Glucagon-like peptide-1 effect on ß-cell function varies according to diabetes remission status after Roux-en-Y gastric bypass.

AIMS: The contribution of endogenous glucagon-like peptide (GLP)-1 to ß-cell function after Roux-en-Y gastric bypass surgery (RYGB) is well established in normoglycaemic individuals, but not in those with postoperative hyperglycaemia. We, therefore, studied the effect of GLP-1 on ß-cell function in individuals with varying degrees of type 2 diabetes mellitus (T2D) control after RYGB. MATERIALS AND METHODS: Glucose, insulin secretion rates, ß-cell glucose sensitivity and glucagon were measured during an oral glucose tolerance test before (saline only) and at 3, 12 and 24 months after RYGB with and without infusion of the GLP-1 receptor blocker exendin9-39 (EX9). The cohort was retrospectively classified based on T2D remission (REM) status at the latest study time point: REM (n = 5), persistent T2D (n = 8), or impaired glucose tolerance (n = 16). RESULTS: EX9 blunted the increase in ß-cell glucose sensitivity at 3 months (-44.1%, p < .001) and 12 months (-43.3%, p < .001), but not at 24 months (-12.4%, p = .243). EX9 enhanced postprandial glucagon concentrations by 62.0% at 3 months (p = .008), 46.5% at 12 months (p = .055), and 30.4% at 24 months (p = .017). EX9 counterintuitively decreased glucose concentrations at 3 months in the entire cohort (p < .001) but had no effect on glycaemia at 12 and 24 months in persistent T2D and impaired glucose tolerance; it minimally worsened glycaemia in REM at 12 months. CONCLUSIONS: GLP-1 blockade reversed the improvement in ß-cell function observed after RYGB, but this effect varied temporally and by REM status. GLP-1 blockade transiently and minimally worsened glycaemia only in REM, and lowered postprandial glucose values at 3 months, regardless of REM status.

Role of the Gut in the Temporal Changes of ß-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission.

OBJECTIVE: The role of the gut in diabetes remission after Roux-en-Y gastric bypass (RYGB) is incompletely understood. We assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Longitudinal, prospective measures of ß-cell function were assessed after oral glucose intake and graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n = 29), 12 (n = 24), and 24 (n = 20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. RESULTS: The decreases in body weight, fat mass, waist circumference, and insulin resistance after surgery (all P < 0.001 at 12 and 24 months) did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in ß-cell glucose sensitivity after oral glucose intake differed by remission status (P = 0.04): greater (6.5-fold; P < 0.01) and sustained in those in full remission, moderate and not sustained past 12 months in those with partial remission (3.3-fold; P < 0.001), and minimal in those not experiencing remission (2.7-fold; P = not significant). The improvement in ß-cell function after IV glucose administration was not apparent until 12 months, significant only in those in full remission, and only ∼33% of that observed after oral glucose intake. Preintervention ß-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. CONCLUSIONS: Our data show the time course of changes in ß-cell function after RYGB. The improvement in ß-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.

Temporal Eating Patterns and Eating Windows among Adults with Overweight or Obesity.

We aim to describe temporal eating patterns in a population of adults with overweight or obesity. In this cross-sectional analysis, data were combined from two separate pilot studies during which participants entered the timing of all eating occasions (>0 kcals) for 10-14 days. Data were aggregated to determine total eating occasions, local time of the first and last eating occasions, eating window, eating midpoint, and within-person variability of eating patterns. Eating patterns were compared between sexes, as well as between weekday and weekends. Participants (n = 85) had a median age of 56 ± 19 years, were mostly female (>70%), white (56.5%), and had a BMI of 31.8 ± 8.0 kg/m2. The median eating window was 14 h 04 min [12 h 57 min-15 h 21 min], which was significantly shorter on the weekend compared to weekdays (p < 0.0001). Only 13.1% of participants had an eating window <12 h/d. Additionally, there was greater irregularity with the first eating occasion during the week when compared to the weekend (p = 0.0002). In conclusion, adults with overweight or obesity have prolonged eating windows (>14 h/d). Future trials should examine the contribution of a prolonged eating window on adiposity independent of energy intake.

Preintervention Clinical Determinants and Measured ß-Cell Function As Predictors of Type 2 Diabetes Remission After Roux-en-Y Gastric Bypass Surgery.

