Coverage of the Endocrine Society's 2021 Annual Meeting

ENDO 2021

Underlining the importance of quality sleep to overall health, new research from Northwestern University suggests patients with 

 who experienced frequent sleep disturbances were 87% more likely to die than those with neither in the next 9 years.

An analysis of data from the UK Biobank cohort, results suggest frequent sleep disturbances and diabetes alone were associated with a 12% and 67% increase in risk of all-cause mortality, respectively, but the combination of both resulted in an 87% increase in risk of mortality over 8.9 years of follow-up.

"Diabetes alone was associated with a 67% increased risk of mortality. However, the mortality for participants with diabetes combined with frequent sleep problems was increased to 87%. In other words, it is particularly important for doctors treating people with diabetes to also investigate sleep disorders and consider treatments where appropriate,” said senior investigator Kristen Knutson, PhD, Associate Professor of Neurology and Preventive Medicine at Northwestern University Feinberg School of Medicine, 

With an interest in expanding the current knowledge base related to associations between diabetes, sleep disturbances, and mortality, Knutson and a team of colleagues from Northwestern’s Center for Circadian and Sleep Medicine and the University of Surrey designed the present study as an analysis of data from within the UK Biobank cohort. Using patients with full information related to sleep data and clinical characteristics, investigators identified a final cohort of 487,728 participants for inclusion in their analysis.

As part of the UK Biobank protocol, patients were asked about the frequency they experience sleep disturbances and responses were classified as never/rarely, sometimes, or usually. The primary outcomes of interest for analyses were mortality all causes and cardiovascular mortality.

For the purpose of analysis, investigators planned to conduct multiple analyses assessing sleep disturbances with risk of mortality. The first was adjusted for age and sex only while the second was fully adjusted for clinical factors and 11 different comorbidity variables.

Baseline analyses indicated 24.2% (n=118,217) reported never/rarely experiencing sleep disturbances while 47.8% (n=233,177) reported sometimes experiencing sleep disturbances and 28% (n=136,334) usually experiencing sleep disturbances. Overall, 69% of the study sample had no diabetes and report never/rarely experiencing sleep disturbances, 26% had frequent sleep disturbances but no diabetes, 3% had diabetes but no frequent sleep disturbances, and 2% had diabetes and frequent sleep disturbances.

Compared to those never/rarely experiencing sleep disturbances, patients with frequent sleep disturbances were older, had a higher BMI, slept less, and were more female, white, current smokers, and have depression or diabetes.

During the follow-up period, which lasted a mean of 8.9 years, 19,177 all-cause deaths and 3874 cardiovascular-specific deaths occurred among the study cohort. In the fully adjusted model, results indicated those with frequent sleep disturbances alone were at an 11% (HR, 1.11; 95% CI, 1.07-1.15) increased risk, those with diabetes alone were at a 67% (HR, 1.67; 95% CI, 1.57-1.76) increased risk, and those with both were at an 87% (HR, 1.87; 95% CI, 1.75-2.01) increased risk of all-cause mortality. Investigators also noted results suggested presence of sleep disturbances and diabetes was associated with a 12% (HR, 1.12; 95% CI, 1.04-1.22) increase in risk of mortality compared to patients with diabetes and no frequent sleep disturbances.

When assessing cardiovascular mortality, results indicated diabetes alone was associated with a 2-fold increase in risk (HR, 2.04; 95% CI, 1.84-2.27) while diabetes and frequent sleep disturbances were associated with further increased risk (HR, 2.11; 95% CI, 1.85-2.40). However, investigators pointed out no significant difference for cardiovascular mortality was observed for those with diabetes and frequent sleep disturbances versus those with diabetes and no frequent sleep disturbances (HR, 1.03; 95% CI, 0.89-1.20).

"The question asked when the participants enrolled does not necessarily distinguish between insomnia and other sleep disorders, such as sleep apnea. Still, from a practical point of view it doesn't matter. Doctors should take sleep problems as seriously as other risk factors and work with their patients on reducing and mitigating their overall risk,” added lead investigator Malcom von Schantz, PhD, Professor of Chronobiology from the University of Surrey, in the aforementioned statement.

Associations between sleep disturbances, diabetes and mortality in the UK Biobank cohort: A prospective population-based study,

Articles

An analysis of data from nearly 500k patients suggests patients with diabetes experiencing frequent insomnia were at an 87% increased risk of all-cause mortality compared to those with neither sleep disturbances nor diabetes. 

Study Underlines Importance of Quality Sleep in Patients with Diabetes

A man in his early 30’s is brought to the emergency department for vomiting. Medics state she said he has been drinking and often forgetting to take his insulin and his Jardiance. Over the past few hours, he vomited multiple times and she saw some blood and proceeded called 911. The patient is alert but a bit giddy. He denies any fever, pain, melena, or other complaints.


Vital signs are normal except for a pulse of 110. Physical exam is otherwise normal except for the odor of alcohol and a bit of non-bloody emesis on his shirt

: normal except for a hemoglobin of 10.2 with macrocytic indices

: normal except for a gap of 21 and a glucose of 193

Our latest case report from Dr. Brady Pregerson features a man in his 30s presenting to the ED after drinking and admits to forgetting his insulin and poor adherence to other antidiabetes medication. Can you determine the correct diagnosis?

Endocrine Case Report: Vomiting and Drunk

New research from Edith Cowan University in Australia is providing evidence of the impact lifestyle intervention can have on the health of at-risk patient populations.

An analysis of data from participants within the Australian Diabetes, Obesity, and Lifestyle Study, results indicate patients consuming 2 or more servings of fruit daily had 36% lower odds of developing 

 in the next 5 years than their counterparts who consumed half a serving or less daily.

