those things in and of themselves is an indication for operating unless the patient has the classic renal or bone manifestations. 

Dr. Watto: The other thing we talked about is a normal calcium level in a patient with primary hyperparathyroidism, or the finding of a PTH level in the normal range but with a high calcium level that is inappropriate. Can you talk a little bit about those two situations? 

Dr. Williams: They’re hard to say but kind of easy to manage because you treat them the same way as someone who has elevated calcium and PTH levels. 

The normocalcemic patient is something we might stumble across with osteoporosis screening. Initially the calcium level is elevated, so you repeat it and it’s normal but with an elevated PTH level. You’re like, shoot. Now what?

It turns out that most endocrine surgeons say that the indications for surgery for the classic form of primary hyperparathyroidism apply to these patients as well, and it probably helps with the bone outcomes, which is one of the things they follow most closely. If you have hypercalcemia, you should have a suppressed PTH level, the so-called normohormonal hyperparathyroidism, which is not normal at all. So even if the PTH is in the normal range, it’s still relatively elevated compared with what it should be. That situation is treated in the same way as the classic elevated PTH and elevated calcium levels.

Dr. Watto: If the calcium is abnormal and the PTH is not quite what you’d expect it to be, you can always ask your friendly neighborhood endocrinologist to help you figure out whether the patient really has one of these conditions. You have to make sure that they don’t have a simple secondary cause like a low vitamin D level. In that case, you fix the vitamin D and then recheck the numbers to see if they’ve normalized. But I have found a bunch of these edge cases in which it has been helpful to confer with an endocrinologist, especially before you send someone to a surgeon to take out their parathyroid gland. 

This was a really fantastic conversation. If you want to hear the full podcast episode, click here.
 

Dr. Watto, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, has disclosed no relevant financial relationships. Dr. Williams, Associate Professor of Clinical Medicine, Department of General Internal Medicine, Lewis Katz School of Medicine; Staff Physician, Department of General Internal Medicine, Temple Internal Medicine Associates, Philadelphia, Pennsylvania, served as a director, officer, partner, employee, adviser, consultant, or trustee for The Curbsiders, and has received income in an amount equal to or greater than $250 from The Curbsiders.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

TOPLINE:

Long-term exposure to particulate matter < 2.5 μm in diameter (PM_2.5) is linked to a higher risk for infertility in men. Exposure to road traffic noise is associated with a higher risk for infertility in women aged > 35 years and possibly in men aged > 37 years.

METHODOLOGY:

• This nationwide prospective cohort study evaluated the association between long-term exposure to road traffic noise and PM_2.5 and infertility in 526,056 men (mean age, 33.6 years) and 377,850 women (mean age, 32.7 years) who were cohabiting or married, had fewer than two children, and lived in Denmark between 2000 and 2017.
• Residential exposure to road traffic noise (most exposed facade of the home) and PM_2.5 was estimated using validated models and linked to data from national registers.
• Diagnoses of infertility were identified in men and women from the Danish National Patient Register over a mean follow-up of 4.3 years and 4.2 years, respectively.

TAKEAWAY:

• Each 2.9 µg/m³ increase in the 5-year average exposure to PM_2.5 was associated with a 24% increase in the risk for infertility in men aged 30-45 years (adjusted hazard ratio [aHR], 1.24).
• No significant association was found between exposure to PM_2.5 and infertility in women.
• Each 10.2 dB increase in the 5-year average exposure to road traffic noise was associated with a 14% increase in infertility (aHR, 1.14; 95% CI, 1.10-1.18) in women aged 35-45 years.
• Exposure to noise was associated with a reduced risk for infertility in men aged 30.0-36.9 years (aHR, 0.93; 95% CI, 0.91-0.96) and an increased risk in those aged 37-45 years (aHR, 1.06; 95% CI, 1.02-1.11).

