Impact of GBS on CVD in Type 2 Diabetes Mellitus

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.

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:

1. Current regular use of insulin

2. Current regular use of oral hypoglycemic medication.

3. 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 12 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.