"We found an association between fruit intake and markers of insulin sensitivity, suggesting that people who consumed more fruit had to produce less insulin to lower their blood glucose levels," said Nicola Bondonno, PhD, study lead investigator and Adjunct Lecturer at Edith Cowan University's Institute for Nutrition Research in Perth, Australia, 

. "This is important because high levels of circulating insulin can damage blood vessels and are related not only to diabetes, but also to high blood pressure, obesity, and heart disease.”

With the going prevalence of obesity and diabetes posing a significant public health burden, studies aimed at understanding avenues of mitigating this risk have received a greater emphasis in recent years. To learn more about dietary mechanisms related to fruit intake, Bondonno and a team of colleagues designed the current study as an analysis of data from participants within the Australian Diabetes, Obesity, and Lifestyle Study.

A national population-based survey of Australian adults, the study provided information related to more than 11,000 patients recruited between 1999-2000 and followed through 2012 for potential inclusion in their analyses. Using only those with complete data, including information from food frequency questionnaires, and who were free from diabetes at baseline, investigators identified a cohort of 7675 patients for inclusion in their analyses. Of note, 3518 patients had data available from the 12-year follow-up and 4674 had data available from the 5-year follow-up.

The overall study cohort had a mean age of 54±12 years at baseline, 45% were male, the mean BMI was 26.8±4.7 kg/m2, 48% had a physical activity level considered insufficient or sedentary, and the median total fruit intake was 162 (IQR, 95-283) g/day). Compared to those in the lowest quartile of total fruit intake, those with the greatest intake were more likely to be female, older, more physically active, less disadvantaged, have a higher level of education, and were less likely to be smokers.

Investigators used restricted cubic splines in logistic and linear regression models to evaluate associations fasting plasma glucose (FPG), 2-hour postload plasma glucose, updated homeostasis model assessment of insulin resistance of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and the presence of diabetes at the 5- and 12-year follow-ups.

Analysis of baseline data indicated total fruit intake was inversely associated with serum insulin and HOMA2-%β. Investigators also noted total fruit intake was positively associated with HOMA2-%S at baseline. Further analysis indicated those with moderate (quartile 3) total fruit intake had 36% lower odds of developing diabetes at 5 years. However, investigators pointed out associations with 12-year outcomes and total fruit intake were not statistically significant.

"We did not see the same patterns for fruit juice. These findings indicate that a healthy diet and lifestyle which includes the consumption of whole fruits is a great strategy to lower your diabetes risk,” added Bondonno, in a 

Associations Between Fruit Intake and Risk of Diabetes in the AusDiab Cohort

Journal of Clinical Endocrinology & Metabolism.

An analysis of food frequency questionnaire and biomarker data from more than 7000 adults indicates consumption of 2 or more servings of whole fruit per day was associated with 36% lower odds of developing diabetes in the next half-decade. 

Study Suggests 2 Servings of Fruit Per Day Cuts Odds of Developing Diabetes by 36%

The US Food and Drug Administration (FDA) has made history with the approval of subcutaneous semaglutide 2.4 mg (Wegovy) for chronic weight management in adults with obesity or overweight—making semaglutide 2.4 mg the first once-weekly GLP1-RA to receive such an approval and the first drug treatment to receive FDA approval for chronic weight management since 2014.

The approval, which is based on data from the phase 3 STEP Program, is for use in patients with a BMI of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 and indicates the treatment should be used in addition to a reduced calorie diet and increased physical activity.

“Today’s approval offers adults with obesity or overweight a beneficial new treatment option to incorporate into a weight management program,” said John Sharretts, MD, deputy director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research, 

. “FDA remains committed to facilitating the development and approval of additional safe and effective therapies for adults with obesity or overweight.”

With the STEP program demonstrating the safety and efficacy of semaglutide 2.4 mg in multiple patient populations with obesity or overweight, the FDA grantedapproval for the agent to Novo Nordisk, who received approval for the semagltudie 1 mg (Ozempic) for treatment in type 2 diabetes in 2017. With each of the 4 STEP trials providing evidence of the drug’s effects in more than 2600 patients with obese or overweight, many are hopeful the drug could help curb the growing obesity epidemic in the US.

Among patients without diabetes in the STEP program, use of semaglutide 2.4 mg was associated with an average weight loss of 17-18% that was sustained over 68 weeks. The most common adverse events seen with semaglutide 2.4 mg were nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, and indigestion.

Additionally, the FDA statement pointed out the prescribing information for semaglutide 2.4 mg contains a boxed warning to inform clinicians and patients about the potential risk of thyroid C-cell tumors and also noted the agent should not be used in patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

, Novo Nordisk expressed optimism about the promise of semaglutide 2.4 mg for chronic weight management and also pointed out they expect the agent to be available in the US in late June 2021.

“The approval of Wegovy™ in the US brings great promise to people with obesity. Despite the best efforts to lose weight, many people with obesity struggle to achieve and maintain weight loss due to physiological responses that favor weight regain,” said Martin Holst Lange, executive vice president, Development at Novo Nordisk. “The unprecedented weight loss for an anti-obesity medication marks a new era in the treatment of obesity, and we now look forward to making Wegovy™ available to people living with obesity in the US”.

This is a breaking news story and will be updated as more information becomes available.

The FDA has announced the approval of semaglutide 2.4 mg (Wegovy) for chronic weight management in patients with obesity or overweight—the first drug to receive such an approval from the FDA in more than half a decade.