IN PRACTICE:

“As many Western countries are facing declining birth rates and increasing maternal age at the birth of a first child, knowledge on environmental pollutants affecting fertility is crucial,” the authors of the study wrote. “It suggests that political implementation of air pollution and noise mitigations may be important tools for improving birth rates in the Western world,” they added.

SOURCE:

The study, led by Mette Sorensen, of the Danish Cancer Institute in Copenhagen, Denmark, was published online in The BMJ.

LIMITATIONS:

The study’s reliance on register data meant information on lifestyle factors such as alcohol use, body mass index, and smoking was unavailable. The lack of data on exposure to noise and PM_2.5 at work and during leisure activities may affect the size and statistical precision of risk estimates.

DISCLOSURES:

The study did not receive any external funding. The authors declared no relevant conflicts of interest.

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

TOPLINE:

Long-term exposure to particulate matter < 2.5 μm in diameter (PM_2.5) is linked to a higher risk for infertility in men. Exposure to road traffic noise is associated with a higher risk for infertility in women aged > 35 years and possibly in men aged > 37 years.

METHODOLOGY:

• This nationwide prospective cohort study evaluated the association between long-term exposure to road traffic noise and PM_2.5 and infertility in 526,056 men (mean age, 33.6 years) and 377,850 women (mean age, 32.7 years) who were cohabiting or married, had fewer than two children, and lived in Denmark between 2000 and 2017.
• Residential exposure to road traffic noise (most exposed facade of the home) and PM_2.5 was estimated using validated models and linked to data from national registers.
• Diagnoses of infertility were identified in men and women from the Danish National Patient Register over a mean follow-up of 4.3 years and 4.2 years, respectively.

TAKEAWAY:

• Each 2.9 µg/m³ increase in the 5-year average exposure to PM_2.5 was associated with a 24% increase in the risk for infertility in men aged 30-45 years (adjusted hazard ratio [aHR], 1.24).
• No significant association was found between exposure to PM_2.5 and infertility in women.
• Each 10.2 dB increase in the 5-year average exposure to road traffic noise was associated with a 14% increase in infertility (aHR, 1.14; 95% CI, 1.10-1.18) in women aged 35-45 years.
• Exposure to noise was associated with a reduced risk for infertility in men aged 30.0-36.9 years (aHR, 0.93; 95% CI, 0.91-0.96) and an increased risk in those aged 37-45 years (aHR, 1.06; 95% CI, 1.02-1.11).

IN PRACTICE:

“As many Western countries are facing declining birth rates and increasing maternal age at the birth of a first child, knowledge on environmental pollutants affecting fertility is crucial,” the authors of the study wrote. “It suggests that political implementation of air pollution and noise mitigations may be important tools for improving birth rates in the Western world,” they added.

SOURCE:

The study, led by Mette Sorensen, of the Danish Cancer Institute in Copenhagen, Denmark, was published online in The BMJ.

LIMITATIONS:

The study’s reliance on register data meant information on lifestyle factors such as alcohol use, body mass index, and smoking was unavailable. The lack of data on exposure to noise and PM_2.5 at work and during leisure activities may affect the size and statistical precision of risk estimates.

DISCLOSURES:

The study did not receive any external funding. The authors declared no relevant conflicts of interest.

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

TOPLINE:

Long-term exposure to particulate matter < 2.5 μm in diameter (PM_2.5) is linked to a higher risk for infertility in men. Exposure to road traffic noise is associated with a higher risk for infertility in women aged > 35 years and possibly in men aged > 37 years.

METHODOLOGY:

• This nationwide prospective cohort study evaluated the association between long-term exposure to road traffic noise and PM_2.5 and infertility in 526,056 men (mean age, 33.6 years) and 377,850 women (mean age, 32.7 years) who were cohabiting or married, had fewer than two children, and lived in Denmark between 2000 and 2017.
• Residential exposure to road traffic noise (most exposed facade of the home) and PM_2.5 was estimated using validated models and linked to data from national registers.
• Diagnoses of infertility were identified in men and women from the Danish National Patient Register over a mean follow-up of 4.3 years and 4.2 years, respectively.

