Potential of Surgery for Curing Type 2 Diabetes Mellitus

Francesco Rubino, MD, Michel Gagner, MD, FACS, FRCSC


Annals of Surgery. 2002;236(5) 

In This Article

Possible Mechanisms of Action

One might think that surgically induced weight loss and decreased food intake are the most reasonable mechanisms for remission of diabetes after surgery for obesity, but most reported series do not support this explanation.

Most reported series show that return to euglycemia and normal insulin levels occur within days after surgery, long before there is any significant weight loss.[15,24,25] In 1995, Pories et al[24] reported the results of GBP in a series of 608 morbidly obese patients. Preoperatively, 146 patients were diabetic (type 2) and 152 had impaired glucose tolerance. GBP achieved normal levels of plasma glucose, insulin, and glycosylated hemoglobin in 83% of diabetic patients and in 98.7% of patients with impaired glucose tolerance within 4 months after surgery, without the need for any diabetic medication or special diet, and before any weight reduction occurred. In 1998, Scopinaro et al[15] reported normalization of glucose levels in 100% of their morbidly obese patients after BPD with no need for medication and on a totally free diet as early as 1 month after operation, when excess weight was still more than 80%. Hickey et al[25] demonstrated significantly lower levels of fasting plasma glucose, plasma insulin, and serum leptins in a group of patients maintaining stable weight after GBP compared to a group of patients matched in weight, age, and percentage of fat who did not undergo surgery. A clinical case described in detail by Pories and Albrecht[29] is instructive. This woman with a fasting blood glucose of 495 mg/dL despite daily administration of 90 units insulin underwent GBP. On the first day after surgery her blood glucose fell to 281 mg/dL and her insulin requirement was only 8 units. By day 6 she no longer required insulin, and she subsequently remained euglycemic without insulin or other hypoglycemic agents on a regular diet for the following years.

If decreased food intake explains how the GBP and BPD procedures control diabetes, gastroplasties should be effective too, since these operations significantly lower food intake by reduction of gastric volume. Gastroplasties do indeed improve glucose metabolism,[30,31] but there is no evidence for long-term cure of diabetes in morbidly obese patients. Furthermore, vertical banded gastroplasty results in less reduction of hyperglycaemia and hyperinsulinemia than GBP does.[32] Also, patients undergoing BPD show only temporary food intake limitation; over time, their eating capacity is fully restored or even increased,[15] while blood glucose levels remain under control.

To understand what the mechanism of diabetes control might be, we should look at the anatomical and physiologic alterations that these surgeries cause. GBP and BPD differ in terms of the volume of the gastric remnant and the length of bowel exposed to the mixture of food and biliopancreatic juices. However, these procedures have in common the exclusion of duodenum and at least part of the jejunum from the transit of food. This bypass has two obvious consequences: undigested or incompletely digested food is presented early to the ileum, and the duodenum and jejunum are excluded from the enteroinsular axis. Both mechanisms suggest that the effect of GBP and BPD on diabetes is mediated by a change in the pattern of secretion of gastrointestinal hormones.

Pories et al provide one possible explanation.[29] Their hypothesis is that GBP (we would include BPD also) excludes the site responsible for the production of the hormone causing type 2 diabetes. In their model, the hyperinsulinemia in type 2 diabetes is the result of an abnormal incretin signal from the gut, while the insulin resistance is a secondary protective phenomenon.

Other explanations are possible. For example, a hormone overproduced in the proximal foregut in diabetic patients might not directly increase the production of insulin, as suggested by Pories et al, but rather counteract the action of insulin, thus inducing insulin resistance and only secondarily hyperinsulinemia. For instance, in susceptible individuals, chronic exaggerated stimulation of the proximal gut with fat and carbohydrates may induce overproduction of an unknown factor that causes impairment of incretin production and/or action, leading to insufficient or untimely production of insulin so that glucose intolerance develops (Figs. 1 and 2). In our opinion, the bypass of the duodenum and jejunum avoids this phenomenon, while the early presentation of undigested or incompletely digested food to the ileum may anticipate the production of hormones such as glucagon-like peptide 1 (GLP1), further improving insulin action (Fig. 3).

We hypothesize that the complex reaction of the endocrine bowel to meal ingestion in normal subjects includes production of both incretins (which stimulate insulin secretion and action) and other unknown factors that inhibit the effects of incretins as a sort of negative feedback mechanism.

We speculate that type 2 diabetes might be the result of an imbalance in the equilibrium between anti-incretin factors and incretins, which eventually leads to delayed insulin response and impaired insulin action (A). The anti-incretin factors are most likely overproduced in the proximal foregut of diabetics.

Hypothesis as to the mechanism responsible for the control of diabetes after gastric bypass.


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