Semaglutide (Wegovy) Approved for Chronic Weight Management in Patients with Obesity or Overweight

New research from UC Davis School of Medicine indicates a single hospitalization for hypoglycemia or hyperglycemia was linked to increased risk for developing dementia among older patients with 

A longitudinal cohort study spanning nearly 2 decades, results suggest hospitalization for either severe hypoglycemia or hyperglycemia was associated with significant increase in risk for developing dementia while patients who experienced both had a more than 6-fold greater risk of developing dementia.

“People with type 1 diabetes are living longer than before, which may place them at risk of conditions such as dementia. If we can potentially decrease their risk of dementia by controlling their blood sugar levels, that could have beneficial effects for individuals and public health overall,” said study author Rachel A. Whitmer, PhD, of the University of California Davis School of Medicine in Sacramento, 

With advances in diabetes management extending the life expectancies of patients with type 1 diabetes, identification of events of factors increasing risk of dementia among these patients could improve quality of life and alleviate potential burden on healthcare systems.

Spurred by this and previous data linking severe glycemic events to increased dementia risk in patients with type 2 diabetes, Whitmer and a team of colleagues sought to determine whether such an association exists among older patients with type 1 diabetes. To fill this apparent knowledge gap, investigators designed the current study as a longitudinal study of patients within the Kaiser Permanente Northern California (KPNC) Diabetes Registry.

For the purpose of analysis, investigators identified patients within the registry from 1996-2013 aged 50 years and older who had type 1 diabetes, filled insulin prescriptions during the study period, and did not fill prescriptions for any other hypoglycemic agents. Once considered eligible for inclusion, exposure and covariate status were ascertained from start of the study period for up to 365 days after the date of eligibility. After this period, patients were entered into the cohort and follow-up began.

Patients were followed for up to 18 years or until a dementia diagnosis, death, lapse in KPNC membership for more than 90 days, or the end of the study period, which was September 30, 2015. Severe glycemic events were identified through use of ICD codes and dementia risk was calculated using Cox proportional hazard models adjusted for age, sex, race/ethnicity, HbA1c, depression, stroke, and presence of nephropathy.

A total of 2821 patients meeting eligibility criteria were included in the study. The mean follow-up time for the study population was 6.9 (SD, 5.0) years, the mean age at cohort entry was 56.5 (SD, 7.8) years, 48% were female, and 81% were White.

At cohort entry, 398 (14.1%), 355 (11.9%), and 87 (3.1%) patients experienced a severe hypoglycemic event, a severe hyperglycemic event, and both, respectively. Overall, 153 (5.4%) of patients received a diagnosis of dementia during the study period.

Compared to those without a severe hypoglycemic event, those experiencing hypoglycemic events were at a 66% increased risk of developing dementia (HR, 1.66; 95% CI, 1.09-2.53). Compared to those without a severe hyperglycemic event, those experiencing hyperglycemic events were at a more than 2-fold increased risk of developing dementia (HR, 2.11; 95% CI, 1.24-3.59). Among the subgroup of patients experiencing both severe hypoglycemic and severe hyperglycemic events, the risk of developing dementia was more than 6 times greater than those who experienced neither (HR, 6.20; 95% CI, 3.02-12.70).

“Our findings suggest that exposure to severe glycemic events may have long-term consequences on brain health and should be considered additional motivation for people with diabetes to avoid severe glycemic events throughout their lifetime,” Whitmer said.

Association of Type 1 Diabetes and Hypoglycemic and Hyperglycemic Events and Risk of Dementia

A look at more than 2800 older patients with type 1 diabetes indicates experiencing severe glycemic events was linked to an increased risk of developing dementia.

Severe Glycemic Events Linked to Development of Dementia in Older Patients with Type 1 Diabetes

A retrospective cohort study of more than 41,000 insulin-treated patients with diabetes suggests patients with type 1 and type 2 diabetes could benefit from the initiation of real-time continuous glucose monitoring (CGM).

Results of the study indicate use of CGM in patients with diabetes resulted in significant improvements in HbA1c and reductions in emergency department visits and hospitalizations for hypoglycemia, but no significant changes in emergency department visits or hospitalizations for hyperglycemia or for any reason.

"The improvement in blood sugar control was comparable to what a patient might experience after starting a new diabetes medication," said the study's lead author Andrew J. Karter, PhD, a senior research scientist with the Kaiser Permanente Northern California Division of Research, 

With an interest in describing the clinical outcomes associated with CGM initiation in patients with diabetes, Karter and colleagues from the Permanente Medical Group designed a retrospective cohort study to compare use and nonuse in patients with type 1 and type 2 diabetes receiving care at Kaiser Permanente Northern California from 2015-2018. In total, 41,753 patients, including 5673 with type 1 diabetes and 36,080 with type 2 diabetes, were identified for inclusion.

Major eligibility criteria for the study included maintaining continuous health plan membership for 12 months before and after baseline, having pharmacy benefits during the 12 months before baseline, having at least 1 pharmacy dispensing of glucose monitoring test strips during the 12 months before baseline, having at least 1 pharmacy dispensing of insulin during the 6 months before baseline, not using CGM between January 1, 2014, and baseline. A total of 10 endpoints were used as outcomes of interest in the trial and were measured during the 12 months before and 12 months after baseline.

Of the 41,753 patients included in the study, 3806 initiated real-time CGM and 37,947 patients were considered noninitiators. Among the 3806 who initiated real-time CGM use, 3462 had type 1 diabetes and 344 had type 2 diabetes. Among the 37,947 non initiators, 2211 had type 1 diabetes and 35,736 had type 2 diabetes.

