Does Class of Dietary Fat Affect Insulin Resistance?

• Change in Insulin Sensitivity from Baseline at Two Weeks [ Time Frame: Average of 2 weeks. ] [ Designated as safety issue: No ]
  Insulin sensitivity will be measured twice (once at baseline following a nasoduodenal infusion of saline for 6 hours; two weeks later following a nasoduodenal infusion of a vegetable oil high in one of 3 fatty acids for 6 hours) using a euglycemic, hyperinsulinemic clamp as described by R. DeFronzo. The actual measurement is expressed as a glucose infusion rate.
  
  

• Change in Endothelial Function from Baseline at Two Weeks [ Time Frame: Average of two weeks ] [ Designated as safety issue: No ]
  Endothelial function will be measured by measuring the dilation of the brachial artery in the elbow following occlusion by a blood pressure cuff, which is then released. The actual measurement involves use of ultrasound by an investigator experienced with this technique.
  
  
• Change in Systolic Blood Pressure at Two Weeks [ Time Frame: Average of two weeks ] [ Designated as safety issue: No ]
  Blood pressure will be measured using a standard automated blood pressure cuff. The measurements will be taken several times during each study day.
  
  

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.