BACKGROUND: Bariatric surgery results in improved glycemic control in individuals with type 2 diabetes. Single and clusters of clinical determinants have been identified as presurgery predictors of postsurgery diabetes remission. Our goal was to assess whether the addition of measured preoperative ß-cell function would improve established clinical models of prediction of diabetes remission. RESEARCH DESIGN AND METHODS: Presurgery clinical characteristics, metabolic markers, and ß-cell function after oral and intravenous (IV) glucose challenges were assessed in 73 individuals with severe obesity and type 2 diabetes and again 1 year after gastric bypass surgery. Single and multivariate analyses were conducted with preoperative variables to determine the best predictive models of remission. RESULTS: Presurgery ß-cell glucose sensitivity, a surrogate of ß-cell function, was negatively correlated with known diabetes duration, HbA1c, insulin use, and the diabetes remission scores DiaRem and advanced (Ad)-DiaRem (all P < 0.001). Measured ß-cell function after oral glucose was 1.6-fold greater than after the IV glucose challenge and more strongly correlated with preoperative clinical and metabolic characteristics. The addition of preoperative ß-cell function to clinical models containing well-defined diabetes remission scores did not improve the model's ability to predict diabetes remission after Roux-en-Y gastric bypass. CONCLUSIONS: The addition of measured ß-cell function does not add predictive value to defined clinical models of diabetes remission 1 year after surgical weight loss.

A Smartphone Intervention to Promote Time Restricted Eating Reduces Body Weight and Blood Pressure in Adults with Overweight and Obesity: A Pilot Study.

The goal of this study was to test the feasibility of time restricted eating (TRE) in adults with overweight and obesity. Participants (n = 50) logged all eating occasions (>0 kcal) for a 2-week run-in period using a smartphone application. Participants with eating duration ≥14 h enrolled in an open label, non-randomized, prospective 90-day TRE intervention, with a self-selected reduced eating window of 10 h. No dietary counseling was provided. Changes in anthropometrics, eating patterns and adherence after TRE were analyzed using t-tests or Wilcoxon Rank-Sum Test. The mean duration of the baseline eating window was 14 h 32 m ± 2 h 36 m (n = 50) with 56% of participants with duration ≥14 h. TRE participants (n = 16) successfully decreased their eating window from 16 h 04 m ± 1 h 24 m to 11 h 54 m ± 2 h 06 m (p < 0.001), and reduced the number of daily eating occasions by half (p < 0.001). Adherence to logging and to the reduced eating window was 64% ± 22% and 47% ± 19%, respectively. TRE resulted in decreases in body weight (-2.1 ± 3.0 kg, p = 0.017), waist circumference (-2.2 ± 4.6 cm, p = 0.002) and systolic blood pressure (-12 ± 11 mmHg, p = 0.002). This study demonstrates the feasibility and efficacy of TRE administered via a smartphone, in adults with overweight and obesity.

Anthropometrics by Three-Dimensional Photonic Scanner in Patients with Obesity Before and After Bariatric Surgery.

BACKGROUND: We studied body composition by three-dimensional photonic scanning (3DPS) and metabolic biomarkers in a large ethnically diverse cohort of individuals with severe obesity before and after weight loss by Roux-en-Y gastric bypass (RYGB) or adjustable gastric banding (AGB) surgery. MATERIALS AND METHODS: Male and female participants (n = 95) underwent 3DPS testing in the weeks preceding bariatric surgery (baseline), and 1 year after either RYGB (n = 34) or AGB (n = 9). RESULTS: Principal component analysis showed that A1C and HDL cholesterol clustered with waist-to-hip ratio (WHR). Both RYGB and AGB surgeries led to similar improvements in A1C and lipids after 1 year. RYGB led to greater decreases in body weight, and in most anthropometric measures, compared with AGB at 1 year. However, after accounting for weight loss differences, RYGB and AGB groups did not differ in regional decreases in circumferences or volumes; the exception was a greater reduction in lean mass in RYGB compared with AGB. CONCLUSION: Distribution of weight loss, assessed by 3DPS, did not differ between RYGB and AGB, but surgery type predicted change in lean mass at 1 year.

Leveraging phytochemicals: the plant phylogeny predicts sources of novel antibacterial compounds.

AIM: The goal of this study was to use phylogenetic evidence to determine plant families with high representation of antibacterial activity and identify potential sources to focus on for antibacterial drug discovery. MATERIALS & METHODS: We reconstructed the molecular phylogeny of plant taxa with antibacterial activity and mapped antibacterial mechanisms of action on the phylogeny. RESULTS: The phylogeny highlighted seven plant families (Combretaceae, Cupressaceae, Fabaceae, Lamiaceae, Lauraceae, Myrtaceae and Zingiberaceae) with disproportionately represented antibacterial activity. Phytochemicals produced were primarily involved in the disruption of the bacterial cell wall/membrane and inhibition of quorum sensing/biofilm production. CONCLUSION: The study provides phylogenetic evidence of seven plant families that should be examined as promising leads for novel antibacterial development.

Primary adenocarcinoma of cutaneous vesicostomy 40 years later: a rare case.

We present a case of adenocarcinoma developing at the vesicocutaneous edge of a vesicostomy, 40 years after it was created, in a patient who underwent cadaveric kidney transplant. Although transitional and squamous cell carcinoma of a vesicostomy have been reported, to our knowledge, the presence of adenocarcinoma at the vesicostomy edge has not been reported previously.