Compared to noninitiators, those who initiated real-time CGM had similar mean HbA1c, higher rates of hypoglycemia and hyperglycemia, higher predicted risk of hypoglycemia, and were more likely to have been dispensed glucagon, insulin pen or pump, and long- or rapid-acting insulin. Of note, all patients with type 1 diabetes and 97% with type 2 diabetes were using basal-bolus insulin.

Upon analysis, investigates found mean HbA1c declined from 8.17% to 7.76% among real-time CGM initiators and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, -0.40%; 95% CI, -0.48 to -0.32%; 

 <.001). Additionally, rates of hypoglycemia declined from 5.1% to 3.0% among CGM initiators and increased from 1.9% to 2.3% among noninitiators (difference-in-differences estimate, -2.7%; 95% CI, -4.4 to -1.1%; 

Investigators noted statistically significant differences in adjusted net changes in the proportion of patients with an HbA1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; 

<.001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2 to 16.1%; 

 <.001), and higher than 9% (adjusted difference-in-differences estimate, -7.1%; 95% CI, -9.5 to -4.6%; 

<.001). Investigators also pointed out a statistically significant difference in the number of outpatient visits (adjusted difference-indifferences estimate, -0.4; 95% CI, -0.6 to -0.2; 

<.001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; 

<.001), but no significant difference was observed in regard to rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason.

"We now need to determine whether there are other patients who might also benefit, even if they don't meet all of the Medicare criteria. The newest technology isn't always better for everybody. We need to identify the people who are most likely to benefit,” added Richard Dlott, MD, an endocrinologist and the medical director of population care for The Permanente Medical Group, in the aforementioned statement.

Association of Real-time Continuous Glucose Monitoring With Glycemic Control and Acute Metabolic Events Among Patients With Insulin-Treated Diabetes

A retrospective look at patients who initated real-time CGM versus noninitiators indicates CGM use resulted in significant reductions in HbA1c and also reduced the number of outpatient and telephone visits among patients with type 1 diabetes and type 2 diabetes.

Real-Time CGM Use Reduces HbA1c, Outpatient Visits in Patients with Type 1 and Type 2 Diabetes

Results of a randomized, open-label trial examining use of the Dexcom G6 Continuous Glucose Monitoring System supports the incorporation of continuous glucose monitoring (CGM) into disease management for patients with type 2 diabetes.

The study, which randomized more than 150 patients from 15 US medical centers, concluded use of CGM resulted in significantly lower HbA1c and increased time in target range at 8 months when compared to traditional blood glucose monitoring in patients with type 2 diabetes treated with basal insulin without prandial insulin.

Conducted by the MOBILE study group in conjunction with the Jaeb Center for Health Research, the current trial sought to expand on the current knowledge base surrounding CGM use in patients with type 2 diabetes, specifically those using basal insulin without prandial insulin. Of note, the MOBILE study group also published a similar study in 

assessing the impact of CGM versus traditional glucose monitoring in patients with type 1 diabetes in June 2020.

The trial was created with a multicenter, randomized, open-label, parallel-group design and randomized 175 patients in a 2:1 ratio to CGM or traditional blood glucose monitoring. Enrollment for the study was performed between July 30, 2018 and October 30, 2019 and follow-up was completed on July 7, 2020.

All patients included in the trial were not receiving care from an endocrinologist for their diabetes and were recruited from primary care practices. Eligibility criteria for the trial included being at least 30 years of age, locally measured HbA1c level of 7.8-11.5%, self-reported blood glucose monitoring testing 3 or more times per week, and available slitty of a smartphone compatible with a CGM device. Patients included in the trial could be using any other antidiabetes medications with the exception of prandial insulin.

Patients in the study were required to use a CGM that recorded glucose concentrations not visible to participants for up to 10 days. To be included in the trial, patients needed to have a minimum of 168 hours of glucose values available for analysis.

In total, 116 patients were randomized to CGM and 59 were randomized to traditional blood glucose monitoring. The overall study cohort had a mean HbA1c of 9.1% (SD, 0.9%), a mean age of 57 (SD, 9) years, 50% were women, 53% were racial/ethnic minority individuals, and 94% completed the trial.

Of note, original calculations indicated a sample size of 207 was needed to achieve at least 85% power to detect a difference in mean HbA1c level. Investigators pointed out recruitment was discontinued after October 2019 after it became apparent the study completion rate was higher than project—this was a joint decision between the coordinating center director and the study sponsor, which was Dexcom Inc.

The primary outcome of interest for the study was HbA1c level at 8 months. Secondary outcomes of interest included CGM-measured time in target glucose range of 70-180 mg/dL, time with glucose levels exceeding 250 mg/dL, and mean glucose level at 8 months.

Among patients in the CGM arm of the trial, the mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months. Among patients in the control arm, mean HbA1c decreased from 9.0% at baseline to 8.4% at 8 months (adjusted difference, -0.4% [95% CI, -0.8 to -0.1%]; 

When assessing secondary outcomes, results indicated those in the CGM group achieved a greater mean percentage of CGM measured time in target glucose range (59% vs 43%; adjusted difference, 15% [95% CI, 8-23%]; 

<.001), lower mean percentage of time above 250 mg/dL (11% vs 27%; adjusted difference, -16% [95% CI, -21 to -11%]; 

<.001), and lower means of the mean glucose values (179 mg/dL vs 206 mg/dL; adjusted difference, -26 mg/dL [95% CI, -41 to -12]; 

<.001) when compared to those using traditional blood glucose monitoring.

When assessing safety, investigators identified a severe hypoglycemic event in 1 patient from the CGM arm and 1 patient from the traditional blood glucose monitoring group. Additionally, 1 occurrence of diabetic ketoacidosis was observed in the CGM group.

