ß Cell function after Roux-en-Y gastric bypass surgery or reduced energy intake alone in people with obesity.

BackgroundThe effects of diet-induced weight loss (WL) and WL after Roux-en-Y gastric bypass (RYGB) surgery on ß cell function (BCF) are unclear because of conflicting results from different studies, presumably because of differences in the methods used to measure BCF, the amount of WL between treatment groups, and baseline BCF. We evaluated the effect of WL after RYGB surgery or reduced energy intake alone on BCF in people with obesity with and without type 2 diabetes.MethodsBCF (insulin secretion in relationship to plasma glucose) was assessed before and after glucose or mixed-meal ingestion before and after (a) progressive amounts (6%, 11%, 16%) of WL induced by a low-calorie diet (LCD) in people with obesity without diabetes, (b) ~20% WL after RYGB surgery or laparoscopic adjustable gastric banding (LAGB) in people with obesity without diabetes, and (c) ~20% WL after RYGB surgery or LCD alone in people with obesity and diabetes.ResultsDiet-induced progressive WL in people without diabetes progressively decreased BCF. Marked WL after LAGB or RYGB in people without diabetes did not alter BCF. Marked WL after LCD or RYGB in people with diabetes markedly increased BCF, without a difference between groups.ConclusionMarked WL increases BCF in people with obesity and diabetes but not in people with obesity without diabetes. The effect of RYGB-induced WL on BCF is not different from the effect of matched WL after LAGB or LCD alone.trial registrationNCT00981500, NCT02207777, NCT01299519.FundingNIH grants R01 DK037948, P30 DK056341, P30 DK020579, UL1 TR002345.

Association of pancreatitis with risk of diabetes: analysis of real-world data.

Introduction: Diabetes is a major cause of disease burden with considerable public health significance. While the pancreas plays a significant role in glucose homeostasis, the association between pancreatitis and new onset diabetes is not well understood. The purpose of this study was to examine that association using large real-world data. Materials and methods: Utilizing the IBM® MarketScan® commercial claims database from 2016 to 2019, pancreatitis and diabetes regardless of diagnostic category, were identified using International Classification of Diseases, Tenth Revision [ICD-10] codes. We then performed descriptive analyses characterizing non-pancreatitis (NP), acute pancreatitis (AP), and chronic pancreatitis (CP) cohort subjects. Stratified Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of diabetes across the three clinical categories. Results: In total, 310,962 individuals were included in the analysis. During 503,274 person-years of follow-up, we identified 15,951 incident diabetes cases. While men and women had higher incidence rates of CP and AP-related diabetes, the rates were significantly greater in men and highest among individuals with CP (91.6 per 1000 persons-years (PY)) followed by AP (75.9 per 1000-PY) as compared to those with NP (27.8 per 1000-PY). After adjustment for diabetes risk factors, relative to the NP group, the HR for future diabetes was 2.59 (95% CI: 2.45-2.74) (P<0.001) for the CP group, and 2.39 (95% CI: 2.30-2.48) (P<0.001) for the AP group. Conclusion: Pancreatitis was associated with a high risk of diabetes independent of demographic, lifestyle, and comorbid conditions.

Association of Adiposity With Incident Diabetes Among Black Adults in the Jackson Heart Study.

