Featured Science from ENDO 2020

[madman]

Thyroid hormone use may raise death risk in older adults

Thyroid hormone replacement therapy in older adults is associated with a higher risk of death compared with no treatment, a large study finds. The study results were accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.



OR18-05: Thyroid Hormone Use and Relative Survival Among the BLSA Cohort Jennifer

Background: Thyrotropin (TSH) levels are higher on average and vary more widely among older adults even in the absence of frankly abnormal thyroid hormone levels.1-3 Although typically called “subclinical hypothyroidism,” both large meta-analyses and treatment trials for isolated elevated TSH do not demonstrate harm associated with TSH<10 mIU/L or, benefit from treatment in this population.4,5 We have shown that isolated elevated TSH often reflects adaptations to aging rather than primary thyroid disease, implying that LT4 treatment could actually cause harm.6 This study aims to determine the effects of LT4 on survival among older adults

Conclusion: LT4 use in older adults is associated with a significantly increased mortality risk. This supports our hypothesis that isolated elevated TSH does not always represent subclinical hypothyroidism in older adults, and that treating TSH changes associated with aging adaptation could adversely alter key homeostatic compensations.

 

[madman]

Individuals taking class of steroid medications at high risk for COVID-19

Individuals taking a class of steroid hormones called glucocorticoids for conditions such as asthma, allergies and arthritis on a routine basis may be unable to mount a normal stress response and are at high risk if they are infected with the virus causing COVID-19, according to a new editorial published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Glucocorticoids are a class of medications used to treat a variety of inflammatory conditions and administered by many different routes, including tablets, topical creams and inhaled medications.Patients taking these medications may be more susceptible to COVID-19 as a result of the medication suppressing the immune system. They may also experience more severe disease once infected because these medications suppress their own steroid response to infection. Injectable supplemental glucocorticoid therapy in this setting can reverse the risk of potentially fatal adrenal failure and should be considered in every case.

Individuals with known primary adrenal insufficiency, also known as Addison’s disease, and secondary adrenal insufficiency occurring in hypopituitarism should also take extra precautions. If patients develop symptoms such as a dry continuous cough and fever, they should double their oral glucocorticoid dose immediately and continue doing so until the fever has subsided. They, too, will require injectable glucocorticoid therapy should their condition worsen.

Endocrinologists can play a key role in recognizing, managing and implementing these measures, according to the authors.

According to the World Health Organizations, there are more than 719,000 confirmed cases of COVID-19. More than 33,000 people have died from the disease as of March 31.

“In our professional lives, we have not witnessed a healthcare crisis of this magnitude and severity,” the authors wrote.

Among individuals with diabetes who contract COVID-19, the severity of the illness appears to be worse than in individuals who do not have diabetes, according to the authors. Published research from the Wuhan province in China found those with diabetes and high blood pressure were overrepresented among severely ill patients and those who died.

Scientists have already helped to uncover how the virus responsible for COVID-19 enters cells and spreads from one individual to another. Some have already made preliminary observations regarding the virus’ interactions with the endocrine system.

“Endocrine-related targets are at the forefront of discovery science as we collectively tackle this pandemic,” the authors wrote.

 

[madman]

Broken bone location can have significant impact on long-term health

In older individuals, the location of a broken bone can have significant impacts on long-term health outcomes, according to research accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

OR13-03: Understanding Why Older People with Low Trauma Fractures Die Prematurely Jacquelin

There is increasing evidence that all proximal and not just hip fractures are associated with increased mortality risk. However, the cause of this increased mortality is unknown. We sought to determine the post-fracture trajectories of subsequent hospital admissions and mortality to develop an understanding of why patients with non-hip fractures die prematurely.



This study has not only confirmed the increased mortality following proximal fractures but has demonstrated differing clinical trajectories between proximal and distal fractures that contribute to this increased mortality. These findings provide important insights as to why proximal fracture subjects die prematurely that may lead to specific avenues for intervention.

 

[madman]

Fracking chemical may interfere with male sex hormone receptor

A chemical used in hydraulic fracturing, commonly called fracking, has the potential to interfere with reproductive hormones in men, according to research accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

The study found the chemical can block the effects of testosterone and other male sex hormones known as androgens.

SAT-722: Structure-Based Discovery of Hydraulic Fracturing Chemicals as Novel Androgen Receptor Antagonists

Hydraulic fracturing (HF) technology is increasingly utilized for oil and gas extraction operations. The widespread use of HF has led to concerns of potential negative impacts on both the environment and human health. Indeed, the potential endocrine disrupting impacts of HF chemicals is one such knowledge gap. Herein, we used structure-based molecular docking to assess the binding affinities of 60 HF chemicals used in California to the human androgen receptor (AR). Five HF chemicals had relatively high AR binding affinity, suggesting the potential to disrupt AR effects. We next assessed androgenic and antiandrogenic activities of these chemicals in vitro. Of the five candidate AR ligands, only Genapol® X– 100 was found to significantly reduce the AR transactivation by 22%. To better understand the structural effect of Genapol® X–100 on the potency of receptor inhibition, we compared the antiandrogenic activity of Genapol® X–100 with that of its structurally similar chemical, Genapol® X–080. Interestingly, both Genapol® X–100 and Genapol® X–080 elicited a significant antagonistic effect with 20% relative inhibitory concentrations (RIC20) of 0.43 and 0.89 μM, respectively. This indicated that Genapol® X–100 was more potent in inhibiting AR than Genapol® X–080, consistent with longer Genapol® X–100 chain length causing greater potency of AR activity inhibition. Furthermore, we investigated the mechanism of AR inhibition of these two chemicals in vitro. The result revealed that both Genapol® X–100 and Genapol® X–080 inhibited AR through noncompetitive binding mechanism. The effects of these two chemicals on the expression of AR responsive genes such as PSA, KLK2, and AR were also investigated. Genapol® X–100 and Genapol® X–080 notably altered the expression of these genes at relatively low concentrations of 0.5 µM to 1 µM. Using these integrated in vitro and in silico approaches, we identified HF chemicals as novel noncompetitive AR antagonists. Our findings heighten awareness of endocrine disruption by HF chemicals and provide evidence that noncompetitive antiandrogenic Genapol® X–100 could possibly cause adverse endocrine health effects in humans.