, Monica Peek, MD, MPH, and Celeste Thomas, MD, MS, both of the University of Chicago Medicine, remarked on the promise of CGM in type 2 diabetes demonstrated in this trial and an additional retrospective study simultaneously published in 

“The clinical trial by Martens et al demonstrated the promise of using CGM in primary care settings, where most patients with type 2 diabetes receive their care. This trial, in which study clinicians met with trial participants during in-person clinic visits followed by virtual visits, provides a model that could be replicated or modified in many primary care practices throughout the US,” wrote Peek and Thomas.

Effect of Continuous Glucose Monitoring on Glycemic Control in Patients With Type 2 Diabetes Treated With Basal Insulin

A trial of more than 150 patients with type 2 diabetes using basal insulin without prandial insulin suggests CGM use among these patients could lower HbA1c and improve time in target range compared to traditional blood glucose monitoring.

MOBILE: CGM with Dexcom G6 Improves Glucose Control in Patients with Type 2 Diabetes Using Basal Insulin

An analysis of claims data from US-based patients is providing an overview of the impact diabetes status on patients with thyroid eye disease.

Results of the analysis, which were presented at the American Academy of Clinical Endocrinology’s 30th Annual Meeting (

), detail the impact of diabetes status on disease presentation and also on rates of disease complications.

“Our data suggest that TED may manifest differently in patients with and without diabetes mellitus. In patients with diabetes mellitus (both type 1 and 2), proptosis was observed less often and eye muscle dysfunction observed more often as compared with TED patients without diabetes mellitus,” wrote investigators. “In addition, TED severity differed between TED patients with diabetes mellitus versus those without diabetes mellitus.”

Conducted by Lissa Padnick-Silver, PhD, and colleagues from Horizon Therapeutics, who owns the rights to teprotumumab (Tepezza), the AACE 2021 study was designed as an analysis of data from the Symphony database. Using this database, investigators hoped to identify patients with 1 or more ICD-9 codes for Graves’ orbitopathy and thyroid eye disease and enrolled within the databases for at least 2 years. The thyroid eye disease code algorithm for proptosis, diplopia, lid retraction, strabismus, exposure keratopathy, and optic neuropathy in patients with Graves orbitopathy.

For the purpose of analysis, patients were stratified based on presence/absence of diabetes codes and thyroid eye disease codes. Investigators also pointed out patients with sight-threatening thyroid eye disease, which was defined as 1 or more ON or exposure keratopathy codes, were identified and examined in a severity assessment.

Investigators identified a cohort of 51,220 patients with both Graves orbitopathy and thyroid eye disease. Among these patients, 5.1% had type 1 diabetes, 25.1% had type 2 diabetes, and the remaining 69.8% were considered nondiabetic. Compared to those without diabetes (51.4 years), patients type 1 diabetes (59.0 years) and type 2 diabetes (59.6 years) were older at time of first thyroid eye disease diagnosis.

Upon analysis, results indicated proptosis appeared to be less prevalent among patients with diabetes (T1D: 42%; T2D: 46% vs 59%), but an increased prevalence was seen for strabismus (25%; 23% vs 20%) and diplopia (39%; 38% vs 30%) was seen among patients with diabetes (

 for all <.001). Incidence of sight-threatening thyroid eye disease was more common among patients with type 1 (13%) and type 2 diabetes (13%) compared to those without diabetes (11%).

When examining sight-threatening codes separately, results indicated more patients with diabetes had ON codes (4%; 4% vs 3%; 

 for both <.003) but keratopathy was similar among the groups (10%; 9% vs 9%; 

=.304). Additionally, a similar proportion of patients with type 1 diabetes and those without diabetes had 1 or more code for thyroid eye disease surgery, but surgical rates were lower among those with type 2 diabetes (

Investigators noted multiple limitations within their study for clinicians or researchers to consider before overinterpretation of results.

“This study identified thyroid eye disease-related differences in patients with and without diabetes mellitus. Further exploration is warranted, particularly longitudinal analyses of thyroid eye disease presentation and progression in patients with and without diabetes mellitus,” wrote investigators.

Impact of Diabetes on Thyroid Eye Disease in US Patients: A Claims-Based Study

Analysis of claims data from the Symphony database offers clinicians greater insight into the impact of diabetes, both type 1 and type 2, on thyroid eye disease in US patients. 

Study Details Impact of Diabetes on Disease Presentation Among Patients with Thyroid Eye Disease

Data from a systematic review and meta-analysis performed by investigators at the Mackay Memorial Hospital in Taiwan provides a comprehensive overview of the risk of 

 in patients with thyroid cancer from current literature.

Using data from nearly 200,000 patients with thyroid cancer receiving thyroidectomy, investigators were able to shed light on the incidence of cardiovascular disease, atrial fibrillation (AF), and cardiovascular mortality among patients with thyroid cancer as a whole and based on whether or not they received treatment with radioactive iodine.

“To our knowledge, this study is the first meta-analysis to examine the association of thyroid cancer with cardiovascular disease. These results provide insights toward optimizing thyroid cancer strategies that should consider the potential harms and benefits during cancer treatment,” wrote study investigators.

Presented at the American Academy of Clinical Endocrinology’s 30th Annual Meeting (

) by Wen Hsuan Tsai, MD, the study was designed as a systematic review and meta-analysis with the intent of detailing the association between thyroid cancer and cardiovascular disease from literature available in the PubMed, Embase, and Cochrane Library databases from inception through November 25, 2020. For the purpose of analysis, investigators limited their review to prospective and retrospective studies and keywords used in their search of the aforementioned databases included thyroid cancer, AF, cardiovascular disease, and thyroxine.

