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J Clin Endocrinol Metab. 2010 Mar;95(3):1256-64. doi: 10.1210/jc.2009-1932. Epub 2010 Jan 22.

Plasma nonesterified Fatty Acid intolerance and hyperglycemia are associated with intravenous lipid-induced impairment of insulin sensitivity and disposition index.

Author information

1
Division of Endocrinology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Qu├ębec, Canada J1H 5N4. andre.carpentier@usherbrooke.ca

Abstract

CONTEXT:

It is currently unclear why susceptibility to lipid-induced impairment of beta-cell function varies in different populations.

OBJECTIVE:

The aim of the study was to determine whether mild hyperglycemia may be associated with nonesterified fatty acid (NEFA) intolerance and increased iv lipid-induced lipotoxic effect on the beta-cell.

DESIGN AND SETTING:

The study consisted of an experimental design with control group conducted at an academic clinical research center.

PARTICIPANTS:

Twenty-six overweight or obese individuals (12 with normal glucose tolerance, nine with impaired glucose tolerance or type 2 diabetes, and five subjects who previously had impaired glucose tolerance or type 2 diabetes but at the time of study had normal glucose tolerance after biliopancreatic diversion).

INTERVENTIONS:

We assessed insulin sensitivity (S(I)) and beta-cell function [insulin disposition index (DI)] after an overnight iv infusion of heparin + Intralipid (HI) vs. normal saline for 16 h using a stepwise, incremental iv glucose infusion followed by a hyperglycemic clamp.

MAIN OUTCOME MEASURES:

We measured S(I), DI, HI-induced change in plasma NEFA, and its association with HI-induced change in S(I) and DI.

RESULTS:

HI resulted in significant reduction in S(I) and DI across the three groups of participants. HI-induced elevation of plasma NEFA was higher in hyperglycemic vs. normoglycemic groups. Both fasting glucose level and the magnitude of HI-induced NEFA elevation were associated with the reduction in S(I) (P = 0.007 and P = 0.01, respectively) and DI (P = 0.001 and P = 0.007, respectively).

CONCLUSION:

Mild hyperglycemia and NEFA intolerance to iv lipid are associated with susceptibility to lipid-induced reduction in S(I) and DI.

PMID:
20097711
DOI:
10.1210/jc.2009-1932
[Indexed for MEDLINE]

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