 

[madman]

Androgen receptor stops tumor growth in the most common form of breast cancer

Researchers say they have found a viable new therapeutic strategy for estrogen receptor-positive (ER+) breast cancer, even cancers that are resistant to current standard of care treatments. Their new preclinical study was accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

OR05-06: The Androgen Receptor Is a Tumour Suppressor in Estrogen Receptor Positive Breast Cancer

There is strong interest in targeting the androgen receptor (AR) in estrogen receptor (ER) positive breast cancer, but widespread confusion exits as to what therapeutic strategy - agonism or antagonism - is appropriate. Current understanding of AR predominantly stems from the field of prostate cancer, where AR is the key oncogenic driver and therapeutic target. An ensuing assumption is that AR promotes malignancy in breast cancer and should be therapeutically antagonised. However, compelling preclinical data to support this assumption is lacking. Since estrogen stimulates and androgen inhibits the development of normal breast tissue, we hypothesized that AR acts as a tumour suppressor in the breast and that AR agonism is the appropriate therapeutic strategy for ER-driven breast cancer. We tested this hypothesis using a large suite of cell line and patient-derived explant (PDE) and xenograft (PDX) models of breast cancer, including those that were resistant to current therapies and those harbouring genomic anomalies of ESR1 associated with treatment-resistant disease. Across the diverse models we found compelling evidence that AR agonism, but not antagonism, potently and durably inhibited tumour growth. A signature of AR activity derived from the xenograft models positively predicted disease survival in multiple large clinical cohorts of ER+ breast cancer, out-performing other breast cancer-specific prognostic signatures. We also show that an AR agonist can be combined with current ER target therapies such as Tamoxifen or a CDK4/6 inhibitor to maximize growth inhibition. Mechanistically, agonist-bound AR opposed ER signalling by repositioning ER and the co-activator p300 in the chromatin landscape, resulting in down-regulation of cell cycle genes. Introduction of an AR DNA binding mutant had no effect on ER signalling or estrogen-stimulated growth in breast cancer cells. As part of this study, we have generated consensus AR cistromes representing ER+ breast cancer cell lines and ER+ tumours that provide a new understanding of AR activity and clearly show differences to those associated with prostate cancer cell lines and tumours. In conclusion, our data provides a compelling biological rationale for AR agonism as a therapeutic strategy in multiple, clinically relevant contexts of ER-positive breast cancer. These findings should dispel widespread confusion over the role of AR in ER driven breast cancer, an issue that currently hinders progress in leveraging modern AR-targeted therapies (e.g. selective androgen receptor modulators) that lack the undesirable side-effects of androgens for clinical benefit.

 

[madman]

Men with erectile dysfunction may face higher risk of death

Men with erectile dysfunction have a higher risk of death, regardless of their testosterone levels, suggests a study accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

"As both vascular disease and low testosterone levels can influence erectile function, sexual symptoms can be an early sign for increased cardiovascular risk and mortality," said lead researcher Leen Antonio, M.D., Ph.D., of KU Leuven-University Hospitals in Belgium.

OR02-06: Sexual Symptoms Predict All-Cause Mortality Independently of Sex Steroids in Ageing Men

Objective: To study the interrelationships between sex steroids, gonadotrophins and sexual symptoms with all-cause mortality in a large prospective cohort of European men.

Methods: 1913 community-dwelling men, aged 40-79, participated in the European Male Ageing Study (EMAS) between 2003-2005. Sexual symptoms were assessed via a validated questionnaire (EMAS-SFQ). Sex steroids were measured by mass spectrometry. In 5 of 8 EMAS centres, survival status was available until 1 April 2018. Cox proportional hazard models were used to study the association between hormones, sexual symptoms and mortality. Because of the wide age range at study entry, age was used as time-scale, instead of years since inclusion adjusting for age. Results were expressed as hazard ratios (HR) with 95% confidence intervals, adjusted for centre, BMI and smoking.

