Nutritional Challenges and Treatment After Bariatric Surgery.

Bariatric surgery is an important weight loss tool in individuals with severe obesity. It is currently the most effective long-term weight loss treatment that lowers obesity-related comorbidities. It also has significant physiological and nutritional consequences that can result in gastrointestinal complications and micronutrient deficiencies. After gastric bypass, common clinical events that negatively affect nutritional status include malabsorption, dumping syndrome, kidney stones, altered intestinal bile acid availability, bowel obstruction, ulcer, gastroesophageal reflux, and bacterial overgrowth. Risk factors for poor nutritional status and excessive loss of lean body mass and bone include reduced dietary quality and inadequate intake, altered nutrient absorption, and poor patient compliance with nutrient supplementation. There are unique concerns in adolescents, older individuals, and individuals who become pregnant postoperatively. With careful management, health-care professionals can assist with long-term weight loss success and minimize the risk of acute and long-term nutrition complications after bariatric surgery.

Diet and Meal Pattern Determinants of Glucose Levels and Variability in Adults with and without Prediabetes or Early-Onset Type 2 Diabetes: A Pilot Study.

This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with dysglycemia (D-GLYC) and 14 with normoglycemia (N-GLYC). We hypothesized that a prolonged eating window and late eating occasions (EOs), along with a higher dietary carbohydrate intake, would result in higher glucose levels and glucose variability (GV). General linear models were run with meal timing with time-stamped photographs in real time, and diet composition by dietary recalls, and their variability (SD), as predictors and glucose variables (mean glucose, mean amplitude of glucose excursions [MAGE], largest amplitude of glucose excursions [LAGE] and GV) as dependent variables. After adjusting for calories and nutrients, a later eating midpoint predicted a lower GV (ß = -2.3, SE = 1.0, p = 0.03) in D-GLYC, while a later last EO predicted a higher GV (ß = 1.5, SE = 0.6, p = 0.04) in N-GLYC. A higher carbohydrate intake predicted a higher MAGE (ß = 0.9, SE = 0.4, p = 0.02) and GV (ß = 0.4, SE = 0.2, p = 0.04) in N-GLYC, but not D-GLYC. In summary, our data suggest that meal patterns interact with dietary composition and should be evaluated as potential modifiable determinants of glucose in adults with and without dysglycemia. Future research should evaluate causality with controlled diets.

Long-term sustained effects of the Look AHEAD lifestyle intervention on body composition among adults with type 2 diabetes.

OBJECTIVE: The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization. METHODS: Participants were a subset of enrollees in the Look AHEAD dual-energy x-ray absorptiometry substudy who completed the final visit, composed of men (DSE = 99; ILI = 94) and women (DSE = 134; ILI = 135) with type 2 diabetes and mean (SD) age 57.2 (6.4) years and BMI 34.9 (5.1) kg/m2 at randomization. Dual-energy x-ray absorptiometry measured total and regional fat and lean masses at randomization, at Years 1, 4, and 8, and at the final visit. Linear mixed-effects regressions were applied with adjustment for group, clinic, sex, age, race/ethnicity, and baseline body composition. RESULTS: Weight and most body compartments were reduced by 2% to 8% (and BMI 4%) in ILI versus DSE in men but not women. ILI-induced loss of lean tissue did not show a lower percent lean mass versus DSE at 16 years after randomization. CONCLUSION: ILI-related changes in weight, fat, and lean mass were detectable 12 to 16 years after randomization in men but, for unknown reasons, not in women. There was no evidence that the intervention led to a disproportionate loss of lean mass by the end of the study.

Remission of type 2 diabetes: always more questions, but enough answers for action.