TAKEAWAY:

• Each 2.9 µg/m³ increase in the 5-year average exposure to PM_2.5 was associated with a 24% increase in the risk for infertility in men aged 30-45 years (adjusted hazard ratio [aHR], 1.24).
• No significant association was found between exposure to PM_2.5 and infertility in women.
• Each 10.2 dB increase in the 5-year average exposure to road traffic noise was associated with a 14% increase in infertility (aHR, 1.14; 95% CI, 1.10-1.18) in women aged 35-45 years.
• Exposure to noise was associated with a reduced risk for infertility in men aged 30.0-36.9 years (aHR, 0.93; 95% CI, 0.91-0.96) and an increased risk in those aged 37-45 years (aHR, 1.06; 95% CI, 1.02-1.11).

IN PRACTICE:

“As many Western countries are facing declining birth rates and increasing maternal age at the birth of a first child, knowledge on environmental pollutants affecting fertility is crucial,” the authors of the study wrote. “It suggests that political implementation of air pollution and noise mitigations may be important tools for improving birth rates in the Western world,” they added.

SOURCE:

The study, led by Mette Sorensen, of the Danish Cancer Institute in Copenhagen, Denmark, was published online in The BMJ.

LIMITATIONS:

The study’s reliance on register data meant information on lifestyle factors such as alcohol use, body mass index, and smoking was unavailable. The lack of data on exposure to noise and PM_2.5 at work and during leisure activities may affect the size and statistical precision of risk estimates.

DISCLOSURES:

The study did not receive any external funding. The authors declared no relevant conflicts of interest.

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

TOPLINE:

For older adults with obesity, bariatric surgery does not appear to significantly reduce the risk for obesity-related cancer and cardiovascular disease (CVD), as it does in younger adults.

METHODOLOGY:

• Bariatric surgery has been shown to decrease the risk for obesity-related cancer and CVD but is typically reserved for patients aged < 60 years. Whether the same holds for patients who undergo surgery at older ages is unclear.
• Researchers analyzed nationwide data from three countries (Denmark, Finland, and Sweden) to compare patients with no history of cancer or CVD and age ≥ 60 years who underwent bariatric surgery against matched controls who received nonoperative treatment for obesity.
• The main outcome was obesity-related cancer, defined as a composite outcome of breast, endometrial, esophageal, colorectal, and kidney cancer. The secondary outcome was CVD, defined as a composite of myocardial infarction, ischemic stroke, and cerebral hemorrhage.
• Analyses were adjusted for diabetes, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, kidney disease, and frailty.

TAKEAWAY:

• Of the 15,300 patients (66.4% women) included, 2550 underwent bariatric surgery (including gastric bypass in 1930) and 12,750 matched controls received nonoperative treatment for obesity.
• During a median 5.8 years of follow-up, 658 (4.3%) people developed obesity-related cancer and 1436 (9.4%) developed CVD.
• Bariatric surgery in adults aged ≥ 60 years was not associated with a reduced risk for obesity-related cancer (hazard ratio [HR], 0.81) or CVD (HR, 0.86) compared with matched nonoperative controls.
• Bariatric surgery appeared to be associated with a decreased risk for obesity-related cancer in women (HR, 0.76).
• There was a decreased risk for both obesity-related cancer (HR, 0.74) and CVD (HR, 0.82) in patients who underwent gastric bypass.

IN PRACTICE:

“The findings from this study suggest a limited role of bariatric surgery in older patients for the prevention of obesity-related cancer or cardiovascular disease,” the authors wrote, noting that this “may be explained by the poorer weight loss and resolution of comorbidities observed in patients who underwent surgery at an older age.”

SOURCE:

The study, with first author Peter Gerber, MD, PhD, Department of Surgery, Capio St Göran’s Hospital, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Data on smoking status and body mass index were not available. The observational design limited the ability to draw causal inferences. The null association between bariatric surgery and outcomes may be due to limited power.