Results: 483 (25.3%) men died during a mean follow-up of 12.4±3.3 years. Men who died had a higher BMI (p=0.002), but smoking status did not differ. TT levels were similar in both groups, but FT was lower in those who died (mean±SD: 312±86 pmol/L vs 270±84, p<0.001) and LH was higher (5.7±3.3 U/L vs 7.8±5.8, p<0.001). Men in the lowest FT quartile had higher mortality risk compared to men in the highest quartile (HR 1.43 (1.06-1.95); p=0.021). Also men in the highest FSH quartile had increased mortality risk (HR 1.38 (1.02-1.88); p=0.036). However, there was no association with TT, E2 or LH. Men with 3 sexual symptoms had a higher mortality risk compared to men with no sexual symptoms (HR 1.77 (1.28-2.41); p<0.001). In particular erectile dysfunction and poor morning erections, but not lower libido, were associated with increased mortality (HR 1.40 (1.15-1.73); p=0.001; HR 1.30 (1.06-1.60); p=0.012; HR 1.14 (0.93-1.40); p=0.203 respectively). Further adjusting for TT and FT did not influence the observed HRs. Also in men with normal TT (>12 nmol/L), the presence of sexual symptoms increased mortality risk (HR 1.51 (1.15-1.97); p=0.003). Finally, men with TT<8 nmol/L and sexual symptoms had a higher mortality risk compared to men with normal TT and no sexual symptoms (HR 1.92 (1.05-3.52); p=0.035).

Conclusions: Men with the lowest FT and highest FSH levels have an increased mortality risk. Sexual symptoms, in particular erectile dysfunction, predict all-cause mortality independently of T levels. As both vascular disease and low T can influence erectile function, sexual symptoms can be an early sign for increased cardiovascular risk and mortality, as well as a sequela of low T.

 

[madman]

Liraglutide can help adolescents with obesity manage their weight

Liraglutide 3.0 mg, approved by the United States Food and Drug Administration (FDA) as an adjunct to a reduced-calorie diet and increased physical activity to help adults with obesity manage their weight, appears to help adolescents too, according to an industry-sponsored randomized controlled trial. The study was accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a supplemental issue of the Journal of the Endocrine Society.

OR33-01: Liraglutide for Weight Management in Pubertal Adolescents with Obesity: A Randomized Controlled Trial

Background: Pediatric obesity is a chronic disease with rising prevalence and limited treatment options; first-line intervention is lifestyle therapy, which is typically unsuccessful.1 Liraglutide (3.0 mg) as an adjunct to lifestyle therapy has provided weight loss and improved cardiometabolic risk factors in adults.2 Here we report the results of liraglutide 3.0 mg in adolescents with obesity who failed to respond to lifestyle therapy.

Methods: A multinational, randomized, double-blind trial (NCT02918279) with a 12-wk run-in of lifestyle therapy, 4-8-wk dose escalation, 52-wk maintenance period and 26-wk follow-up off trial drug. Adolescents aged 12-<18 years with obesity, stable weight and suboptimal response to lifestyle therapy alone were randomized 1:1 to once daily subcutaneous liraglutide 3.0 mg (or maximum tolerated dose) or placebo (PBO), both as an adjunct to lifestyle therapy. Randomization was stratified by pubertal and glycemic (normal vs prediabetes/type 2 diabetes) status. Primary endpoint was change in BMI standard deviation score (SDS)3 from wk 0 to 56.

Results: Of 125 adolescents randomized to liraglutide 3.0 mg and 126 to PBO, 101 and 100 completed treatment at wk 56, respectively; 99 in each arm completed the trial at wk 82. 40.6% were male; mean age 14.5 years; mean BMI 35.6 kg/m2; mean BMI SDS 3.17. Liraglutide 3.0 mg was superior to PBO for change in BMI SDS at wk 56 (estimated treatment difference [ETD] -0.22; 95% CI -0.37, -0.08; p=0.0022). In the liraglutide 3.0 mg vs PBO arm, 43.25% vs 18.73% (p=0.0002) and 26.08% vs 8.11% (p=0.0006) of adolescents had ≥5% and ≥10% reduction in baseline BMI at wk 56, respectively. A significant difference in change in BMI was seen for liraglutide 3.0 mg vs PBO: ETD -4.64%; 95% CI -7.14, -2.14; p=0.0003. A significant reduction in waist circumference with liraglutide 3.0 mg was shown at wk 56 (p=0.0126). Greater weight regain/rebound in BMI SDS at wk 82 was seen for liraglutide 3.0 mg vs PBO after drug discontinuation (ETD 0.15; 95% CI 0.07, 0.23; p=0.0002). There were no significant differences in blood pressure, fasting lipids, fasting plasma glucose or HbA1c at wk 56. No unexpected safety concerns and no severe hypoglycemia were reported. During treatment (0-56 wks), more adolescents in the liraglutide 3.0 mg (64.8%) vs PBO arm (36.5%) reported gastrointestinal adverse events (AEs), and 3 vs 5 adolescents, respectively, reported serious AEs. Mental health questionnaire results were similar in both arms at wk 56. No effect on growth or pubertal development was found.

Conclusions: This trial demonstrates clinically meaningful 4 weight loss in adolescents with obesity treated with liraglutide 3.0 mg as an adjunct to lifestyle therapy. The safety profile was similar to that observed in adults.

 

[madman]

Survey finds physicians struggle to communicate positive prognosis to thyroid cancer patients

Despite excellent prognosis with most thyroid cancers, many newly diagnosed patients have cancer-related worry, and physicians vary in their responses to patients' worry, according to new research accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.

“In this large population-based study, we found that physicians use different strategies to address this worry, with around half of them telling their patients that thyroid cancer is a ‘good cancer,’” said lead study author Maria Papaleontiou, M.D., an assistant professor of medicine in the Division of Metabolism, Endocrinology & Diabetes (MEND) at the University of Michigan in Ann Arbor, Mich. "Although treating physicians are likely trying to emphasize optimistic outcomes, no evidence currently exists to support the notion that telling patients they have a 'good cancer' is helpful.”

