Type 2 Diabetes: Etiology and Reversibility

Roy Taylor, MD, FRCP

Disclosures

Diabetes Care. 2013;36(4):1047-1055. 

In This Article

Reversal of Type 2 Diabetes by Bariatric Surgery

The first hint that type 2 diabetes is a fully reversible syndrome came from bariatric surgery. Almost a quarter century ago, Pories et al.[12] demonstrated that blood glucose levels normalized in obese people with type 2 diabetes undergoing bariatric surgery and that 10 years later, almost 90% remained free of diabetes. The phenomenon was more recently tested in a randomized prospective study comparing gastric banding with intensive medical therapy for type 2 diabetes.[13] This least invasive type of surgery was most suitable for the randomized study, although it was associated with lower rates of diabetes reversal than other procedures. Mean fasting plasma glucose fell to normal levels in the surgically treated group but declined only modestly in the intensive medical treatment group despite oral agents and insulin (Fig. 1).[13] Remission of diabetes was related to the degree of weight loss rather than to group allocation and was achieved in 73% of the surgical group and 13% of the intensive medical treatment group because surgery was more effective in achieving weight loss as previously described.[14] Type 2 diabetes can be reversed by applying a surgical procedure that diminishes fat mass.

Figure 1.

A: Fasting plasma glucose and weight change 2 years after randomization either to gastric banding or to intensive medical therapy for weight loss and glucose control. Data plotted with permission from Dixon et al.13 B: Early changes in fasting plasma glucose level following pancreatoduodenal bypass surgery. A decrease into the normal range was seen within 7 days. Reproduced with permission from Taylor.98

However, the observation that normalization of glucose in type 2 diabetes occurred within days after bariatric surgery, before substantial weight loss,[15] led to the widespread belief that surgery itself brought about specific changes mediated through incretin hormone secretion.[16,17] This reasoning overlooked the major change that follows bariatric surgery: an acute, profound decrease in calorie intake. Typically, those undergoing bariatric surgery have a mean body weight of ~150 kg[15] and would therefore require a daily calorie intake of ~13.4 MJ/day (3,200 kcal/day) for weight maintenance.[18] This intake decreases precipitously at the time of surgery. The sudden reversal of traffic into fat stores brings about a profound change in intracellular concentration of fat metabolites. It is known that under hypocaloric conditions, fat is mobilized first from the liver and other ectopic sites rather than from visceral or subcutaneous fat stores.[19] This process has been studied in detail during more moderate calorie restriction in type 2 diabetes over 8 weeks.[20] Fasting plasma glucose was shown to be improved because of an 81% decrease in liver fat content and normalization of hepatic insulin sensitivity with no change in the insulin resistance of muscle.

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