Background The prognostic value of anthropometric, adipokine, and computed tomography measures of adiposity to predict diabetes in Black, specifically by normoglycemia versus prediabetes, remains incompletely understood. Methods and Results Among Black participants without diabetes in the JHS (Jackson Heart Study), waist circumference [WC], body mass index, adiponectin, leptin, and leptin:adiponectin ratio were standardized in sample 1 (2422 participants at baseline [2000-2004]) and WC, body mass index, visceral adipose tissue (VAT), subcutaneous adipose tissue, and liver attenuation in 1537 participants at examination 2 (2005-2008) (sample 2). Hazard ratios (HRs) for diabetes were estimated using interval-censored Cox modeling adjusting for traditional risk factors and validated with the C index. Over 5 years, 300 and 122 incident diabetes cases occurred in sample 1 and sample 2, respectively. In sample 1 and sample 2, a 1-SD higher log-leptin:adiponectin ratio and VAT had the strongest associations (HR, 1.95 [95% CI, 1.67-2.27] and 1.76 [95% CI, 1.52-2.04]) and discriminatory power (C index 0.68 [95% CI, 0.64-0.71] and C index 0.67 [95% CI, 0.61-0.74]) with diabetes. The normoglycemic compared with the prediabetes group had a 1.3 to 1.9 times greater magnitude of associations with diabetes for WC, liver attenuation, and VAT (P interaction <0.10). In sample 2, C indices for WC (HR, 0.84; 95% CI, 0.73-0.95), VAT (HR, 0.91; 95% CI, 0.85-0.98), and liver attenuation (HR, 0.90; 95% CI, 0.77-1.00) were greater than HbA1c (HR, 0.74; 95% CI, 0.57-0.90) in normoglycemia, whereas HbA1c was best in prediabetes (HR, 0.72; 95% CI, 0.66-0.78). Conclusions Overall, among Black adults, multiple measures of adiposity were associated with incident diabetes with modest predictive ability. In Black patients with normoglycemia, WC, liver attenuation, and VAT may appropriately identify those at high risk for diabetes, whereas HbA1c was the best predictor in individuals with prediabetes.

Identification of a Risk Profile for New-Onset Diabetes After Acute Pancreatitis.

OBJECTIVES: There is a paucity of studies evaluating predictors of new-onset diabetes mellitus (DM) after acute pancreatitis (AP-related DM). We used a population-based database to evaluate predictors of AP-related DM. METHODS: The Nationwide Readmissions Database (2010-2014) was used to identify all nondiabetic adults with an index primary diagnosis of AP. Multiple exclusions were applied to identify cohorts with and without AP-related DM. A case-control study was conducted to identify risk factors for developing AP-related DM within the calendar year. RESULTS: We identified 2510 subjects with AP-related DM and 40,308 controls with AP who did not develop DM. Multivariable analysis revealed that increasing age (50-64 years; adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.14-1.60), male sex (aOR, 1.2; 95% CI, 1.03-1.40), lowest income quartile (aOR, 1.48; 95% CI, 1.18-1.84), Elixhauser comorbidity index of 3 or higher (aOR, 1.47; 95% CI, 1.23-1.75), components of metabolic syndrome (aOR, 2.12; 95% CI, 1.21-3.70), severe AP (aOR, 1.60; 95% CI, 1.34-1.90), and recurrent AP (aOR, 1.46; 95% CI, 1.24-1.72) were independently associated with increased risk of AP-related DM. CONCLUSIONS: These population-level variables predictive of developing AP-related DM can potentially identify patients who may benefit from closer follow-up, intensive education, and implementation of preventative strategies.

Needs Assessment for Weight Management: The Learning Health System Network Experience.

OBJECTIVE: To assess patients' weight management needs and experiences across multiple sites within the Learning Health System Network. PATIENTS AND METHODS: A total of 19,964 surveys were sent to patients identified with overweight or obesity through medical record query at 5 health care systems throughout 11 states. The survey collected patients' experiences with and opinions about weight management in clinical care from October 27, 2017, through March 1, 2018. RESULTS: Among the 2380 responders, being younger, female, nonwhite, and single and having some college education or less were all significantly associated with higher body mass index (BMI). The most frequent weight loss barriers included food cravings (30.7%-49.9%) and having a medical condition limiting physical activity (17.7%-47.1%) (P<.001). Higher BMI was associated with a higher frequency of comorbidities and lower health status (P<.001). Higher BMI was also associated with a higher belief that primary care providers (PCPs) should be involved in weight loss management (P=.01) but lower belief that the PCP had the necessary skills and knowledge to help (P<.001). Responders with a higher BMI were more likely to feel judged (P<.001) and not always respected (P<.001) by their PCP. In addition, those with a higher BMI more frequently reported avoiding health care visits because of weight gain, not wanting to undress or be weighed, and not wanting to discuss their weight with their PCP (P<.001). CONCLUSION: Physician involvement in weight management is important to patients whose needs and experiences differ by BMI. These data may inform clinical weight management efforts and create greater alignment with patient expectations.

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle.