DISCLOSURES:

The study was funded by the Swedish Society of Medicine. The authors reported no conflicts of interest.

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

TOPLINE:

For older adults with obesity, bariatric surgery does not appear to significantly reduce the risk for obesity-related cancer and cardiovascular disease (CVD), as it does in younger adults.

METHODOLOGY:

• Bariatric surgery has been shown to decrease the risk for obesity-related cancer and CVD but is typically reserved for patients aged < 60 years. Whether the same holds for patients who undergo surgery at older ages is unclear.
• Researchers analyzed nationwide data from three countries (Denmark, Finland, and Sweden) to compare patients with no history of cancer or CVD and age ≥ 60 years who underwent bariatric surgery against matched controls who received nonoperative treatment for obesity.
• The main outcome was obesity-related cancer, defined as a composite outcome of breast, endometrial, esophageal, colorectal, and kidney cancer. The secondary outcome was CVD, defined as a composite of myocardial infarction, ischemic stroke, and cerebral hemorrhage.
• Analyses were adjusted for diabetes, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, kidney disease, and frailty.

TAKEAWAY:

• Of the 15,300 patients (66.4% women) included, 2550 underwent bariatric surgery (including gastric bypass in 1930) and 12,750 matched controls received nonoperative treatment for obesity.
• During a median 5.8 years of follow-up, 658 (4.3%) people developed obesity-related cancer and 1436 (9.4%) developed CVD.
• Bariatric surgery in adults aged ≥ 60 years was not associated with a reduced risk for obesity-related cancer (hazard ratio [HR], 0.81) or CVD (HR, 0.86) compared with matched nonoperative controls.
• Bariatric surgery appeared to be associated with a decreased risk for obesity-related cancer in women (HR, 0.76).
• There was a decreased risk for both obesity-related cancer (HR, 0.74) and CVD (HR, 0.82) in patients who underwent gastric bypass.

IN PRACTICE:

“The findings from this study suggest a limited role of bariatric surgery in older patients for the prevention of obesity-related cancer or cardiovascular disease,” the authors wrote, noting that this “may be explained by the poorer weight loss and resolution of comorbidities observed in patients who underwent surgery at an older age.”

SOURCE:

The study, with first author Peter Gerber, MD, PhD, Department of Surgery, Capio St Göran’s Hospital, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Data on smoking status and body mass index were not available. The observational design limited the ability to draw causal inferences. The null association between bariatric surgery and outcomes may be due to limited power.

DISCLOSURES:

The study was funded by the Swedish Society of Medicine. The authors reported no conflicts of interest.

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

TOPLINE:

For older adults with obesity, bariatric surgery does not appear to significantly reduce the risk for obesity-related cancer and cardiovascular disease (CVD), as it does in younger adults.

METHODOLOGY:

• Bariatric surgery has been shown to decrease the risk for obesity-related cancer and CVD but is typically reserved for patients aged < 60 years. Whether the same holds for patients who undergo surgery at older ages is unclear.
• Researchers analyzed nationwide data from three countries (Denmark, Finland, and Sweden) to compare patients with no history of cancer or CVD and age ≥ 60 years who underwent bariatric surgery against matched controls who received nonoperative treatment for obesity.
• The main outcome was obesity-related cancer, defined as a composite outcome of breast, endometrial, esophageal, colorectal, and kidney cancer. The secondary outcome was CVD, defined as a composite of myocardial infarction, ischemic stroke, and cerebral hemorrhage.
• Analyses were adjusted for diabetes, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease, kidney disease, and frailty.

TAKEAWAY:

• Of the 15,300 patients (66.4% women) included, 2550 underwent bariatric surgery (including gastric bypass in 1930) and 12,750 matched controls received nonoperative treatment for obesity.
• During a median 5.8 years of follow-up, 658 (4.3%) people developed obesity-related cancer and 1436 (9.4%) developed CVD.
• Bariatric surgery in adults aged ≥ 60 years was not associated with a reduced risk for obesity-related cancer (hazard ratio [HR], 0.81) or CVD (HR, 0.86) compared with matched nonoperative controls.
• Bariatric surgery appeared to be associated with a decreased risk for obesity-related cancer in women (HR, 0.76).
• There was a decreased risk for both obesity-related cancer (HR, 0.74) and CVD (HR, 0.82) in patients who underwent gastric bypass.