The primary outcomes of interest for the analyses were incidence of cardiovascular disease, AF, and cardiovascular mortality among thyroid cancer compared to the general population and secondary outcomes included incidence of these outcomes among patients with and without radioactive iodine treatment.

In total, 9 studies met inclusion criteria. From these 9 studies, investigators obtained data related to 197,202 patients with thyroid cancer receiving thyroidectomy.

In a pair of studies, risk estimates indicated patients with thyroid cancer were at a 15% greater risk of cardiovascular disease than the general population (RR, 1.15; 95% CI, 1.10-1.21). In an analysis of 3 studies measuring incidence of AF, results suggested a significant difference in a fixed-effect model (RR, 1.37; 985% CI, 1.15-1.62) but no significant difference in the random effect model (RR, 1.47; 95% CI, 0.96-2.23) when compared to the general population.

When assessing cardiovascular mortality in a group of 3 studies, results indicated the association between cardiovascular mortality and thyroid cancer was insignificant (RR, 0.82; 95% CI, 0.66-1.01). Additionally, analysis of pooled data from 3 studies indicated there was no significant difference in risk of cardiovascular disease among patients based on whether they received RAI treatment after thyroidectomy (RR, 1.01; 95% CI, 0.81-1.26).

Association of thyroid cancer with cardiovascular disease, atrial fibrillation and cardiovascular-specific mortality: A systematic review and meta-analysis

A systematic review and meta-analysis presented at AACE 2021 details the risk of cardiovascular disease in patients with thyroid cancer who have undergone thyroidectomy. 

AACE 2021 Analysis Details Risk of Cardiovascular Disease, AFib, and CV Death in Thyroid Cancer Patients

This article was originally published on 


An analysis of data from nearly a dozen studies is providing insight into the relationship between various risk factors and risk of peripheral artery disease (PAD) in 

Presented by Martha Rosana, MD, of the Department of Internal Medicine at the University of Indonesia, at the American Academy of Clinical Endocrinology’s 30th Annual Meeting (

), results of the study detail the impact of increased age, increased duration of diabetes, and disease history can have on risk of PAD in patients with type 2 diabetes.

Led by Rosana and colleagues from the University of Indonesia, the current study was designed to provide clinicians and researchers with a comprehensive review of risk factors associated with incidence of PAD in patients with type 2 diabetes. With this in mind, investigators designed their study as a systematic review and meta-analysis of studies detailing incidence of PAD in populations with type 2 diabetes from major databases and other sources.

Risk factors of interest for the investigators’ analyses included age, sex, duration of diabetes, hypertension status, history of coronary artery disease (CAD) or stroke, obesity, HbA1c levels, eGFR, dyslipidemia, smoking status, and fibrinogen level.

For the purpose of analysis, investigators designed their study using the PRISMA standard and data obtained from the PubMed, MEDLINE, ProQuest, and EMBASE database. Their specific search sought to identify cohort or case-control studies reporting risk factors of PAD incidence among patient populations with type 2 diabetes mellitus.

From their search of databases, investigators identified 14,129 articles for possible inclusion in the systematic review and meta-analysis and 39 articles from other sources. After exclusion of duplicates and screening, 51 full-text articles were assessed for eligibility. Of these, 10 were included in the qualitative synthesis and 9 were included in the meta-analysis.

Among the articles assessed but that were ultimately excluded, the most common reason for exclusion was a different diagnosis criterion for PAD (n=13) followed by a different outcome measure (n=11), patient population did not have type 2 diabetes mellitus (n=5), and used the same subject as another study (n=5). All 10 studies included in the qualitative synthesis had a low risk of bias according to the 

 and included a total population of 73,834 patients with type 2 diabetes.

Upon analysis, investigators found being 70 years of age or older (OR, 3.44; 95% CI, 2.11-5.62), having diabetes for 5 years or more (OR, 1.81; 95% CI, 1.24-2.64), a history of CAD (OR, 1.55; 95% CI, 1.30-1.83), hypertension (OR, 1.43; 95% CI, 1.10-1.86), and elevated LDL-C (2.51; 95% CI, 1.38-4.58) were associated with an increase in odds of developing PAD. Investigators noted all evidence had a grade of moderate certainty.

Risk Factors of Peripheral Arterial Disease in Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-analysis

A systematic review and meta-analysis presented at AACE 2021 shed light on risk factors associated with increased odds of developing peripheral artery disease among patients with type 2 diabetes. 

Age, Disease History Play Role in Developing Peripheral Artery Disease in Patients with Diabetes

New research from the University of Glasgow suggests the concept of 

 could be misleading, as data indicates these patients were still at increased risk of obesity-related adverse health outcomes.

An analysis of more than 380,000 individuals with a median follow-up of 11.2 years, results indicate patients considered to have metabolically healthy obesity were 4.3 times more likely to develop 

, 76% more likely to develop heart failure, and 18% more likely to suffer a heart attack or stroke during the follow-up period compared to their metabolically healthy counterparts without obesity.

"People with metabolically healthy obesity are not 'healthy' as they are at higher risk of heart attack and stroke, heart failure, and respiratory diseases compared with people without obesity who have a normal metabolic profile,” wrote investigators.

With the obesity epidemic continuing to swell, greater emphasis on research into different phenotypes of obesity could improve the existing knowledge base and care of patients. With this in mind, Frederick Ho, PhD, and colleagues from the Institute of Health and Wellbeing at the University of Glasgow designed the current study to assess associations of metabolically healthy obesity and obesity-related outcomes using data from the UK Biobank cohort.