OR21-06: Physician Management of Thyroid Cancer Patients’ Worry: Is It “Good” Enough?

Introduction: Despite the excellent prognosis of most thyroid cancer patients, cancer-related worry is common. Additionally, patients report that being told by physicians that they have a “good cancer” invalidates their fears of having cancer and creates mixed and confusing emotions. However, it is not known what proportion of physicians try to reassure patients with the description “good cancer”.

Methods: Patients diagnosed with differentiated thyroid cancer in 2014-2015 from the Surveillance, Epidemiology and End Results Program (SEER) registries of Georgia and Los Angeles County were asked to identify endocrinologists and surgeons involved in managing their thyroid cancer. Physicians were surveyed using the modified Diliman method. They were asked to describe their thyroid cancer patients’ worry at time of diagnosis and what they tell them if worried. A multivariable logistic regression was conducted to identify physician characteristics associated with reporting thyroid cancer as a “good cancer”.

Results: Response rate was 69% (448/654). Overall, 40% were endocrinologists, 30% were general surgeons and 30% were otolaryngologists. A total of 8% of physicians reported that their patients are not worried or are a little worried at diagnosis, 27% that they are somewhat worried and 65% that they are quite or very worried. Ninety-one percent of physicians reported providing details on prognosis including information on death and recurrence to worried patients, 61% tell them their physicians are experienced in managing thyroid cancer, and 50% tell them that thyroid cancer is a “good cancer”. Factors associated with report of telling patients they have a “good cancer” included otolaryngology specialty [odds ratio (OR) 1.84, 95% confidence interval (CI) 1.07-3.17, compared to endocrinology), private practice setting (OR 2.57, 95% CI 1.42-4.75, compared to academic setting) and Los Angeles site (OR 2.23, 95% CI 1.46-3.45, compared to Georgia site). Physicians who perceived that their patients were quite or very worried at time of diagnosis were less likely to use this terminology (OR 0.55, 95% CI 0.35-0.84) and more likely to encourage patients to seek help outside of the physician-patient relationship (OR1.82, 95% CI 0.35-0.84), compared to patients not to somewhat worried.

Conclusion: Most physicians in our sample from two diverse geographic areas report perceiving patient worry as common at time of thyroid cancer diagnosis. They report addressing this worry with different strategies, including telling patients they have a “good cancer”. The benefit of such strategies on patient outcomes still needs further investigation.

 

[madman]

First FDA-approved drug for thyroid eye disease effective regardless of age, gender

Teprotumumab, the first FDA-approved medicine for thyroid eye disease, provides significant improvement in eye bulging, regardless of patient gender, age or smoking status, according to a study accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in a special supplemental section of the Journal of the Endocrine Society.


OR18-01: Effect of Teprotumumab on Proptosis Reduction Across Various Demographic Sub-Groups

Introduction: Teprotumumab, an insulin-like growth factor 1 receptor inhibitory monoclonal antibody, was recently shown to significantly reduce proptosis in patients with active, moderate-to-severe thyroid eye disease (TED) in phase 2 and phase 3 clinical trials.1,2 Prior analyses have demonstrated a combined trial proptosis response (≥2 mm reduction) rate of 77.4% in the teprotumumab group and 14.9% in the placebo group after 24 weeks of therapy (p < 0.001).3 The current analysis was performed to investigate whether or not patient demographic characteristics influence the teprotumumab proptosis response.

Methods: Data from two 24-week randomized, double-masked, placebo-controlled, parallel-group, multicenter studies (Phase 2 [NCT01868997], Phase 3 [NCT03298867[) were combined. All patients had active TED associated with Graves’ disease. The study eye designated at baseline manifested more severe TED and a clinical activity score of > 4. Subjects were divided into subgroups based on gender, smoking status, and age at baseline (younger: <65, older: ≥65). The percentage of proptosis (≥2 mm) responders and proptosis change from baseline were examined in each of these subgroups. Because most of both teprotumumab (85%) and placebo (87%) subjects were white, there were insufficient numbers of subjects to examine the effect of race on the teprotumumab proptosis response. All analyses were performed on the intent-to-treat (ITT) population using data from the study eye.

Results: A total of 171 patients comprised the population from the two studies. Eighty-four and 87 patients were randomized to the teprotumumab and placebo groups, respectively, and the treatment groups had balanced baseline characteristics. At week 24, significantly more teprotumumab than placebo patients were proptosis responders in all examined subgroups (male: 73.1% vs. 5.0%, female: 79.3% vs. 17.9%, smokers: 70.0% vs. 23.1%, non-smokers 79.7% vs. 11.5%, younger: 76.1% vs. 16.2%, older: 84.6% vs. 7.7%; all p < 0.001). In continuous variable analyses, the mean proptosis reduction from baseline was also significantly greater at week 24 in teprotumumab-treated patients than placebo patients (male: -3.34 vs. -0.07 mm, female: -3.10 vs. -0.42 mm, smokers: -2.99 vs. -0.72 mm, nonsmokers: -3.20 vs. -0.31 mm, younger: -3.10 vs. -0.39 mm, older: -3.55 vs. -0.22 mm; all p < 0.001).

Conclusion: Teprotumumab was effective across subgroups of age, gender, and smoking status in the pooled 24-week clinical trials.

