462 Obesity Surgery, 15, 2005 © FD-Communications Inc. Obesity Surgery, 15, 462-473 The prevalence of type 2 diabetes mellitus (T2DM) and obesity in the western world is steadily increas- ing. Bariatric surgery is an effective treatment of T2DM in obese patients. The mechanism by which weight loss surgery improves glucose metabolism and insulin resistance remains controversial. In this review, we propose that two mechanisms participate in the improvement of glucose metabolism and insulin resistance observed following weight loss and bariatric surgery: caloric restriction and weight loss. Nutrients modulate insulin secretion through the entero-insular axis. Fat mass participates in glucose metabolism through the release of adipocytokines. T2DM improves after restrictive and bypass proce- dures, and combinations of restrictive and bypass procedures in morbidly obese patients. Restrictive procedures decrease caloric and nutrient intake, decreasing the stimulation of the entero-insular axis. Gastric bypass (GBP) operations may also affect the entero-insular axis by diverting nutrients away from the proximal GI tract and delivering incompletely digested nutrients to the distal GI tract. GBP and bil- iopancreatic diversion combine both restrictive and bypass mechanisms. All procedures lead to weight loss and decrease in the fat mass. Decrease in fat mass significantly affects circulating levels of adipocytokines, which favorably impact insulin resist- ance. The data reviewed here suggest that all forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. This suggests that improvements in glucose metabo- lism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake and in the long-term by decreased fat mass and resulting changes in release of adipocytokines. Observed changes in glucose metabolism and insulin resistance following bariatric surgery do not require the posit of novel regulatory mechanisms. Key words: Diabetes, insulin resistance, obesity, morbid obesity, weight loss, bariatric surgery Introduction The prevalence of obesity is steadily increasing worldwide and is associated with some of the most common diseases affecting the developed world: type 2 diabetes mellitus (T2DM), coronary artery disease, hypertension and cancer. Obesity now affects over 34 million Americans of which almost one-third are classified as morbidly obese, defined as a body mass index (BMI) ≥40 kg/m 2 . 1 Indications for surgery now include morbidly obese patients or patients with a BMI >35 with co-morbidities. 2 Although the initial impetus driving the development of bariatric opera- tions was for weight loss in the obese, another impor- tant goal of bariatric surgery has become the amelio- ration and treatment of T2DM. Obesity, Insulin Resistance and Type 2 Diabetes Mellitus In 1992, Pories drew attention to the dramatic improvement in T2DM following gastric bypass for morbid obesity. 3 This observation has been con- firmed by many others. 1,2,4,5 Vertical banded gastro- plasty (VBG) and laparoscopic adjustable gastric banding (LAGB) are restrictive operations that limit Review Changes in Insulin Resistance Following Bariatric Surgery: Role of Caloric Restriction and Weight Loss Andrew A. Gumbs, MD 1 ; Irvin M. Modlin, MD, PhD 1 ; Garth H. Ballantyne, MD 2 Departments of Surgery, 1 Yale University School of Medicine, New Haven, CT, and 2 Hackensack University Medical Center, Hackensack, NJ, USA Reprint requests to: Garth H. Ballantyne, MD, Professor of Surgery, Hackensack University Medical Center, 20 Prospect Avenue, Suite 901, Hackensack, NJ 07601, USA. Fax: 1-201- 996-3222; e-mail: ghb@lapsurgery.com