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo and noninvasively in humans via phosphorus-31 magnetic resonance spectroscopy (31PMRS). However, the approach has not been widely adopted in translational and clinical research, with variations in methodology and limited guidance from the literature. Increased optimization, standardization, and dissemination of methods for in vivo 31PMRS would facilitate the development of targeted therapies to improve OXPHOS capacity and could ultimately favorably impact cardiovascular health. 31PMRS produces a noninvasive, in vivo measure of OXPHOS capacity in human skeletal muscle, as opposed to alternative measures obtained from explanted and potentially altered mitochondria via muscle biopsy. It relies upon only modest additional instrumentation beyond what is already in place on magnetic resonance scanners available for clinical and translational research at most institutions. In this work, we outline a method to measure in vivo skeletal muscle OXPHOS. The technique is demonstrated using a 1.5 Tesla whole-body MR scanner equipped with the suitable hardware and software for 31PMRS, and we explain a simple and robust protocol for in-magnet resistive exercise to rapidly fatigue the quadriceps muscle. Reproducibility and feasibility are demonstrated in volunteers as well as subjects over a wide range of functional capacities.

Alterations in energy balance following exenatide administration.

Exenatide is a medication similar in structure and effect to native glucagon-like peptide-1, an incretin hormone with glucose-lowering properties. The aim of the study was to measure the change in total energy expenditure (TEE) and body composition during exenatide administration and by deduction the relative contributions of energy expenditure and energy intake to exenatide-induced weight loss. Forty-five obese (body mass index, 30-40 kg·m⁻²) subjects were identified. After exclusion criteria application, 28 subjects entered into the study and 18 subjects (12 female, 6 male) completed the study, which consisted of 6 visits over 14 weeks and injection of exenatide for an average of 84 ± 5 days. Respiratory gas analysis and doubly labeled water measurements were performed before initiation of exenatide and after approximately 3 months of exenatide administration. The average weight loss from the beginning of injection period to the end of the study in completed subjects was 2.0 ± 2.8 kg (p = 0.01). Fat mass declined by 1.3 ± 1.8 kg (p = 0.01) while the fat-free mass trended downward but was not significant (0.8 ± 2.2 kg, p = 0.14). There was no change in weight-adjusted TEE (p = 0.20), resting metabolic rate (p = 0.51), or physical activity energy expenditure (p = 0.38) and no change in the unadjusted thermic effect of a meal (p = 0.37). The significant weight loss because of exenatide administration was thus the result of decreasing energy intake. In obese nondiabetic subjects, exenatide administration did not increase TEE and by deduction the significant weight loss and loss of fat mass was due to decreased energy intake.

Effect of smoking status on total energy expenditure.

Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean ± SD) between smokers and never smokers for either males (27.8+5.1 kg/m2 vs. 27.5+4.0 kg/m2) or females (26.5+5.3 kg/m2 vs. 28.1+6.6 kg/m2), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status.

Exenatide and weight loss.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone mainly released from the distal ileum, jejunum, and colon in response to food ingestion. It is categorized as an incretin due to its activation of GLP-1 receptors in pancreatic beta-cells leading to insulin exocytosis in a glucose-dependent manner. Exenatide (synthetic exendin-4) is a subcutaneously injected GLP-1 receptor agonist that shares 50% homology with GLP-1. It is derived from lizard venom and stimulates the GLP-1 receptor for prolonged periods. The present review aims to enumerate exenatide-instigated weight loss, summarize the known mechanisms of exenatide-induced weight loss, and elaborate on its possible application in the pharmacotherapy of obesity. METHODS: A search through PubMed was performed using exenatide and weight loss as search terms. A second search was performed using exenatide and mechanisms or actions as search terms. RESULTS: In addition to exenatide's action to increase insulin secretion in individuals with elevated levels of plasma glucose, clinical trials have reported consistent weight loss associated with exenatide treatment. Studies have found evidence that exenatide decreases energy intake and increases energy expenditure, but findings on which predominates to cause weight loss are often inconsistent and controversial. CONCLUSION: Further research on the effects of exenatide treatment on energy intake and expenditure are recommended to better understand the mechanisms through which exenatide causes weight loss.