 

[madman]

Cancer treatment with immune checkpoint inhibitors may lead to thyroid dysfunction

Thyroid dysfunction following cancer treatment with new treatments called immune checkpoint inhibitors is more common than previously thought, according to research that was accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

SAT-418: Finding the Needles in the Haystack: Harnessing the Electronic Health Record to Find Thyroid Immune Related Adverse Events

Background: Immune checkpoint inhibitors (CPIs) are being used to effectively treat a growing number of cancers but can cause immune related adverse events (irAE). Thyroid dysfunction is the most common endocrine irAE. A meta-analysis of clinical trials estimated that following CPI exposure, 6.6% will become hypothyroid and 2.9% will have hyperthyroidism 1. It is unclear if this reflects the real-world incidence of these irAEs. We used electronic health record (EHR) data to identify patients who developed thyroid dysfunction after CPI to estimate the real-world incidence of these irAEs.

Methods: Data were derived from the EHR of a large U.S. academic center. We identified subjects treated with CPIs between 2012 and 2018 and excluded those with thyroid cancer or pre-existing thyroid disease. Thyroid dysfunction was identified as either a TSH > 10, an abnormal free T4 or a prescription for thyroid hormone replacement or anti-thyroid medication. Those with thyroid dysfunction were then categorized as having pre-existing disease or a new-onset thyroid irAE based on the timing of CPI initiation. Logistic regression was used to evaluate the association of thyroid irAE with age, gender, CPI and type of cancer.

Results: In total, 1146 individuals without pre-existing thyroid disease that received CPIs were assessed. Pembrolizumab was the most common treatment (45%), followed by nivolumab (20%). Less than 10% of subjects received atezolizumab, durvalumab, ipilimumab monotherapy, combined ipilimumab/nivolumab, or other combinations of CPIs. Melanoma was the most common cancer treated (32%), followed by non-small cell lung cancer (13%). The prevalence of any other cancer was < 10% each. Overall, 19% developed thyroid irAEs. After adjustment for gender and age, the type of cancer was significantly associated with new onset thyroid dysfunction (p=0.01). The rates of thyroid irAEs ranged from 10% in glioblastoma to 40% in renal cell cancer. Although there was no significant association between irAEs and specific CPIs in the overall analysis, thyroid irAEs were more common in subjects who received combined ipilimumab/ nivolumab (31%) compared to pembrolizumab (18%, p=0.03), nivolumab (18%, p<0.01) and ipilimumab (15%, p=0.02).

Conclusion: Thyroid irAEs are much more common in real world practice than in clinical trials and there is emerging evidence that certain cancer types incur a higher risk of thyroid irAEs even after adjustment for CPI exposure. Clinicians and patients should be educated about these risks. Future work should focus on exploring the reasons underlying the differing rates of thyroid irAEs among different cancers including effect on cancer outcomes.

 

[madman]

Poor fitness may impede long-term success in weight loss program

People who are very out of shape when they begin a behavioral weight loss program lose less weight in the long term than those who are more fit, suggests a new study that was accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

SAT-575: Association Between Baseline Fitness and Changes in Physical Activity and Weight Loss in an 18-Month Behavioral Weight Loss Program

Purpose: To determine the association between baseline fitness and changes in body weight and device measured levels of moderate-to-vigorous physical activity (MVPA) during a BWLP.

Methods: Adults (n=85) were enrolled in an 18-month BWLP combining a calorie-restricted diet, group based behavioral support, and 6 months of supervised exercise (progressing to 300 min/wk of moderate-intensity) followed by 12 months of unsupervised exercise. Data from 60 completers (age 41.0±9.5 years, BMI 34.6±4.2 kg/m2, 80% female) were used in this analysis. MVPA was measured over 1 week with the Sensewear Armband at months 0, 6, 12, and 18. Fitness (VO2max) was measured on a treadmill using indirect calorimetry and categorized based on published age and sex norms (Physical Fitness Specialist Certification Manual, 1997). A linear mixed effects model with unstructured covariance was used to examine the association between baseline fitness category and changes in body weight, total MVPA, and MVPA in bouts ≥10 min at the four time points.

Results: Of the 60 completers, 33% (n=20) were classified as having very poor fitness, 45% (n=27) poor, 18% (n=11) fair, 3% (n=2) good, and 0% (n=0) excellent or superior. Due to the low proportion of participants categorized as having fair or better fitness, we created a binary fitness variable (very poor vs. poor or better). Baseline BMI was higher in those in the very poor category compared to those in the poor or better category (36.2±4.2 vs 33.7±4.0, p=0.03). There were no significant differences between the two fitness categories in weight change at 6 or 12 months. However, at 18 months, mean weight loss was 4.3±1.7 kg in those in the very poor category and 8.2±1.2 kg in those in the poor or better category, with a marginally significant between-group difference (p=0.07). There were no differences in changes in total or bout MVPA. However, those with very poor fitness had lower bout MVPA at baseline vs. those with poor or better fitness (16±20 vs 33±31 min/d, p=0.03). At 18 months, both groups increased bout MVPA, however bout MVPA remained lower in the very poor vs. poor or better group (24±29 vs 42±29 min/d, p=0.03). Total MVPA showed a similar pattern.

Conclusion: Baseline fitness may moderate 18-month weight loss, as those with very poor fitness lost less weight compared to those with poor or better fitness levels. Those with poor or better fitness at baseline achieved significantly higher mean levels of MVPA at 18 months compared to those with very poor fitness. Participants with very poor fitness at baseline may require additional exercise support during a BWLP to achieve the high levels of MVPA recommended for weight loss maintenance.

