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


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


METHODS
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).


METHODS
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.


METHODS
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).


CONCLUSIONS
Mild hyperglycemia and NEFA intolerance to iv lipid are associated with susceptibility to lipid-induced reduction in S(I) and DI.
Carpentier
André C
AC
Division of Endocrinology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4. andre.carpentier@usherbrooke.ca
Bourbonnais
Annie
A
Frisch
Frédérique
F
Giacca
Adria
A
Lewis
Gary F
GF
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism*; D012044:Regression Analysis
D001786:Blood Glucose; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D006493:Heparin