The concept of type 2 diabetes remission is evolving rapidly, and gaining wide public and professional interest, following demonstration that with substantial intentional weight loss almost nine in ten people with type 2 diabetes can reduce their HbA1c level below the diagnostic criterion (48 mmol/mol [6.5%]) without glucose-lowering medications, and improve all features of the metabolic syndrome. Pursuing nomoglycaemia with older drugs was dangerous because of the risk of side effects and hypoglycaemia, so the conventional treatment target was an HbA1c concentration of 53 mmol/mol (7%), meaning that diabetes was still present and allowing disease progression. Newer agents may achieve a normal HbA1c safely and, by analogy with treatments that send cancers or inflammatory diseases into remission, this might also be considered remission. However, although modern glucagon-like peptide-1 receptor agonists and related medications are highly effective for weight loss and glycaemic improvement, and generally safe, many people do not want to take drugs indefinitely, and their cost means that they are not available across much of the world. Therefore, there are strong reasons to explore and research dietary approaches for the treatment of type 2 diabetes. All interventions that achieve sustained weight loss of >10-15 kg improve HbA1c, potentially resulting in remission if sufficient beta cell capacity can be preserved or restored, which occurs with loss of the ectopic fat in liver and pancreas that is found with type 2 diabetes. Remission is most likely with type 2 diabetes of short duration, lower HbA1c and a low requirement for glucose-lowering medications. Relapse is likely with weight regain and among those with a poor beta cell reserve. On current evidence, effective weight management should be provided to all people with type 2 diabetes as soon as possible after diagnosis (or even earlier, at the stage of prediabetes, defined in Europe, Australasia, Canada [and most of the world] as ≥42 and <48 mmol/mol [≥6.0 and <6.5%], and in the USA as HbA1c ≥39 and <48 mmol/mol [≥5.7 and <6.5%]). Raising awareness among people with type 2 diabetes and their healthcare providers that remission is possible will enable earlier intervention. Weight loss of >10 kg and remission lasting 1-2 years may also delay vascular complications, although more evidence is needed. The greatest challenge for research is to improve long-term weight loss maintenance, defining cost-effective approaches tailored to the preferences and needs of people living with type 2 diabetes.

Metabolite signature of diabetes remission in individuals with obesity undergoing weight loss interventions.

OBJECTIVE: This observational study investigated metabolomic changes in individuals with type 2 diabetes (T2D) after weight loss. We hypothesized that metabolite changes associated with T2D-relevant phenotypes are signatures of improved health. METHODS: Fasting plasma samples from individuals undergoing bariatric surgery (n = 71 Roux-en-Y gastric bypass [RYGB], n = 22 gastric banding), lifestyle intervention (n = 66), or usual care (n = 14) were profiled for 139 metabolites before and 2 years after weight loss. Principal component analysis grouped correlated metabolites into factors. Association of preintervention metabolites was tested with preintervention clinical features and changes in T2D markers. Association between change in metabolites/metabolite factors and change in T2D remission markers, homeostasis model assessment of ß-cell function, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) was assessed. RESULTS: Branched-chain amino acids (BCAAs) were associated with preintervention adiposity. Changes in BCAAs (valine, leucine/isoleucine) and branched-chain ketoacids were positively associated with change in HbA1c (false discovery rate q value ≤ 0.001) that persisted after adjustment for percentage weight change and RYGB (p ≤ 0.02). In analyses stratified by RYGB or other weight loss method, some metabolites showed association with non-RYGB weight loss. CONCLUSIONS: This study confirmed known metabolite associations with obesity/T2D and showed an association of BCAAs with HbA1c change after weight loss, independent of the method or magnitude of weight loss.

Chronic Insufficient Sleep in Women Impairs Insulin Sensitivity Independent of Adiposity Changes: Results of a Randomized Trial.

OBJECTIVE: Insufficient sleep is associated with type 2 diabetes, yet the causal impact of chronic insufficient sleep on glucose metabolism in women is unknown. We investigated whether prolonged mild sleep restriction (SR), resembling real-world short sleep, impairs glucose metabolism in women. RESEARCH DESIGN AND METHODS: Women (aged 20-75 years) without cardiometabolic diseases and with actigraphy-confirmed habitual total sleep time (TST) of 7-9 h/night were recruited to participate in this randomized, crossover study with two 6-week phases: maintenance of adequate sleep (AS) and 1.5 h/night SR. Outcomes included plasma glucose and insulin levels, HOMA of insulin resistance (HOMA-IR) values based on fasting blood samples, as well as total area under the curve for glucose and insulin, the Matsuda index, and the disposition index from an oral glucose tolerance test. RESULTS: Our sample included 38 women (n = 11 postmenopausal women). Values are reported with ±SEM. Linear models adjusted for baseline outcome values demonstrated that TST was reduced by 1.34 ± 0.04 h/night with SR versus AS (P < 0.0001). Fasting insulin (ß = 6.8 ± 2.8 pmol/L; P = 0.016) and HOMA-IR (ß = 0.30 ± 0.12; P = 0.016) values were increased with SR versus AS, with effects on HOMA-IR more pronounced in postmenopausal women compared with premenopausal women (ß = 0.45 ± 0.25 vs. ß = 0.27 ± 0.13, respectively; P for interaction = 0.042). Change in adiposity did not mediate the effects of SR on glucose metabolism or change results in the full sample when included as a covariate. CONCLUSIONS: Curtailing sleep duration to 6.2 h/night, reflecting the median sleep duration of U.S. adults with short sleep, for 6 weeks impairs insulin sensitivity, independent of adiposity. Findings highlight insufficient sleep as a modifiable risk factor for insulin resistance in women to be targeted in diabetes prevention efforts.

