Proposed mechanisms for bariatric surgery-induced improvement and resolution of clinical manifestations of type II diabetes
Ionson, Annaliese Claire
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At the 2nd Diabetes Surgical Summit in 2015, the world’s leading researchers and professionals in the field of diabetes, surgery, and public health gathered to develop new surgical treatment guidelines for diabetes. This summit led to the recommendation of bariatric surgery as an official treatment for type II diabetes, outlining that the surgery be considered for diabetic patients with a Body Mass Index (BMI) of 30, a much lower threshold BMI than that of typical bariatric surgery patients. Despite incontrovertible evidence that bariatric surgery can reverse the progression of diabetes and even cause remission, the physiological mechanisms chiefly responsible for these effects remain controversial. Peer-reviewed published literature was collected to examine the evidence for mechanisms responsible for metabolic improvements following bariatric surgery, especially Roux-en-Y gastric bypass. This review considered the effects of calorie restriction, appetite modulators, incretins, intestinal adaptations, adipose tissue, gut microbiota, bile acid circulation and composition, and psychosocial and behavioral changes on surgery-induced metabolic improvements and sustained type II diabetes remission. Clinical considerations, such as the surgical risks and improved indicators for bariatric surgery were also explored to contextualize the physiological mechanisms under study. The “hind gut hypothesis” emerged as an important overarching mechanism potentially responsible for many of the observed improvements. The more rapid delivery of food to the distal intestine, as well as the delayed mixing of pancreatic, gastric and bile secretions with food, likely contributes to increased nutrient-stimulation of enteroendocrine cells and greater binding of bile acids with their receptors, farnesoid X receptor and TGR5. These changes in food and secretion delivery also appear to positively affect the gut microbiota to support a non-obese microbiota profile. Calorie restriction may be responsible for the early effects of bariatric surgery, including not just a reduction in fat mass but also epigenetic changes to induce β-cell proliferation and increased insulin secretion. However, long-term benefits of bariatric surgery appear to be more closely correlated to enteroendocrine changes, including the surgery-induced changes to levels of appetite modulators that, unlike pure calorie restriction, promote feelings of satiation and reduce rates of diet failure and weight regain. Fat distribution and adipocyte function are also important contributors to both the pathophysiology of obesity-related diabetes and improvements following bariatric surgery. While reductions in BMI and subcutaneous adipose tissue area were not correlated to diabetes remission, reductions in visceral adipose tissue area and enhanced adiponectin secretions were both independent factors associated with diabetes remission. The important role of adipocytes as endocrine organs has emerged as an important field of inquiry. Adipokines, adipocyte hormones, may either promote a pro-inflammatory profile or an anti-inflammatory profile, impacting the development of obesity-related diabetes or diabetes remission, respectively. The findings of this review support the 2nd Diabetes Surgical Summit’s recommendations of proactive bariatric surgery as a treatment for diabetes. The risks of complications and mortality following bariatric surgery are low, whereas the long-term survival after bariatric surgery is improved relative to non-surgical, matched controls. Single-nucleotide polymorphisms associated with obesity and diabetes may serve as early indicators for surgery, and inform both surgical method and follow-up protocols. Despite the benefits of bariatric surgery, only a small number of eligible candidates undergo treatment. In the United States, barriers such as physician and patient perceptions and cost may limit access to surgery. In places that experience a health workforce shortage, there may be no health care professionals or facilities available to perform bariatric surgery. Therefore, while the surgery amazingly causes diabetes remission, one of its greatest benefits may be to continue to inform the mechanisms responsible for metabolic improvements toward developing new pharmacological treatments. In the future, less invasive drug treatments that seek to replicate the effects of bariatric surgery may be more successful in tackling the global obesity and diabetes crisis.