Does Class of Dietary Fat Affect Insulin Resistance?

Type 2 Diabetes and cardiovascular disease are closely linked. A common abnormality in both
conditions is insulin resistance. The primary cause of insulin resistance in not known. A
significant question is what dietary components contribute to the development of insulin
resistance. Based on epidemiologic data, it seems that the type of dietary fat is a
significant contributor to the development of insulin resistance. However, some researchers
argue that the main determinant is total amount of fat, not the composition.

This study is intended to determine if the main types of fat (saturated, monounsaturated and
polyunsaturated) ingested over a short time can cause insulin resistance in lean, healthy
people. It has been demonstrated that 6 hours of intravenous fat infused into lean, healthy
subjects can result in insulin resistance, as well as blood pressure elevation and
endothelial dysfunction. Whether this is so with oral fat is not known. The question is
important because there is debate about whether the type of fat is as important as the
quantity of fat in a person's daily diet. Settling this debate will enhance the ability of
health care personnel to determine the optimal dietary recommendations.

This study will make use of a high fat diet consisting of vegetable oils high in the 3 main
fatty acids in plasma (palmitate, oleate and linoleate). Because large fat loads can cause
intestinal discomfort, a feeding tube will be used to bypass the stomach. The 3 oils will be
assigned randomly following a base line study with saline 2 weeks prior to the intervention.
Our primary endpoint is insulin resistance, which will be measured by a euglycemic,
hyperinsulinemic clamp. Secondary measures will include changes in blood pressure and in
vascular reactivity as measured by ultrasound after brief occlusion of a forearm vessel. The
changes will be compared to baseline and to the other 2 groups.

Inclusion Criteria:

- Lean,healthy adults 18 - 40

- No chronic medications (birth control pills allowed)

- Weight stable

- Normal fasting labs performed at screening

- Body mass index ≤ 25 kg/M^2 .

Exclusion Criteria:

- Insulin dependent diabetes

- Thyroid disease

- History of diabetes or heart disease

- History of type 2 diabetes in parent or sibling