Racial and Ethnic Disparities in Glycemic Control Among Insured US Adults.

Importance: Poor access to care and lack of health insurance are important contributors to disparities in glycemic control. However expanding health insurance coverage may not be enough to fully address the high burden of poor glycemic control for some groups. Objective: To characterize racial and ethnic disparities in glycemic control among adults with private and public insurance in the US over a 15-year timeframe and to evaluate whether social, health care, and behavioral or health status factors attenuate estimates of disparities. Design, Setting, and Participants: This cross-sectional study used data from the National Health and Nutrition Examination Survey from 2003 to 2018. Participants included Hispanic or Latino, non-Hispanic Black, and non-Hispanic White adults aged 25 to 80 years with self-reported diabetes and health insurance. Data were analyzed from January 15 to August 23, 2023. Exposure: Participants self-identified as Hispanic or Latino, non-Hispanic Black, or non-Hispanic White. Main Outcomes and Measures: The main outcome, poor glycemic control, was defined as glycated hemoglobin A1c (HbA1c) of 7.0% or greater. Information about social (education, food security, and nativity), health care (insurance type, routine place for health care, insurance gap in past year, and use of diabetes medications), and behavioral or health status (years with diabetes, waist circumference, and smoking) factors were collected via questionnaires. Results: A total of 4070 individuals (weighted mean [SE] age, 61.4 [0.27] years; 1970 [weighted proportion, 49.3%] were women) were included, representing 16 337 362 US adults, including 1146 Hispanic or Latino individuals (weighted proportion, 13.2%), 1196 non-Hispanic Black individuals (weighted proportion, 15.7%), and 1728 non-Hispanic White individuals (weighted proportion, 71.1%). In models adjusted for age, sex, and survey year, Hispanic or Latino and non-Hispanic Black individuals had significantly higher odds of poor glycemic control than non-Hispanic White individuals (Hispanic or Latino: odds ratio [OR], 1.46; 95% CI, 1.16-1.83; Black: OR, 1.28; 95% CI, 1.04-1.57). There was some attenuation after adjustment for social factors, especially food security (Hispanic or Latino: OR, 1.39; 95% CI, 1.08-1.81); Black: OR, 1.39; 95% CI, 1.08-1.81). However, accounting for health care and behavioral or health status factors increased disparities, especially for Hispanic or Latino individuals (OR, 1.63; 95% CI, 1.24-2.16), with racial and ethnic disparities persisting even among those with private insurance (OR, 1.66; 95% CI, 1.10-2.52). Conclusions and Relevance: In this cross-sectional study of insured adults with diabetes in the US, disparities in poor glycemic control persisted despite adjustment for social, health care, and behavioral factors. Research is needed to identify the barriers contributing to poor control even in populations with access to care.

Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity.

Bassoon (BSN) is a component of a hetero-dimeric presynaptic cytomatrix protein that orchestrates neurotransmitter release with Piccolo (PCLO) from glutamatergic neurons throughout the brain. Heterozygous missense variants in BSN have previously been associated with neurodegenerative disorders in humans. We performed an exome-wide association analysis of ultra-rare variants in about 140,000 unrelated individuals from the UK Biobank to search for new genes associated with obesity. We found that rare heterozygous predicted loss of function (pLoF) variants in BSN are associated with higher BMI with p-value of 3.6e-12 in the UK biobank cohort. Additionally, we identified two individuals (one of whom has a de novo variant) with a heterozygous pLoF variant in a cohort of early onset or extreme obesity and report the clinical histories of these individuals with non-syndromic obesity with no history of neurobehavioral or cognitive disability. The BMI association was replicated in the All of Us whole genome sequencing data. Heterozygous pLoF BSN variants constitute a new etiology for obesity.

Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes.

Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as MET's primary target. Here, we explored the effect of MET on the gut glucose transport machinery. Using human enterocytes (Caco-2/TC7 cells) in vitro, we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of glucose, without changes in the mRNA levels of the transporter. Administered 1 h before a glucose challenge in rats (Wistar, GK), C57BL6 mice and mice pigs, oral MET reduced the post-prandial glucose response (PGR). This effect was abrogated in SGLT1-KO mice. MET also reduced the luminal clearance of 2-(18F)-fluoro-2-deoxy-D-glucose after oral administration in rats. In conclusion, oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of SGLT1 in enterocytes, which may contribute to the clinical effects of the drug.

Time-restricted eating to improve cardiometabolic health: The New York Time-Restricted EATing randomized clinical trial - Protocol overview.

Re-aligning eating patterns with biological rhythm can reduce the burden of metabolic syndrome in older adults with overweight or obesity. Time-restricted eating (TRE) has been shown to result in weight loss and improved cardiometabolic health while being less challenging than counting calories. The New York Time-Restricted EATing study (NY-TREAT) is a two-arm, randomized clinical trial (RCT) that aims to examine the efficacy and sustainability of TRE (eating window ≤10 h/day) vs. a habitual prolonged eating window (HABIT, ≥14 h/day) in metabolically unhealthy midlife adults (50-75 years) with overweight or obesity and prediabetes or type 2 diabetes (T2D). Our primary hypothesis is that the TRE will result in greater weight loss compared to HABIT at 3 months. The efficacy of the TRE intervention on body weight, fat mass, energy expenditure, and glucose is tested at 3 months, and the sustainability of its effect is measured at 12 months, with ambulatory assessments of sleep and physical activity (ActiGraph), eating pattern (smartphone application), and interstitial glucose (continuous glucose monitoring). The RCT also includes state-of-the-art measurements of body fat (quantitative magnetic resonance), total energy expenditure (doubly-labelled water), insulin secretion, insulin resistance, and glucose tolerance. Adherence to self-monitoring and reduced eating window are monitored remotely in real-time. This RCT will provide further insight into the effects of TRE on cardiometabolic health in individuals with high metabolic risk. Sixty-two participants will be enrolled, and with estimated 30% attrition, 42 participants will return at 12 months. This protocol describes the design, interventions, methods, and expected outcomes. Clinical trial registration:NCT04465721 IRB: AAAS7791.

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.

Impact of COVID-19 on life experiences reported by a diverse cohort of older adults with diabetes and obesity.

OBJECTIVE: This study aimed to measure the impact of the COVID-19 pandemic on self-reported life experiences in older adults with diabetes and obesity. METHODS: Participants were surveyed in 2020 regarding negative and positive impacts of the pandemic across domains of personal, social, and physical experiences. A cumulative negative risk index (a count of all reported negative impacts of 46 items) and a positive risk index (5 items) were characterized in relation to age, sex, race/ethnicity, BMI, and multimorbidity. RESULTS: Response rate was high (2950/3193, 92%), average age was 76 years, 63% were women, and 39% were from underrepresented populations. Women reported more negative impacts than men (6.8 vs. 5.6; p < 0.001 [of 46 items]) as did persons with a greater multimorbidity index (p < 0.001). Participants reporting African American/Black race reported fewer negative impacts than White participants. Women also reported more positive impacts than men (1.9 vs. 1.6; p < 0.001 [of 5 items]). CONCLUSIONS: Older adults with diabetes and obesity reported more positive impacts of the pandemic than negative impacts, relative to the number of positive (or negative) items presented. Some subgroups experienced greater negative impacts (e.g., for women, a greater multimorbidity index). Efforts to reestablish personal, social, and physical health after the pandemic could target certain groups.

Data-driven subgroups of type 2 diabetes, metabolic response, and renal risk profile after bariatric surgery: a retrospective cohort study.

