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

Current Theories About the Pathogenesis of Type 2 Diabetes

The most recent theories portray type 2 diabetes mellitus as a heterogeneous disorder. In addition to insulin resistance, clinical studies in humans and animal data have documented a variety of defects in -cell function,[41] and most researchers agree that both insulin secretion impairment and insulin resistance contribute to the fully established disease.[42] GBP and BPD restore insulin sensitivity, but the possibility of an additional incretin-mediated effect on insulin secretion cannot be ruled out.

Though insulin is the chief acute physiologic stimulus of glucose disposal, other stimuli can also activate glucose uptake and control glycemia.[43] In vivo administration of IGF1 has a potent hypoglycemic effect and has been proven to effectively lower blood glucose concentrations in subjects with type 1 or type 2 diabetes.[44,45] Decreased levels of IGF-1 have also been documented in patients with type 2 diabetes mellitus.[46] Poulos at al[35] demonstrated that GBP significantly increases IGF-1 levels only in morbidly obese patients with diabetes and not in nondiabetic subjects.

Recent data indicate that leptin may directly affect glucose and fat metabolism.[47] Administration of leptin to normal, genetically obese, or diabetic rodents improved sensitivity to insulin and reduced hyperinsulinemia before any changes in food intake or body weight occurred.[48,49] Leptin-induced increase in fatty acid oxidation could also improve glucose uptake[50] and influence insulin sensitivity indirectly through the brain and sympathetic nervous system[49,51] or by changes in the concentration of serum fatty acids and glucose flux in the liver.[51] In the light of these effects, it is of extreme interest that leptin levels decrease rapidly after GBP and BPD without correlation with postoperative BMI.[25,36] This observation suggests that body fat composition is not the only factor that regulates leptin levels. It might be speculated that an unknown factor, produced in the duodenum or jejunum in response to food stimulation, is responsible for a sort of "leptin resistance" and compensatory increased plasma levels of leptins, which is a common finding in obese patients.[47] Accordingly, when the duodenum and jejunum are bypassed, as after GBP and BPD, the cause of leptin resistance is abolished or greatly reduced, leptin resistance is resolved, and plasma leptin levels decrease. The effect of GBP and BPD on leptin may therefore in part explain their efficacy in treatment of both obesity and diabetes.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: