Physiology of the Weight-Reduced State and Its Impact on Weight Regain.

Obesity is a chronic disease characterized by long duration, slow progression, and periods of remission and relapses. Despite the development of effective medical and surgical interventions and millions of people conducting tremendous personal efforts to manage their weight every year, recidivism remains a significant barrier to attaining long-term weight maintenance. This review aimed to explain the underlying physiology of the weight-reduced state including changes in energy balance, adipose tissue, genetic, environmental, and behavioral factors that may predispose individuals to weight regain following weight loss.

Changes in physical activity during COVID-19 pandemic among Saudi Arabians: Results from a cross-sectional study.

Background and Aims: The COVID-19 pandemic and the resultant change in sedentary behaviors have had immense health, economic, and social implications globally. As governments worldwide imposed lockdowns and curfews, the amount of time spent indoors greatly increased. This lead to a dramatic change in physical activity (PA) levels and profound consequences on daily routines. Our study aimed to investigate patterns of PA during the COVID-19 pandemic among adults residing in Saudi Arabia. Methods: This cross-sectional survey-based study aimed to investigate patterns of PA during the COVID-19 pandemic among adults residing in Saudi Arabia. The International Physical Activity Questionnaire was utilized to measure participants' PA levels between April 2021 and May 2021. Participants were then classified into three groups according to their PA level, and their PA levels and sedentary behaviors were analyzed. Results: We surveyed 463 participants, 315 (68%) of which were female and 134 (32%) of which were male with a median age of 23 (interquartile range, 21-35) years. Moderate-to-high PA was reported by 257 (55.7%) of the participants. There was a significant decrease in PA during the COVID-19 pandemic and resultant lockdowns among the participants (p = 0.04), with higher rates of sedentary behavior among males than females (p = 0.14). Conclusions: The decline in PA is a profound challenge of the COVID-19 pandemic that needs to be addressed by health practitioners and policymakers. Our study highlights the decline in PA levels seen during the COVID-19 pandemic and the importance of promotional programs and interventions to increase PA among the Saudi Arabian population without compromising the essential health restrictions and social distancing.

Use of primary bariatric surgery among patients with obesity and diabetes. Insights from the Diabetes Collaborative Registry.

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m2), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy.

Canagliflozin Prevents Hyperglycemia-Associated Muscle Extracellular Matrix Accumulation and Improves the Adaptive Response to Aerobic Exercise.

Chronic hyperglycemia is associated with low response to aerobic exercise training in rodent models and humans, including reduced aerobic exercise capacity and impaired oxidative remodeling in skeletal muscle. Here, we investigated whether glucose lowering with the sodium-glucose cotransporter 2 inhibitor (SGLT2i), canagliflozin (Cana; 30 mg/kg/day), could restore exercise training response in a model of hyperglycemia (low-dose streptozotocin [STZ]). Cana effectively prevented increased blood glucose in STZ-treated mice. After 6 weeks of voluntary wheel running, Cana-treated mice displayed improvements in aerobic exercise capacity, higher capillary density in striated muscle, and a more oxidative fiber-type in skeletal muscle. In contrast, these responses were blunted or absent in STZ-treated mice. Recent work implicates glucose-induced accumulation of skeletal muscle extracellular matrix (ECM) and hyperactivation of c-Jun N-terminal kinase (JNK)/SMAD2 mechanical signaling as potential mechanisms underlying poor exercise response. In line with this, muscle ECM accretion was prevented by Cana in STZ-treated mice. JNK/SMAD2 signaling with acute exercise was twofold higher in STZ compared with control but was normalized by Cana. In human participants, ECM accumulation was associated with increased JNK signaling, low VO2peak, and impaired metabolic health (oral glucose tolerance test-derived insulin sensitivity). These data demonstrate that hyperglycemia-associated impairments in exercise adaptation can be ameliorated by cotherapy with SGLT2i.

Caring for Young Adults With Diabetes in the Adult Care Setting: Summary of a Multidisciplinary Roundtable.

Aims: A multidisciplinary team of clinicians and researchers, patients and family members, and representative from national advocacy groups and research organization met to review the literature, highlight gaps, and identify best practices to improve adult care delivery for young adults (YA) with diabetes. Methods: The participants prepared presentations in advance, rotated through sessions, and contributed to group discussions in three areas: physical health, mental health, and quality of life (QoL). Session moderators and scribes used thematic analysis to summarize discussions for each topic. Results: Thematic analysis revealed four foci for addressing physical health, mental health and QoL: 1) best practices to facilitate the process of transfer; 2) age-specific curricula and guidelines for prevention and management of comorbidities and complications; 3) collaboration with behavioral health clinicians to address diabetes distress and mental health disorders; and 4) research on the impact of diabetes on QoL in YA. Conclusion: There was substantial interest and need among adult clinicians to work in concert with pediatric and mental health professionals to identify best practices and future directions to improve healthcare process and diabetes-related outcome measures in YA with diabetes.

Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise.

Increased aerobic exercise capacity, as a result of exercise training, has important health benefits. However, some individuals are resistant to improvements in exercise capacity, probably due to undetermined genetic and environmental factors. Here, we show that exercise-induced improvements in aerobic capacity are blunted and aerobic remodelling of skeletal muscle is impaired in several animal models associated with chronic hyperglycaemia. Our data point to chronic hyperglycaemia as a potential negative regulator of aerobic adaptation, in part, via glucose-mediated modifications of the extracellular matrix, impaired vascularization and aberrant mechanical signalling in muscle. We also observe low exercise capacity and enhanced c-Jun N-terminal kinase activation in response to exercise in humans with impaired glucose tolerance. Our work indicates that current shifts in dietary and metabolic health, associated with increasing incidence of hyperglycaemia, might impair muscular and organismal adaptations to exercise training, including aerobic capacity as one of its key health outcomes.

Management of Diabetes in Patients Undergoing Bariatric Surgery.

PURPOSE OF REVIEW: The number of bariatric surgeries for patients with type 1 or type 2 diabetes continues to grow. Clinicians are challenged to choose therapies that reach glycemic targets without inducing adverse effects in post-bariatric patients without published guidelines. This review evaluates data supporting the best strategies for diabetes management in patients undergoing bariatric surgery. RECENT FINDINGS: Though few clinical trials have evaluated the safety and effectiveness of different glucose-lowering therapies following bariatric surgery, remission of diabetes or reduced medications is an established benefit of bariatric surgery. Adverse events including diabetic ketoacidosis in post-bariatric patients on sodium-glucose co-transporter 2 (SGLT2) inhibitors or inadequate insulin have been reported in patient's with both type 1 and type 2 diabetes. Metformin, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, insulin, and sulfonylureas have been used successfully in the perioperative period for other surgeries and guidelines recommend adjusting the doses of these medications especially in the perioperative period. Clinicians should favor weight-neutral or weight-loss promoting therapies in post-bariatric surgery patients such as medical nutrition therapy, metformin, GLP-1 agonists, SGLT2 inhibitors, and DPP-4 inhibitors.

Intensive multidisciplinary weight management in patients with type 1 diabetes and obesity: A one-year retrospective matched cohort study.

AIMS: Recent studies report that approximately 50% of patients with type 1 diabetes (T1D) are overweight or obese. This work studies the effects of intensive multidisciplinary weight management (IMWM) in patients with T1D and obesity. METHODS: We retrospectively evaluated 68 patients with T1D and obesity who enrolled in a 12-week IMWM program (IMWM cohort: mean age, 42 ± 11 years; HbA1c, 8.3% ± 1.0%; body weight, 104.3 ± 18.2 kg; BMI, 36.2 ± 4.9 kg/m2 ). We matched them 1:1 with a similar cohort of patients receiving standard care (SC cohort: mean age, 42 ± 12 years; HbA1c, 8.3% ± 1.0%; body weight, 102.4 ± 17.9 kg; BMI, 36.1 ± 4.7 kg/m2 ). Data were collected at baseline and at 12 months. RESULTS: Participants in the IMWM cohort had a body weight change of -6.6 ± 1.8 kg or -6.4% ± 1.6% of their initial body weight, while participants in the SC cohort had no change (P < 0.01 for group*time interaction). Participants in the IMWM cohort had a change in HbA1c of -0.4% ± 0.1% from baseline (P < 0.01), while participants in the SC cohort had no change. There was no difference in glycaemic control between cohorts at 12 months. Total daily insulin dose changed by -5.9 ± 1.8 units/d from baseline in the IMWM cohort while there was no change in the SC cohort (P < 0.01 for group*time interaction). CONCLUSIONS: In comparison to standard care, patients with T1D and obesity who participated in an IMWM programme achieved significant weight loss and significant reduction in daily insulin dose at 1 year. Weight reduction was associated with improvements in glycaemic control compared to baseline.

Lead (Pb) exposure promotes diabetes in obese rodents.

BACKGROUND: Pb (lead) exposure occurs at elevated frequency in urban inner city populations that also have high rates of obesity and diabetes. OBJECTIVES: To determine if Pb can promote the development of diabetes in a setting of obesity, we examined the effect of Pb exposure on glucose metabolism in a rodent model of obesity. METHODS: Adult female ZDF rats were exposed to Pb in drinking water for 24 weeks. Fasting blood glucose, insulin, and glucose tolerance were measured at regular intervals. Expression of hepatic gluconeogenic genes was measured in exposed and control animals and in cultured hepatoma cells treated with Pb. RESULTS: Pb exposure induced fasting hyperglycemia after 8 weeks and glucose intolerance after 12 weeks of exposure. In addition, Pb-exposed animals showed elevated hepatic triglyceride levels and increased expression of the gluconeogenic genes PEPCK and glucose-6-phosphatase. In cultured rat hepatoma cells treatment with Pb stimulated PEPCK and glucose-6-phosphatase gene expression, suggesting a possible direct effect of Pb on hepatic gluconeogenic gene expression. CONCLUSIONS: In the setting of obesity, Pb exposure is prodiabetic, causing fasting hyperglycemia and glucose intolerance in rats. A contributing factor to the metabolic effects of Pb may be the direct stimulation of hepatic gluconeogenic gene expression.

The impact of bariatric surgery on inflammation: quenching the fire of obesity?

PURPOSE OF REVIEW: Numerous lines of evidence support the likelihood that inflammation drives the transition from obese/metabolically healthy to obese/type 2 diabetes (T2D). Given the temporal flexibility of inflammation in obesity-associated T2D, investigators have hypothesized that a precipitous drop in diabetogenic cytokines is critical for rapid 'T2D remission' following surgery but prior to significant weight loss. We review the evidence that changes in diabetogenic cytokines play a role in outcomes of bariatric surgery, including improved glycemic control. RECENT FINDINGS: A 2016 indication for bariatric surgery to treat T2D integrates the large body of data showing rapid metabolic improvement. Parameters that account for improved glycemic control prior to significant weight loss, T2D recidivism over the long term, or failure of surgery to remit T2D in some patients are incompletely understood. SUMMARY: We review the evidence that changes in diabetogenic cytokines play a role in outcomes of bariatric surgery, including improved glycemic control. We brainstorm future research directions that may improve surgical results.