BACKGROUND: A novel data-driven classification of type 2 diabetes has been proposed to personalise anti-diabetic treatment according to phenotype. One subgroup, severe insulin-resistant diabetes (SIRD), is characterised by mild hyperglycaemia but marked hyperinsulinaemia, and presents an increased risk of diabetic nephropathy. We hypothesised that patients with SIRD could particularly benefit from metabolic surgery. METHODS: We retrospectively related the newly defined clusters with the response to metabolic surgery in participants with type 2 diabetes from independent cohorts in France (the Atlas Biologique de l'Obésite Sévère [ABOS] cohort, n=368; participants underwent Roux-en-Y gastric bypass or sleeve gastrectomy between Jan 1, 2006, and Dec 12, 2017) and Brazil (the metabolic surgery cohort of the German Hospital of San Paulo, n=121; participants underwent Roux-en-Y gastric bypass between April 1, 2008, and March 20, 2016). The study outcomes were type 2 diabetes remission and improvement of estimated glomerular filtration rate (eGFR). FINDINGS: At baseline, 34 (9%) of 368 patients, 314 (85%) of 368 patients, and 17 (5%) of 368 patients were classified as having SIRD, mild obesity-related diabetes (MOD), and severe insulin deficient diabetes (SIDD) in the ABOS cohort, respectively, and in the São Paulo cohort, ten (8%) of 121 patients, 83 (69%) of 121 patients, and 25 (21%) of 121 patients were classified as having SIRD, MOD, and SIDD, respectively. At 1 year, type 2 diabetes remission was reported in 26 (81%) of 32 and nine (90%) of ten patients with SIRD, 167 (55%) of 306 and 42 (51%) of 83 patients with MOD, and two (13%) of 16 and nine (36%) of 25 patients with SIDD, in the ABOS and São Paulo cohorts, respectively. The mean eGFR was lower in patients with SIRD at baseline and increased postoperatively in these patients in both cohorts. In multivariable analysis, SIRD was associated with more frequent type 2 diabetes remission (odds ratio 4·3, 95% CI 1·8-11·2; p=0·0015), and an increase in eGFR (mean effect size 13·1 ml/min per 1·73 m2, 95% CI 3·6-22·7; p=0·0070). INTERPRETATION: Patients in the SIRD subgroup had better outcomes after metabolic surgery, both in terms of type 2 diabetes remission and renal function, with no additional surgical risk. Data-driven classification might help to refine the indications for metabolic surgery. FUNDING: Agence Nationale de la Recherche, Investissement d'Avenir, Innovative Medecines Initiative, Fondation Cœur et Artères, and Fondation Francophone pour la Recherche sur le Diabète.

Eating breakfast is associated with weight loss during an intensive lifestyle intervention for overweight/obesity.

OBJECTIVE: This study examined whether breakfast consumption frequency (BCF) is associated with weight-loss outcomes in the Look AHEAD (Action for Health in Diabetes) trial. METHODS: Data from a subset of participants (n = 3,915) from Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) to diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, were analyzed. BCF was collected by yearly questionnaire. Multivariable linear regression models were used to estimate the association between average BCF and percentage weight change over 4 years, controlling for baseline sociodemographic, anthropometric, and diabetes-related variables. In separate models, adjustment for diet (n = 915) and physical activity level (n = 837) was performed in a subset of participants. RESULTS: Four-year average BCF was similar in DSE (n = 1,916) and ILI (n = 1,999) arms (p = 0.14). Each 1-day higher average BCF was associated with an additional 0.5% weight loss in the ILI arm (p < 0.0001) but not in the DSE arm (p = 0.58). This association in the ILI arm remained significant after adjustment for diet (p = 0.02) but not after adjustment for physical activity (p = 0.36). CONCLUSIONS: Breakfast consumption was associated with greater weight loss in the active treatment group of an ILI, which may be mediated by increased physical activity.

Time-restricted Eating for the Prevention and Management of Metabolic Diseases.

Time-restricted feeding (TRF, animal-based studies) and time-restricted eating (TRE, humans) are an emerging behavioral intervention approach based on the understanding of the role of circadian rhythms in physiology and metabolism. In this approach, all calorie intake is restricted within a consistent interval of less than 12 hours without overtly attempting to reduce calories. This article will summarize the origin of TRF/TRE starting with concept of circadian rhythms and the role of chronic circadian rhythm disruption in increasing the risk for chronic metabolic diseases. Circadian rhythms are usually perceived as the sleep-wake cycle and dependent rhythms arising from the central nervous system. However, the recent discovery of circadian rhythms in peripheral organs and the plasticity of these rhythms in response to changes in nutrition availability raised the possibility that adopting a consistent daily short window of feeding can sustain robust circadian rhythm. Preclinical animal studies have demonstrated proof of concept and identified potential mechanisms driving TRF-related benefits. Pilot human intervention studies have reported promising results in reducing the risk for obesity, diabetes, and cardiovascular diseases. Epidemiological studies have indicated that maintaining a consistent long overnight fast, which is similar to TRE, can significantly reduce risks for chronic diseases. Despite these early successes, more clinical and mechanistic studies are needed to implement TRE alone or as adjuvant lifestyle intervention for the prevention and management of chronic metabolic diseases.