A population-based prospective cohort study of more than 500,000 participants, the UK Biobank cohort contained data related to 381,363 participants who were not underweight and had complete data related to metabolic profile for inclusion in their analysis. Investigators planned to use Cox proportional hazards models to assess associations between metabolically healthy outcomes and health outcomes.

For the purpose of analysis, metabolically healthy obesity was defined as having a BMI of 30 kg/m

 or more and at least 4 of the 6 metabolically healthy criteria. These 6 markers used to define metabolic health were blood pressure, CRP, triglycerides, LDL-C, HDL-C, and HbA1c. Health outcomes of interest included incident diabetes and incident and fatal atherosclerotic cardiovascular disease (ASCVD), heart failure, and respiratory diseases.

Of the 381,363 participants included in the study, 54.7% (n=208,625) were considered metabolically healthy and of normal weight, 9.2% (n=35,103) had metabolically healthy obesity, 20.5% (78,259) were metabolically unhealthy without obesity, and 15.6% (n=59,376) were metabolically unhealthy with obesity.

In fully adjusted models, those with metabolically healthy obesity had a higher rates of incident heart failure (1.60; 95% CI, 1.45-1.75) and respiratory disease (HR, 1.20; 95% CI, 1.16-1.25) compared to those who were not obese at baseline. However, investigators noted this increased rate was not observed for ASCVD. Further analysis indicated these associations were generally weaker for fatal outcomes and only reached significance for all-cause (HR, 1.12; 95% CI, 1.04-1.21) and heart failure (HR, 1.44; 95% CI, 1.09-1.89) mortality rates.

Compared to those who were metabolically healthy without obesity, those with metabolically healthy obesity had greater rates of incident diabetes (HR, 4.32; 95% CI, 3.83-4.89), ASCVD (HR, 1.18; 95% CI, 1.10-1.27), heart failure (HR, 1.76; 95% CI, 1.61-1.92), respiratory diseases (HR, 1.28; 95% CI, 1.24-1.33) and all-cause mortality (HR, 1.22; 95% CI 1.14-1.31). Investigators also pointed out a subgroup analysis comparing those who transitioned from metabolically healthy obesity to metabolically unhealthy obesity during the follow-up to those considered metabolically healthy and of normal weight indicated these patients experienced greater rates of incident ASCVD (HR, 2.46; 95% CI, 1.12-5.41) and all-cause mortality (HR, 3.07; 95% CI, 1.44-6.56).

"Weight management could be beneficial to all people with obesity irrespective of their metabolic profile. The term 'metabolically healthy obesity' should be avoided in clinical medicine as it is misleading, and different strategies for defining risk should be explored,” wrote investigators.

Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants,

Data from the UK Biobank cohort details the increased risk of adverse health outcomes, including the development of diabetes and heart failure, among patients considered to have metabolically healthy obesity. 

'Metabolically Healthy' Obesity Still Puts Patients at Increased Risk of Adverse Health Outcomes

Findings from a recent systematic review of more than a dozen studies are highlighting the potential of topical treatments for patients with diabetic retinopathies. 

A team led by Mikkel Thagaard, MD, Department of Ophthalmology, Odense University Hospital, conducted a review of 19 studies, all of which evaluated patients with diabetic retinopathy and/or diabetic macular edema. The goal of their analysis was to determine whether topical treatments could have an effect on disease change or progression.

Thagaard and colleagues utilized PubMed, Embase, and Scopus to search for relevant and appropriate studies. All eligible and evaluated studies were a mix of randomized clinical trials and non-randomized trials and were heterogenous in target population, interventions, and outcome measure.

Of those included in the meta-analysis, 13 investigated topical eye drop use in DME populations. Further, 3 of those studies were randomized clinical trials, which generally showed favorable outcomes associated with treatment.

For example, Ohira et al (2015)—which compared 1.5% dexamethasone y-cyclodextrin nanoparticles (DexNP) with triamcinolone acetonide injection in patients with central DM— reported that topical treatment was associated with an increase in best-corrected visual acuity (BVCA) and decrease in macular thickness.

Gupta et al (2014) showed that BVCA increased in patients who received 0.2% brimonidine and placebo. Foveal avascular zone (FAZ) decreased in area and diameter for treated patients.

However, results from Friedman et al (2015) indicated no change in BVCA and retinal volume between noncentral DME patients in both 0.1% nepafenac and placebo groups.

The remaining (non-randomized) clinical trials were variable in efficacy outcomes, some showing improvements in BCVA and others showing no change associated with various types of topical treatments.

Similarly, retinal thickness, volume, and foveal thickness (or other retinal outcomes in question) improved for retinopathy populations, while one study (Campochiaro et al) reported no change on OCT.

A total of 6 studies were evaluated that looked at efficacy of eye drops in patients with diabetic retinopathy. Of these studies, 4 were randomized clinical trials.

Mondal et al (2004) assessed 0.1% brimonidine (versus placebo) in patients with very mild non-proliferative diabetic retinopathy. As such, the investigators reported that BCVA improved in 60% of patients; progression of disease was not observed.

Simó et al (2019) showed that 0.2% brimonidine and 0.1% somatostatin in those with no, minimal, or mild non-proliferative diabetic retinopathy had no effect on BCVA but was associated with no worsening mfERG IT in patients with preexisting neurodegeneration.

Grauslund et al (2019) compared 0.2% brimonidine with 0.1% somatostatin and placebo in no - mild non-proliferative diabetic retinopathy. They did not report on visual outcomes but indicated the topical treatment was linked to an increase in central retinal arteriolar equivalent (CRAE) and central retinal venula equivalent (CRVE) in mild diabetic retinopathy.

