Impact of GBS on CVD in Type 2 Diabetes Mellitus
Impact of GBS on CVD in Type 2 Diabetes Mellitus
This research is a NIH single site study with the aims to (1) determine whether surgically
 induced weight loss decreases the risk of CVD in morbidly obese subjects with T2DM. (2)
 elucidate the mechanisms by which surgically induced weight loss reduces over time the risk
 of CVD in morbidly obsess subjects with T2DM.

 Study'subjects will be enrolled from obese individuals with type 2 diabetes (T2DM). The study
 includes two groups, subjects undergoing gastric bypass surgery and a control group not
 undergoing weight loss surgery. A total of 60 subjects (30 in each group) will be recruited.

 Basal, 6 and 12 months assessments will include: insulin sensitivity determination,
 cardiovascular function by echo doppler, and DEXA scan.

 This study involves risk-level II procedures, however, the risks inherent to the gastric
 bypass surgery are not considered study-derived because subjects are enrolled from
 individuals that have already decided to have this surgery. We will determine protein
 expression profiles of inflammation-related adipokines in the subcutaneous and
 intra-abdominal adipose tissues of morbidly obese subjects with T2DM before and after
 surgically induced weight loss.
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:

 -  Clinical diagnosis of T2DM diabetes mellitus with HbA1c ≤ 10.0%

 -  Current regular use of insulin

 -  Current regular use of oral hypoglycemic medication.

 -  Documented diabetes by current ADA criteria (98).

 -  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

 -  Age between 18-60 years old.

 -  Ability and willingness to provide informed consent.

 -  No expectation that subject will be moving out of the area of the clinical center
 during the next 12 months.

 Exclusion criteria:

 -  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

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

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

 -  Pregnancy or planning pregnancy

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

 -  Uncontrolled hypertension

 -  Smoking