IN PRACTICE:

“The findings from this study suggest a limited role of bariatric surgery in older patients for the prevention of obesity-related cancer or cardiovascular disease,” the authors wrote, noting that this “may be explained by the poorer weight loss and resolution of comorbidities observed in patients who underwent surgery at an older age.”

SOURCE:

The study, with first author Peter Gerber, MD, PhD, Department of Surgery, Capio St Göran’s Hospital, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Data on smoking status and body mass index were not available. The observational design limited the ability to draw causal inferences. The null association between bariatric surgery and outcomes may be due to limited power.

DISCLOSURES:

The study was funded by the Swedish Society of Medicine. The authors reported no conflicts of interest.

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

TOPLINE:

MADRID — Elevated interleukin (IL) 6 levels are associated with an increased risk for obesity-related cancers in patients newly diagnosed with type 2 diabetes (T2D), potentially enabling the identification of higher-risk individuals through a simple blood test.

METHODOLOGY:

• T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
• Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
• They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
• At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.

TAKEAWAY:

• Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
• Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
• The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
• The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.

IN PRACTICE:

“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.

SOURCE:

The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

LIMITATIONS:

No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.

DISCLOSURES:

The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

MADRID — Elevated interleukin (IL) 6 levels are associated with an increased risk for obesity-related cancers in patients newly diagnosed with type 2 diabetes (T2D), potentially enabling the identification of higher-risk individuals through a simple blood test.

METHODOLOGY:

• T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
• Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
• They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
• At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.

TAKEAWAY:

• Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
• Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
• The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
• The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.

IN PRACTICE:

“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.

SOURCE:

The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

LIMITATIONS:

No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.

DISCLOSURES:

The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

MADRID — Elevated interleukin (IL) 6 levels are associated with an increased risk for obesity-related cancers in patients newly diagnosed with type 2 diabetes (T2D), potentially enabling the identification of higher-risk individuals through a simple blood test.

METHODOLOGY:

• T2D is associated with an increased risk for obesity-related cancers, including breast, renal, uterine, thyroid, ovarian, and gastrointestinal cancers, as well as multiple myeloma, possibly because of chronic low-grade inflammation.
• Researchers explored whether the markers of inflammation IL-6, tumor necrosis factor alpha (TNF-alpha), and high-sensitivity C-reactive protein (hsCRP) can serve as predictive biomarkers for obesity-related cancers in patients recently diagnosed with T2D.
• They identified patients with recent-onset T2D and no prior history of cancer participating in the ongoing Danish Centre for Strategic Research in Type 2 Diabetes cohort study.
• At study initiation, plasma levels of IL-6 and TNF-alpha were measured using Meso Scale Discovery assays, and serum levels of hsCRP were measured using immunofluorometric assays.

TAKEAWAY:

• Among 6,466 eligible patients (40.5% women; median age, 60.9 years), 327 developed obesity-related cancers over a median follow-up of 8.8 years.
• Each SD increase in log-transformed IL-6 levels increased the risk for obesity-related cancers by 19%.
• The researchers did not find a strong association between TNF-alpha or hsCRP and obesity-related cancers.
• The addition of baseline IL-6 levels to other well-known risk factors for obesity-related cancers improved the performance of a cancer prediction model from 0.685 to 0.693, translating to a small but important increase in the ability to predict whether an individual would develop one of these cancers.

IN PRACTICE:

“In future, a simple blood test could identify those at higher risk of the cancers,” said the study’s lead author in an accompanying press release.