And finally, Parravano et al (2020)—which enrolled patients with mild non-proliferative diabetic retinopathy with impaired retinal sensitivity—demonstrated an association between 0.05% cyanocobalamin treatment and no worsening of retinal sensitivity and deep vessel densitiy.

Patients with mild non-proliferative diabetic retinopathy in the non-randomized clinical trials experienced no improvement in BCVA with F2-alphablocker and NSAID as well as with carbonic anhydrase inhibitor. F2-alphablocker treatment led to reductions in arteriolar calibre.

Thagaard and colleagues indicated that while overall observations from these studies showed promise for topical eye drops in mild diabetic retinopathy and DME, more research—particularly randomized clinical trials and with longer follow-up periods—are warranted.

“Hopefully, the future will reveal further clinical trials and advances in eye drop treatment not only in diabetic retinopathy but also in other ocular diseases affecting the retina and posterior segment such as age-related macular degeneration, retinitis pigmentosa, and glaucoma,” they wrote.

The study, "Topical treatment of diabetic retinopathy: a systematic review," was published online in 

A systematic review details the impact of topical agents for the treatment of diabetes-related ophthalmic conditions, such as diabetic macular edema and diabetic retinopathy. 

Topical Treatments Show Promise in Diabetic Eye Diseases

An analysis of nearly 175k patients with 

 associated with the common hormonal endocrine disorder.

Results of the analysis suggest young women with PCOS were at an increased risk of adverse cardiovascular events and also indicate weight and diabetes status stood out as potentially modifiable risk factors for this association.

“This is the largest study to confirm an increased incidence of major cardiovascular morbidity in patients with PCOS and emphasizes the importance of recognizing the disorder as a higher-risk vascular condition,” wrote investigators.

With PCOS the most common endocrine condition impacting young women and the relationship between PCOS and cardiovascular risk unclear, a UK-based team of investigators sought to explore these potential associations using data from the Clinical Practice Research Datalink Aurum database. With more than 200,000 women with PCOS included in the database from 1998-2017, investigators identified a cohort of 181,916 meeting eligibility criteria for inclusion in their matched analyses.

All patients included in the study were at least 18 years of age or older and were matched in a 1:1 ratio to a set of non-PCOS controls based on age, BMI category, and primary care practice. Investigators pointed out patients with a history of myocardial infarction, stroke, angina, or revascularization were excluded from survival analyses.

The primary outcome of interest for the study was time to major adverse cardiovascular event (MACE), which was defined as myocardial infarction, stroke, angina, revascularization, and cardiovascular mortality. The secondary outcomes of interest were individual components of the composite MACE endpoint.

Of the 181,916 deemed eligible for inclusion, 174,660 were matched to non-PCOS controls. The median follow-up time for patients with PCOS was 3.83 (IQR, 1.89-7.78) years and 3.00 (IQR, 1.37-6.36) for controls. Investigators noted significant differences in presence of extreme obesity (4.65% vs 3.12%) were evident at baseline between the cohorts and women with PCOS were also more to have a higher Charlson Index score and higher blood pressure.

Analysis indicated crude rates of the composite endpoint, MI, stroke, angina, revascularization, and cardiovascular mortality were 82.7, 22.7, 27.4, 32.8, 10.5, and 6.97 per 100,000 patient-years, respectively, for women with PCOS and 64.3, 15.9, 25.7, 19.8, 7.13, and 7.75 per 100,000 patient-years, respectively, for matched controls. In adjusted models, women with PCOS were at 26% greater risk of the composite outcome (HR, 1.26; 95% CI, 1.13-1.41) and 38%, 60%, and 50% greater risk for myocardial infarction (HR, 1.38; 95 CI, 1.11-1.72), angina (HR, 1.50; 95% CI, 1.32-1.94), and revascularization (HR, 1.50; 95% CI, 1.08-2.07), respectively, when compared to non-PCOS controls.

In time-dependent models, results suggested weight gain (HR, 1.01; 95% CI, 1.00-1.01), prior type 2 diabetes (HR, 2.40; 95% CI, 1.76-3.30), and social deprivation (HR, 1.53; 95% CI, 1.11-2.11) were factors associated with increased risk of progression to the composite endpoint.

“Our study demonstrates that young women with a diagnosis of PCOS have an increased incidence of major cardiovascular events, whether captured as a composite outcome or as myocardial infarction, angina and revascularization individually,” wrote investigators. “High-quality longitudinal studies are now needed to understand any effect of disease phenotype and ethnicity on risk, and whether screening strategies with targeted intervention can lead to improved cardiovascular outcomes.”

Women with Polycystic Ovary Syndrome have an increased risk of major cardiovascular events: a population study

Journal of Clinical Endocrinology and Metabolism.

A comparison of women with PCOS to matched controls indicates women with PCOS were at a 26% greater risk of experiencing major adverse cardiovascular events than their counterparts without polycystic ovary syndrome. 

Women with Polycystic Ovary Syndrome at Increased Risk of Cardiovascular Disease Events

Despite practice-changing advances in technology and pharmacy, new research from the Johns Hopkins Bloomberg School of Public Health suggests rates of glycemic control among 

A cross-sectional analysis of NHANES data paints a grim picture related to rates of patients with diabetes achieving goals for glycemic, blood pressure, and lipid control. 

'Metabolically Healthy' Obesity Still Puts Patients at Increased Risk of Adverse Health Outcomes

Topical Treatments Show Promise in Diabetic Eye Diseases

Women with Polycystic Ovary Syndrome at Increased Risk of Cardiovascular Disease Events

Despite Advances, Rates of Glycemic Control Backsliding in Past Decade

Evaluating Subsequent Fracture Risk in Aging Women with Traumatic Fractures