Impact of GBS on CVD in Type 2 Diabetes Mellitus

• To determine whether surgically induced weight loss decreases the risk of CVD in morbidly obese subjects with Type 2 Diabetes Mellitus (T2DM) [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: No ]
  Patients with T2DM who undergo gastric bypass surgery will significantly reduce mean levels of risk factors for CVD compared with diabetic individuals with the same BMI who maintain their weight.
  
  

• To elucidate the mechanisms by which surgically induced weight loss reduces over time the risk of CVD in morbidly obese subjects with T2DM. [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: No ]
  The reduction in CVD risk is mediated by changes in the expression and release of inflammatory-related adipokines by the adipose tissue.
  
  

Patients with type 2 diabetes mellitus (T2DM) are more likely to die from cardiovascular diseases (CVD) than people without diabetes. Furthermore, Patients with diabetes have not benefited from the advances in the management of CVD and/or its risk factors that have resulted in a decrease in mortality for CVD patients without diabetes. Short-term studies have demonstrated that weight loss in over weight or obese subjects with T2DM is associated with decreased insulin resistance, substantial improvements in glycemic and lipoprotein profile, and reduction in blood pressure. However, Long-term data substantiating that these improvements can be maintained are limited. Obesity, and susceptibility to weight gain, is a chronic condition. Continuous care is required to avoid weight regain especially after intensive weigh loss. Morbidly obese patients with body mass index (BMI) over 35 kg/m2 have significant difficulties maintaining weight loss adequate to resolve obesity-related medical conditions by changes in lifestyle or pharmacologic strategies. Currently, surgical treatment of morbid obesity, termed bariatric surgery, appears to be the only modality that results in significant and sustained weight loss along with reversal of diabetes and improvements in cholesterol biosynthesis, and lipoprotein metabolism in morbidly obese patients. Given these observations, we question if patients with T2DM who undergo gastric bypass surgery will significantly reduce levels of abnormalities in vascular structure and function that are central to the development of atherosclerosis. In specific aim 1, we will determine whether surgically induced weight loss decreases the risk of CVD in morbidly obese subjects with T2DM. . In specific aim 2, we will elucidate the mechanisms by which surgically induced weight loss reduces over time the risk of CVD in morbidly obsess subjects with T2DM. The proposed study is a prospective cohort clinic trial aimed to evaluate changes over time in cardiovascular structure and function of morbidly obese subjects with T2DM undergoing gastric bypass surgery compared to a matched control group who do not undergo gastric bypass surgery. The results of the proposed study will provide the foundation for a new clinic strategy aimed to prevent the development of CVD in obese patients with T2DM. Furthermore, it will serve as the baseline for future large scale longitudinal studies based on aggregate occurrence of severe cardiovascular events.