What can functional brain imaging teach us about remission of type 2 diabetes?

Aims: With a paradigm shift in attitudes towards type 2 diabetes (T2D), ‘weight loss responsive’ diabetes is now thought of as a curable disease state. As a result, national programmes are being orchestrated to induce T2D remission soon after diagnosis with aggressive dietary interventions—such as very low‐calorie diets (VLCD). However, dietary interventions to achieve weight loss and diabetes remission lack the same long‐term sustainability and cardiovascular risk reduction evidence as bariatric surgery. This review aims to explore how brain imaging has contributed to our understanding of human eating behaviours and how neural correlates are affected by T2D. Methods: We summarise functional MRI (fMRI) studies looking at human eating behaviour and obesity. We explore how these neural correlates are affected by insulin resistance and T2D itself as well as its different treatment approaches. Finally, we comment on the need for more personalised approaches to maintaining metabolic health and how fMRI studies may inform this. Conclusion: fMRI studies have helped to fashion our understanding of the neurobiology of human appetite and obesity. Improving our understanding of the neural implications of T2D that promote disadvantageous eating behaviours will enable prevention of disease as well as mitigation against a vicious cycle of metabolic dysfunction and associated cognitive complications

Mechanisms of Action of Bariatric Surgery on Body Weight Regulation

Bariatric surgery is an effective treatment modality for obesity and obesity-associated complications. Weight loss after bariatric surgery was initially attributed to anatomic restriction or reduced energy absorption, but now it is understood that surgery treats obesity by influencing the subcortical areas of the brain to lower adipose tissue mass. There are three major phases of this process: initially the weight loss phase, followed by a phase where weight loss is maintained, and in a subset of patients a phase where weight is regained. These phases are characterized by altered appetitive behavior together with changes in energy expenditure. The mechanisms associated with the rearrangement of the gastrointestinal tract include central appetite control, release of gut peptides, change in microbiota and bile acids. However, the exact combination and timing of signals remain largely unknown. [Abstract copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Harnessing the Melanocortin System in the control of food intake and glucose homeostasis

The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.</p

Mechanisms of weight loss after obesity surgery

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but have since been linked to reduced appetitive behaviour and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surger

Manipulation of Post-Prandial Hyperglycaemia in Type 2 Diabetes: An Update for Practitioners

This review paper explores post-prandial glycemia in type 2 diabetes. Post-prandial glycemia is defined as the period of blood glucose excursion from immediately after the ingestion of food or drink to 4 to 6 hours after the end of the meal. Post-prandial hyperglycemia is an independent risk factor for cardiovascular disease with glucose "excursions" being more strongly associated with markers of oxidative stress than the fasting or pre-prandial glucose level. High blood glucose is a major promoter of enhanced free radical production and is associated with the onset and progression of type 2 diabetes. Oxidative stress impairs insulin action creating a vicious cycle where repeated post-prandial glucose spikes are key drivers in the pathogenesis of the vascular complications of type 2 diabetes, both microvascular and macrovascular. Some authors suggest post-prandial hyperglycemia is the major cause of death in type 2 diabetes. Proper management of post-prandial hyperglycemia could yield up to a 35% cut in overall cardiovascular events, and a 64% cut in myocardial infarction. The benefits of managing post-prandial hyperglycemia are similar in magnitude to those seen in type 2 diabetes patients receiving secondary prevention with statins - prevention which today is regarded as fundamental by all practitioners. Given all the evidence surrounding the impact of post-prandial glycemia on overall outcome, it is imperative that any considered strategy for the management of type 2 diabetes should include optimum dietary, pharma, and lifestyle interventions that address glucose excursion. Achieving a low post-prandial glucose response is key to prevention and progression of type 2 diabetes and cardiometabolic diseases. Further, such therapeutic interventions should be sustainable and must benefit patients in the short and long term with the minimum of intrusion and side effects. This paper reviews the current literature around dietary manipulation of post-prandial hyperglycemia, including novel approaches. A great deal of further work is required to optimize and standardize the dietary management of post-prandial glycemia in type 2 diabetes, including consideration of novel approaches that show great promise. [Abstract copyright: © 2024 Shibib et al.

Impact of insulin sensitization on metabolic and fertility outcomes in women with polycystic ovary syndrome and overweight or obesity—A systematic review, meta‐analysis, and meta‐regression

Summary: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive‐age women. This systematic review, meta‐analysis, and meta‐regression aims to compare the effect of insulin sensitizer pharmacotherapy on metabolic and reproductive outcomes in women with PCOS and overweight or obesity. We searched online databases MEDLINE via OVID, EMBASE, Clinicaltrials.gov, and EudraCT for trials published from inception to November 13, 2023. Inclusion criteria were double‐blind, randomized controlled trials in women diagnosed with PCOS, body mass index (BMI) ≥ 25 kg/m2, which reported metabolic or reproductive outcomes. The intervention was insulin sensitization pharmacotherapy versus placebo or other agents. The primary outcomes were changes from baseline BMI, fasting blood glucose, and menstrual frequency. Nineteen studies were included in this review. Metformin had the most significant effect on the fasting plasma glucose and body mass index. Insulin sensitizer pharmacotherapy significantly reduced fasting plasma glucose, body mass index, fasting serum insulin, HOMA‐IR, sex hormone binding globulin, and total testosterone, but the effect size was small. There was a lack of menstrual frequency and live birth data. The results indicate a role for insulin sensitizers in improving the metabolic and, to a lesser degree, reproductive profile in these women. Further research should examine insulin sensitizers' effects on objective measures of fecundity

Bariatric surgery tourism in the COVID-19 era

Background: Since the start of the Covid-19 pandemic primary and secondary health care services in Northern Ireland have observed an increase in the number of patients who have had bariatric surgery outside of the UK. This study sought to estimate the frequency of bariatric surgery tourism and to audit indications, blood monitoring and medical complications.Methods: All primary care centres within the Western Health Social Care Trust (WHSCT) were invited to document the number of patients undergoing bariatric surgery between January 1, 2017 and December 31, 2022. For one primary care centre, patients who underwent bariatric surgery were assessed against the National Institute of Health and Clinical Excellence (NICE) guideline indications for bariatric surgery. In addition, the blood monitoring of these patients was audited against the British Obesity and Metabolic Surgery Society (BOMSS) guidelines for up to two years following surgery. Medical contacts for surgical complications of bariatric surgery were recorded.Results: Thirty-five of 47 (74.5%) GP surgeries replied to the survey, representing 239,961 patients among 325,126 registrations (73.8%). In the six year study period 463 patients had reported having bariatric surgery to their GP. Women were more likely to have had bariatric surgery than men (85.1% versus 14.9%). There was a marked increase in the number of patients undergoing bariatric surgery with each year of the study (p&lt;0.0001 chi square for trend). Twenty-one of 47 patients (44.7%) evaluated in one primary care centre fulfilled NICE criteria for bariatric surgery. The level of three-month monitoring ranged from 23% (for vitamin D) to 89% (electrolytes), but decreased at two years to 9% (vitamin D) and 64% (electrolytes and liver function tests). Surgical complication prevalence from wound infections was 19% (9 of 44). Antidepressant medications were prescribed for 23 of 47 patients (48.9%).Conclusions: The WHSCT has experienced a growing population of patients availing of bariatric surgery outside of the National Health Service. In view of this and the projected increase in obesity prevalence, a specialist obesity management service is urgently required in Northern Ireland.</p