 

[madman]

Unconscious food cravings may make bariatric surgery less effective for people with extreme obesity

Patients with extreme obesity are prone to unconscious food impulses and cravings that may make it challenging for them to maintain weight loss after bariatric surgery, according to research that was accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

The most effective treatment for severe obesity is bariatric, or weight loss, surgery. People whose body mass index is above 50 kg/m2 meet the criteria for super obesity. Individuals with super obesity seem to be more prone to regain weight following a period of apparent success after bariatric surgery, according to lead researcher Rogerio Friedman, M.D., Ph.D. of Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil. “The proportion of patients who regain weight after a variable time following bariatric surgery can be as high as 20%,” he said.

Friedman and colleagues wanted to find out whether behavioral and cognitive factors before and after bariatric surgery might explain the differences in weight regain. “The intake of food is regulated by brain centers that control appetite and satiety,” he said. “Part of our intake is the result of automatic responses, and part comes from conscious, deliberate choices.”

The researchers focused on attentional bias, the tendency to pay attention to some things while simultaneously ignoring others. Previous research has found that attentional bias is associated with binge eating and emotional eating, and it can contribute to obesity. “Attentional bias also happens in smokers, and people who abuse drugs and alcohol,” Friedman said.

The study included 59 people four years after they had received Roux-en-Y gastric bypass surgery. Half of them had super obesity. The researchers measured attentional bias through a computerized task, where individuals had to indicate the direction of an arrow that appeared immediately after selected images were shown. If a person had a greater number of correct responses for food images, they were determined to have an attentional bias for visual food clues.

The study measured two types of attentional bias: pre-conscious and conscious. “The pre-conscious part or our attention is that millisecond when our eyes are caught by something before we even realize it. It’s is highly automatic,” Friedman said. Conscious attentional bias lasts long enough for a person to become aware of it. “You realize the image is there, and you have time to think about it—you can make a choice,” he said.

The study flashed images for 2 seconds to measure conscious attentional bias, and a half second and one-tenth of a second to measure preconscious attentional bias. All patients maintained a conscious attentional bias for food (meaning that they knew the image was catching their attention), but only the patients with super obesity also had a preconscious attentional bias—the image caught their attention before they even realized it. “This may be a predisposing factor to weight regain,” Friedman said.

“The findings suggest that the same cognitive processes that operate in addiction are present in morbid obesity as well,” he said. “Cognitive and behavioral phenomena are behind many aspects of obesity; they remain present after bariatric surgery and may at least in part explain the failure of different treatments. As long as our treatment approach keeps failing to address such phenomena, we may be far from successfully controlling the disease.”

 

[madman]

Coconut oil reduces features of metabolic syndrome in obese females, animal study finds

Obese females that ate a small amount of coconut oil daily, even as part of a high-fat diet, had decreased features of metabolic syndrome, a cluster of risk factors that raise the chances of developing diabetes, heart disease and stroke, an animal study finds. The study results were accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

“Our controlled experimental study suggests that coconut oil may not be bad for cardiometabolic health, contrary to what previous studies have concluded,” said the study’s lead investigator, Annie Newell-Fugate, D.V.M., Ph.D., an assistant professor at Texas A&M University in College Station, Texas.

SUN-663: Dietary Coconut Oil Mitigates Features of Metabolic Syndrome in Obese Females

These data demonstrate that small amounts of dietary coconut oil, even as a part of a high fat diet, can mitigate features of metabolic syndrome and decrease hepatic and visceral adipose tissue lipid accumulation in obese females.

 

[madman]

Most internists-in-training feel ill-equipped to treat obesity

Most resident physicians training in internal medicine do not feel adequately prepared to manage obesity in their patients, a new survey from a California residency program finds. The results were accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

"We are not training our next generation of doctors to feel comfortable with or knowledgeable about management of obesity, a disease rapidly increasing in prevalence that underlies many other medical conditions," said lead researcher Mita Shah Hoppenfeld, M.D. Hoppenfeld is a fourth-year internal medicine resident at Stanford University in Palo Alto, Calif., where she conducted the survey.

MON-LB105: Resident Obesity Management: Comfort Correlates with Action

Most residents surveyed do not feel adequately prepared to provide evidence-based management of obesity via lifestyle changes counseling, WMM prescription, or specialty care referral. Comfort and knowledge of system processes/resources and WMMs are critical to resident management of obesity. These are potential targets for educational intervention in residency curricula that may improve care for patients with obesity.

 

[madman]

Technology use by adults with type 1 diabetes lower among African Americans, Hispanics

Continuous glucose monitor (CGM) and continuous subcutaneous insulin infusion (CSII) devices are known to improve outcomes in patients with type 1 diabetes (T1D), yet African American and Hispanic patients face barriers to the use of these devices, according to results of a small single-center retrospective study. The results of the ENDO 2020 abstract will be published in the Journal of the Endocrine Society.

“We observed that the use of technology among Caucasians was higher than its use in other racial and ethnic groups, and the difference was statistically significant,” said lead author Kamonkiat Wirunsawanya, M.D., an endocrinology fellow at Boston University Medical Center in Boston, Mass. "Our study included an adult population that is more racially diverse than seen in the currently available literature."

