Obesity, Weight Loss, and Cardiovascular Disease Risk
| Status: | Recruiting |
|---|---|
| Conditions: | Obesity Weight Loss, Peripheral Vascular Disease |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Endocrinology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 2/4/2013 |
GCRC-CAP-Tracey McLaughlin, MD
The goal of the study is to define the roles played by resistance to insulin-mediated
glucose disposal (insulin resistance) and circulating plasma insulin concentrations in: 1)
ability to lose weight; 2) reduction of risk for coronary heart disease as a result of
weight loss. We hypothesize that in the setting of caloric restriction, manipulating
endogenous insulin concentrations will not alter ability of subjects to lose weight, but
will lead to different reduction in CHD risk factors. To test this hypothesis, two parallel
studs will be performed. First, obese insulin-resistant individuals will be randomized to
one of two equally-hypocaloric diets that vary moderately in proportion of carbohydrate and
mono/polyunsaturated fats (lower carbohydrate diet will be associated with greater reduction
in endogenous insulin secretion). Second, diabetics treated with insulin secretagogues will
be compared to diabetics treated with insulin sensitizers with respect to the same outcomes
(secretagogues increase insulin secretion and insulin sensitizers decrease insulin
concentrations). Endpoints include weight loss, change in insulin resistance, blood
pressure, lipid and lipoproteins, markers of endothelial function, daylong insulin and
glucose concentrations: these will be compared, in each of the parallel studies, between the
group with insulin-stimulating intervention vs the group with the insulin-sparing
intervention.
While obesity, insulin resistance, and diabetes are highly associated, it is not clear
whether insulin resistance and compensatory hyperinsulinemia play important roles in the
tendency to gain weight and/or inability to lose weight. The role of hyperinsulinemia in
coronary heart disease (CHD)is also unclear. The specific aims of the proposed research are
as follows:
1. To compare insulin resistant versus insulin sensitive nondiabetic overweight
individuals with respect to their ability to lose weight on a low calorie diet. CHD
risk factors before and after weight loss will also be assessed to determine the degree
to which insulin resistance is associated with CHD risk, as well as the impact that
differences in insulin resistance have on the metabolic benefits of weight loss
2. To determine if weight loss and its associated metabolic benefits vary as a function of
the relative amounts of dietary fat and carbohydrate in hypocaloric diets. Because
high carbohydrate diets increase insulin secretion, the relationship between dietary
composition and change in circulating insulin concentrations will be analyzed with
respect to both weight loss and CHD risk factors.
3. To quantify and compare the improvement in glycemic control and CHD risk factors
associated with weight loss in obese type 2 diabetics, while being treated with 1) an
insulin secretagogue (sulfonylurea) or 2) an insulin sensitizer (thiazolidinedione).
Manipulation of plasma insulin concentrations with these medications will provide a
mechanism by which to evaluate the impact of circulating insulin concentrations on the
described outcome measures.
Inclusion Criteria:- BMI 30-35
- age 35-65
- nondiabetic by fasting plasma glucose concentration
- no active major organ diseases
- insulin resistant Exclusion Criteria:- anemia
- pregnant
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Stanford University School of Medicine Vast in both its physical scale and its impact on...
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