SOURCE:

The study was led by Mathilde D. Bennetsen, Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark, and published online on August 27 as an early release from the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

LIMITATIONS:

No limitations were discussed in this abstract. However, the reliance on registry data may have introduced potential biases related to data accuracy and completeness.

DISCLOSURES:

The Danish Centre for Strategic Research in Type 2 Diabetes was supported by grants from the Danish Agency for Science and the Novo Nordisk Foundation. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

MADRID — Night owls — individuals with late chronotypes — may be at an increased risk for type 2 diabetes (T2D), beyond the risks conferred by an unhealthy lifestyle, research presented at the annual meeting of the European Association for the Study of Diabetes suggested.

In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.

“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.

“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”

“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”

The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.

Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.

During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.

Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm² more visceral fat, and 14% more liver fat.
 

Body Clock Out of Sync?

“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.

“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”

Might trying to adjust chronotype earlier in life have an effect on risk?

“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”

Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.

“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”

Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”

Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”

Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.

“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.

“However environmental factors and family history can play an important role too,” he added.

Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.

No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.

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

MADRID — Night owls — individuals with late chronotypes — may be at an increased risk for type 2 diabetes (T2D), beyond the risks conferred by an unhealthy lifestyle, research presented at the annual meeting of the European Association for the Study of Diabetes suggested.

In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.

“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.

“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”

“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”

The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.

Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.

During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.

Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm² more visceral fat, and 14% more liver fat.
 

Body Clock Out of Sync?

“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.

“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”

Might trying to adjust chronotype earlier in life have an effect on risk?

“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”

Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.

“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”

Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”

Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”

Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.

“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.

“However environmental factors and family history can play an important role too,” he added.

Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.

No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.

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

MADRID — Night owls — individuals with late chronotypes — may be at an increased risk for type 2 diabetes (T2D), beyond the risks conferred by an unhealthy lifestyle, research presented at the annual meeting of the European Association for the Study of Diabetes suggested.

In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.

“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.

“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”

“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”

The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.

Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.

During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.

Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm² more visceral fat, and 14% more liver fat.
 

Body Clock Out of Sync?

“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.

“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”

Might trying to adjust chronotype earlier in life have an effect on risk?

“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”

Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.

“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”

Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”

Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”

Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.

“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.

“However environmental factors and family history can play an important role too,” he added.

Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.

No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.

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

Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.

As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”

For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)

“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.

The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.

And there’s the rub.
 

‘Only Two Different Doses’

Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.

“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.

“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”

If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”

Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”

And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”

A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”

But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”

In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”

The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
 

Protection From Compounders?

According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”

Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.

Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”

But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.

Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”

“For 20 months now,” he continued, “compounders have been a lifeline for many patients, filling prescriptions for compounded tirzepatide injection at a time when the FDA-approved drug has been in shortage. We’ll be eager to see whether Lilly’s direct-to-patient approach actually works.”

Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”

Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.

A version of this article appeared on Medscape.com.

Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.

As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”

For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)

“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.

The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.

And there’s the rub.
 

‘Only Two Different Doses’

Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.

“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.

“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”

If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”

Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”

And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”

A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”

But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”

In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”

The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
 

Protection From Compounders?

According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”

Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.

Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”

But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.

Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”

“For 20 months now,” he continued, “compounders have been a lifeline for many patients, filling prescriptions for compounded tirzepatide injection at a time when the FDA-approved drug has been in shortage. We’ll be eager to see whether Lilly’s direct-to-patient approach actually works.”

Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”

Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.

A version of this article appeared on Medscape.com.

Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.

As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”

For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)

“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.

The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.

And there’s the rub.
 

‘Only Two Different Doses’

Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.

“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.

“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”

If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”

Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”

And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”

A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”

But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”

In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”

The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
 

Protection From Compounders?

According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”

Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.

Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”

But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.

Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”

“For 20 months now,” he continued, “compounders have been a lifeline for many patients, filling prescriptions for compounded tirzepatide injection at a time when the FDA-approved drug has been in shortage. We’ll be eager to see whether Lilly’s direct-to-patient approach actually works.”

Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”

Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.

A version of this article appeared on Medscape.com.