What can bariatric surgery teach us about the pathophysiology of type 2 diabetes?
Bariatric surgery is indicated in cases of severe obesity. However, malabsorption-based techniques (gastric bypass and biliopancreatic diversion, both of which exclude the duodenum and jejunum from the alimentary circuit), but not restrictive techniques, can abolish type 2 diabetes within days of surgery, even before any significant weight loss has occurred. This means that calorie restriction alone cannot entirely account for this effect. In Goto-Kakizaki rats, a type 2 diabetes model, glycaemic equilibrium is improved by surgical exclusion of the proximal intestine, but deteriorates again when the proximal intestine is reconnected to the circuit in the same animals. This effect is independent of weight, suggesting that the intestine is itself involved in the immediate regulation of carbohydrate homoeostasis. In humans, the rapid improvement in carbohydrate homoeostasis observed after bypass surgery is secondary to an increase in insulin sensitivity rather than an increase in insulin secretion, which occurs later. Several mechanisms are involved--disappearance of hypertriglyceridaemia and decrease in levels of circulating fatty acids, disappearance of the mechanisms of lipotoxicity in the liver and skeletal muscle, and increases in secretion of GLP-1 and PYY--and may be intricately linked. In the medium term and in parallel with weight loss, a decrease in fatty tissue inflammation (which is also seen with restrictive techniques) may also be involved in metabolic improvement. Other mechanisms specific to malabsorption-based techniques (due to the required exclusion of part of the intestine), such as changes in the activity of digestive vagal afferents, changes in intestinal flora and stimulation of intestinal neoglucogenesis, also need to be studied in greater detail. The intestine is, thus, a key organ in the regulation of glycaemic equilibrium and may even be involved in the pathophysiology of type 2 diabetes.
CHU Bichat Claude Bernard, AP-HP, Service de Diabétologie-Endocrinologie-Nutrition,75877 Paris cedex 18, France.
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Andreelli
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Amouyal
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Magnan
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Mithieux
D050153:Abdominal Fat; D000818:Animals; D050110:Bariatric Surgery; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D015986:Confounding Factors, Epidemiologic; D048909:Diabetes Complications / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery*; D004040:Dietary Carbohydrates / Q000378:metabolism*; D015390:Gastric Bypass; D015391:Gastroplasty; D005943:Gluconeogenesis; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance; D007581:Jejunoileal Bypass; D050356:Lipid Metabolism; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery*; D015431:Weight Loss
D001786:Blood Glucose; D004040:Dietary Carbohydrates