This article provides an overview of the most recent molecular and clinical outcomes of studies that investigate the effect of weight loss and calorie restriction on carbohydrate metabolism, obtained either by dieting or bariatric surgery. It will focus on aspects of carbohydrate metabolism related to insulin action. The discussion begins by describing attempts to restrain calories by shifting the macronutrient balance from carbohydrates to a higher protein and fat content. The topics covered include insulin secretion and resistance, glucose homeostasis and allostasis, changes in the secretive patterns of adipose tissue and the entero–insular axis.
Any improvement in glucose homeostasis, insulin sensitivity and secretion after a low-carbohydrate high-fat diet is still unproved. However, the restriction of dietary carbohydrate seems to reduce glycogenolysis and endogenous glucose production in type 2 diabetes mellitus, thus inducing the amelioration of plasma glucose levels, ultimately resulting in a reduction in the glycated haemoglobin concentration. The increased endogenous glucose production caused by enhanced gluconeogenesis and glycogenolysis, reduced insulin sensitivity, mainly caused by acquired defects of glucose transport and phosphorylation, and the impairment of insulin secretion all together contribute to maintain a chronic status of hyperglycaemia. Weight loss and calorie restriction restore glucose homeostasis and produce changes in the secretive activities of adipose tissue and the entero–insular axis.
Weight loss and calorie restriction partly explain the positive changes of glucose disposal. The multistep interaction of several factors at sites of insulin action, insulin secretion, adipose tissue and the entero–insular axis needs further investigation.
Department of Internal Medicine and Clinical Science, Catholic University, Rome, Italy
Correspondence to Melania Manco, MD PhD, Department of Internal Medicine and Clinical Science, Catholic University, Largo Agostino Gemelli 8, 00168 Rome, Italy Tel: +39 6 3015 4395; fax: +39 6 3054 392; e-mail: firstname.lastname@example.org