OR30-03: Racial Differences in Technology Use Among Type 1 Diabetes in a Safety-Net Hospital

Objective: There is limited data regarding the use of diabetes technology such as continuous glucose monitor (CGM) and continuous subcutaneous insulin infusion (CSII) among patients with type 1 diabetes (T1D) in a minority serving and safety-net hospital. We examined racial differences in the use of CGM and CSII in this setting.

Methods: A retrospective review of 227 patients ≥ 18 years of age with T1D seen in the Endocrinology clinic at a safety-net hospital from October 2016 and September 2017 was completed. Statistical analysis assessed the likelihood of diabetes technology use among different races.

Results: The mean age was 39, 59% male, mean duration of diabetes was 21 years, 30% overweight, 22% obesity, 80% English speaking, and 50% had government insurance. In terms of the distribution of race/ethnicity, 43% were Caucasian, 25% African American (AA), 15% Hispanic, 15% defined as other, and 2% Asian. Mean HbA1c ± standard deviation (SD) of any technology (either CGM or CSII or both) and non-technology users were 8.27 ± 1.58 and 9.49 ± 2.04, respectively. Patients who had government health insurance were found to have lower odds of using technology (odds ratio [OR], 0.43; 95% confidential interval [CI], 0.25 - 0.74) compared to patients who had private health insurance. Overall, 26% of the patients used CSII with 43% of this population Caucasian, 10.5% AA and 14.2% Hispanic. The overall CGM use was 30% with 47% of users Caucasian, 14% AA and 22% Hispanic. In a multivariable logistic regression model that adjusted for insurance and language, AA or other were found to have statistically significant lower odds of using technology (AA OR 0.25 [95% CI 0.11 - 0.53] and other OR 0.33 [95% CI 0.12 - 0.89]) compared to the Caucasian group.

Conclusion: Our study showed that the use of technology in the Caucasian group was statistically significantly higher than in the non-Caucasian groups except for the Asian group. After adjusting for insurance and language, AA and other demonstrated statistically lower rates of technology use. Racial differences in diabetes technology use were observed in our study as well as the association between technology use and lowered HbA1c. Given diabetes technology is a useful tool in reducing HbA1c and hypoglycemia, the barriers to accessing diabetes technology in non-Caucasian individuals should be addressed to decrease health disparities.

 

[madman]

Wearable delivery device allows patients with type 2 diabetes to safely use more affordable insulin option

Adults with type 2 diabetes requiring insulin therapy can safely achieve good blood sugar control using regular human insulin (RHI) in a wearable, patch-like insulin delivery device called V-Go®, a new study finds. Results of the randomized controlled study—which was accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society—suggest “a more affordable option” for insulin therapy than newer insulin types, the researchers said.

“The modern insulins—rapid acting insulin (RAI) analogs—have dominated the mealtime insulin market for years, but skyrocketing prices have resulted in concerns of affordability and whether their differences from other available insulins are clinically relevant,” said study lead investigator Pablo Mora, M.D., an endocrinologist at Dallas Diabetes Research Center at Medical City, Dallas, Texas.

OR30-02: Efficacy and Safety Comparison Between U100 Regular Human Insulin and U100 Rapid Acting Insulin When Delivered by a 24 Hour Wearable Insulin Delivery Device in Type 2 Diabetes


Introduction: Increasing insulin prices have led to a renewed debate to determine if Rapid Acting Insulin (RAI) analogs offer an advantage over less expensive Regular Human Insulins (RHI). The steep increase in the cost of RAI has led to rationing of insulin or the total discontinuance of therapy by many patients due to cost. For many, RHI provides a more affordable option for insulin therapy when compared to RAI, especially if the limitations of the insulin profile can be overcome by delivering RHI through continuous subcutaneous insulin infusion (CSII) using a wearable insulin delivery device. To our knowledge, no data exists in a type 2 diabetes (T2D) population comparing RAI to RHI when delivered via CSII.

Methods: This 14 week multi-center prospective, randomized parallel, non-inferiority study in a T2D population compared the efficacy and safety of RAI versus RHI when delivered by V-Go®, a 24-hr wearable patch-like insulin delivery device that provides a preset continuous basal rate of insulin and on-demand bolus dosing. This study was conducted in a real-world practice setting under usual standard of care. Glucose lowering agents were to remain stable unless removal warranted due to documented clinically significant hypoglycemia and the only specific guidance for insulin titration was to down-titrate if blood glucose levels were consistently lower than target range. Patients administering RAI with V-Go were randomized 1:1 to continue RAI or to switch to RHI. Primary endpoint assessed non-inferiority for the between group net difference in HbA1c derived from a mixed model analysis. Between group differences from baseline for insulin total daily dose (TDD) and hypoglycemia (based on 7 point glucose profiles) were evaluated as secondary endpoints.

Results: One hundred thirteen patients (59 RHI and 54 RAI) were evaluated. Baseline characteristics were similar between cohorts. The mean change in HbA1c with RHI was -0.60% from a baseline of 8.41% vs -0.38% from a baseline of 8.33% with RAI (estimated treatment difference [ETD]: -0.22%; 95% confidence interval [CI] -0.67% to 0.22%; non-inferiority margin<0.4% and p=0.007). The mean change in TDD with RHI was 0.8 U/day from a baseline of 61.0 U/day vs 1.8 U/day from a baseline of 61.3 U/day with RAI (ETD: -1.04 U/day; 95% CI: -3.18 U/day to 1.11 U/day; p=0.92). The absolute change in percent of patients reporting hypoglycemia (≤ 70 mg/dL) from pre-randomization to post-randomization was +5.08% with RHI vs + 5.56% with RAI (ETD: -0.48%; 95% CI: -10.6% to 9.1%; p=0.91). Severe hypoglycemia was not reported in either cohort.

