Clinical Trial: Fatty Acid Oxidation Defects and Insulin Sensitivity

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Role of Fatty Acid Oxidation Defects in Insulin Sensitivity

Brief Summary: The purpose of this study is to learn more about what causes insulin resistance. It has been suggested that proper breakdown of fat into energy (oxidation) in the body is important to allow insulin to keep blood sugar in the normal range. The investigators want to know if having one of the fatty acid oxidation disorders could have an influence on insulin action. Fatty acid oxidation disorders are genetic disorders that inhibit one of the enzymes that converts fat into energy. The investigators will study both normal healthy people and people with a long-chain fatty acid oxidation disorder.

Detailed Summary:

The overall goal of this proposal is to investigate the effects of disordered mitochondrial fatty acid oxidation on insulin resistance in humans. Mitochondrial dysfunction has been implicated in the development of insulin resistance and type 2 diabetes during excess dietary fat intake and from increased release of endogenous free fatty acids , such as occurs in obesity. Controversy exists, however, as to whether this insulin resistance results from intrinsic defects in mitochondrial energy utilization or from abnormalities resulting from excess free fatty acid flux, as well as the role that subsequent accumulation of cellular metabolic intermediates play in impaired insulin signaling.

To address these controversies, the investigators will study a unique population of patients with inherited defects in each of the three mitochondrial enzymes in the fatty acid oxidation pathway: 1) very long-chain acyl-CoA dehydrogenase (VLCAD); 2) trifunctional protein (TFP, which includes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD)); and 3) medium-chain acyl-CoA dehydrogenase (MCAD). These proteins are required for the oxidation of sequentially shorter fatty acids . The investigators will test the hypothesis that intrinsic defects in mitochondrial function involving oxidation of long-chain, but not medium-chain, fatty acids are sufficient to prevent intralipid-induced insulin resistance.


Sponsor: Oregon Health and Science University

Current Primary Outcome: Glucose Disposal Rate (Rd)- the rate of glucose infusion to maintain euglycemia during steady state insulin infusion in ml/kg/hr [ Time Frame: 5 hours ]

Amount of glucose disposal during hyperinsulinemic euglycemic clamp


Original Primary Outcome: Same as current

Current Secondary Outcome: Endogenous glucose production (Ra) - calculated by the equations of Steele during steady state in ml/kg/hr [ Time Frame: 5 hours ]

Amount of glucose endogenously synthesized and secreted into circulation


Original Secondary Outcome: Same as current

Information By: Oregon Health and Science University

Dates:
Date Received: July 2, 2015
Date Started: February 2016
Date Completion: April 2019
Last Updated: September 26, 2016
Last Verified: September 2016