Impact of Gastric Bypass Surgery on Risk of CVD in Type 2 Diabetes Mellitus
Impact of Gastric Bypass Surgery on Risk of CVD in Type 2 Diabetes Mellitus
Central hypothesis is: Gastric bypass surgery reduces the risk of CVD in morbidly obese
 subjects (defined as BMI ≥35 kg/m2) with T2DM.

 To determine whether surgically induced weight loss decreases the risk of CVD in morbidly
 obese subjects with T2DM. I hypothesize that 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.
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 overweight 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 weight loss. Morbidly obese patients with body mass index (BMI) over 35 kg/m2 have
 significant difficulty 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 obese subjects with T2DM. The proposed
 study is a prospective cohort clinical 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 studies will provide the foundation for a new clinical strategy
 aimed to prevent the development of CVD in obese patients with T2DM. Furthermore, they will
 serve as the baseline for future large scale longitudinal studies based on aggregate
 occurrence of severe cardiovascular events.
Inclusion Criteria:

 1. Clinical diagnosis of T2DM diabetes mellitus with HbA1c ≤ 10.0%

 Any one of the following will be considered to be sufficient evidence that diabetes is
 present:

 -  Current regular use of insulin

 -  Current regular use of oral hypoglycemic medication.

 -  Documented diabetes by current ADA criteria (98).

 2. Body mass index ≥ 35 kg/m2 in accord with the 1991 NIH obesity surgery consensus
 conference criteria and stable weight for the previous 3 months (99).

 3. Age between 18-60 years old. Individuals older than 60 years of age are excluded due
 to their increased risk of mortality and peri-operative morbidity.

 4. Ability and willingness to provide informed consent.

 5. No expectation that subject will be moving out of the area of the clinical center
 during the next 24 months.

 Exclusion Criteria:

 1. Presence of CVD defined as: CAD, electrocardiographic criteria for past myocardial
 infarction(s), ischemic stroke, peripheral artery bypass surgery, percutaneous
 transluminal angioplasty, or amputation because of atherosclerotic disease.

 2. Significant non-diabetic co-morbidity affecting life expectancy (e.g., malignancy).

 3. Significant other co-morbidities (e.g. psychiatric disorder) that results in
 ineligibility for gastric bypass surgery.

 4. Pregnancy or planning pregnancy.

 5. Severe dyslipidemia (triglycerides >600 mg/dl or cholesterol >350 mg/dl).

 6. Uncontrolled hypertension.

 7. Smoking.