Conclusion: Patients with T2D administering RAI with V-Go can safely switch to RHI maintaining similar glycemic control.

 

[madman]

Artificial intelligence could help predict future diabetes cases

A type of artificial intelligence called machine learning can help predict which patients will develop diabetes, according to an ENDO 2020 abstract that will be published in a special supplemental section of the Journal of the Endocrine Society.

SAT-LB121: Development of a Machine-Learning Method for Predicting New Onset of Diabetes Mellitus: A Retrospective Analysis of 509,153 Annual Specific Health Checkup Records

In conclusion, the machine learning-based prediction model satisfactorily identified the DM onset prior to the actual incidence.

 

[madman]

Consuming extra calories can help exercising women avoid menstrual disorders

Exercising women who struggle to consume enough calories and have menstrual disorders can simply increase their food intake to recover their menstrual cycle, according to a study accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in the Journal of the Endocrine Society.

OR31-07: Increased Caloric Intake Improves Regularity of Menses and Is Associated with Increased TT3 and Leptin in Exercising Women with Oligo/amenorrhea: The "REFUEL" Randomized Controlled Trial

Overall, a nutritional intervention designed to increase energy intake by a moderate amount in exercising women with oligo/amenorrhea successfully improved body mass and fat mass, concentrations of metabolic hormones, and the likelihood of experiencing menses compared to oligo/amenorrheic women who maintained exercise and eating habits. As such, treatment plans designed to increase energy intake can be successful in reversing energetic suppression and recovering menses.

 

[madman]

Bariatric surgery may be effective treatment for non-alcoholic fatty liver disease

Bariatric surgery may be an effective treatment for non-alcoholic fatty liver disease (NAFLD), suggests a new study accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and publication in the Journal of the Endocrine Society.

The study compared three types of bariatric, or weight loss, surgery: gastric sleeve, gastric band and gastric bypass. “We believe that gastric bypass may be the best surgical option in these patients,” said lead researcher Marta Borges-Canha, Ph.D., of Centro Hospitalar Universitário de São João in Porto, Portugal.

MON-592: The Impact of Bariatric Surgery on the Risk of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients

Introduction: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, and the prevalence of both diseases is increasing notably. The lack of effective treatment options for NAFLD is leading to a great consideration towards the identification of new approaches.

Aim: We aimed to evaluate the change one year after bariatric surgery of parameters of hepatic function and in the hepatic scores, Fatty Liver Index (FLI, predictor of hepatic steatosis), and BARD, BMI, AST/ALT ratio and DM, (predictor of hepatic fibrosis).

Methods: Observational retrospective cohort study in morbidly obese patients that underwent bariatric surgery between January 2010 and July 2018. We excluded patients missing hepatic function parameters before or one year after the surgical procedure. We used two linear regression models: 1) unadjusted; 2) adjusted for surgery type (gastric sleeve, gastric band and gastric bypass), sex, age, body mass index, diabetes and dyslipidaemia.

Results: The included population (n=1955) had an average age of 43.1±10 years and 85.8% were female. We observed a relevant decrease in transaminases (pre-operative AST and ALT, 24.8±12.4 and 29.5±19.5U/L, vs 22.4 ± 11.1 and 22.2±14.7 post-operatively, respectively, p<0.01) and gamma glutamyltransferase (36.9±35.4 vs 21.4±22.0U/L, p<0.01), and an increase in alkaline phosphatase (77.8±23.5 vs 80.8±25.4U/L, p<0.01) and total bilirubin (0.56±0.23 vs 0.68±0.24mg/dL, p<0.01). Both FLI and BARD markedly decrease one year after surgery (p<0.01). Comparing the surgical procedures, gastric sleeve was associated with a greater reduction of hepatic enzymes and of both FLI and BARD comparing with gastric band. Comparing with gastric bypass, sleeve was associated with a greater reduction of transaminases and alkaline phosphatase, but a smaller reduction of FLI and BARD.

Conclusion: Bariatric surgery is associated with a reduction of the hepatic enzymes and an improvement of FLI and BARD. Bariatric surgery may represent an effective therapeutic approach to NAFLD.

 

[madman]

Researchers offer hope for an oral, non-injectable treatment of acromegaly

Adults who need medical maintenance treatment of the growth hormone disorder acromegaly respond well to an investigational oral form of the drug octreotide, investigators of the Chiasma OPTIMAL study reported. Results of the phase 3 randomized controlled clinical trial were accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in the Journal of the Endocrine Society.

OR23-07: Results from the Phase 3, Randomized, Double-Blind, Placebo-Controlled CHIASMA OPTIMAL Study of Oral Octreotide Capsules in Adult Patients with Acromegaly

Octreotide capsules were safe and well tolerated; no new/unexpected safety signals were observed. Most patients (55/56) experienced at least one treatment emergent adverse event; most were mild or moderate in intensity.

Overall, 90% of patients who completed the trial on octreotide capsules opted to enter the open label extension phase. These phase 3 data demonstrate octreotide capsules to be potentially safe and effective for the treatment of adults with acromegaly.