Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with type 2 diabetes and hypertriglyceridaemia.
OBJECTIVE
To examine whether lowering of plasma triglyceride concentrations using the fibrate peroxisome proliferator-activated receptor (PPAR)alpha agonist gemfibrozil would influence insulin sensitivity to various aspects of intermediary metabolism among subjects with type 2 diabetes mellitus.


METHODS
A randomized placebo-controlled double-blind study in 12 subjects with type 2 diabetes were treated for 12 weeks after a 12-week dietary run-in. Insulin sensitivity was assessed using a low-dose incremental intravenous insulin infusion.


RESULTS
Gemfibrozil significantly reduced fasting serum triglyceride concentrations (p < 0.001) but had no effect on measures of diabetic control. Neither gemfibrozil nor placebo treatment altered insulin sensitivity of glucose or glycerol metabolism during low-dose insulin infusion, but significant falls in both non-esterified fatty acid (NEFA) (p = 0.003) and ketone concentrations (p = 0.002) were observed after treatment with gemfibrozil.


CONCLUSIONS
Gemfibrozil does not affect insulin sensitivity to glucose or fat metabolism in type 2 diabetes but enhances the lowering of plasma NEFA concentrations by insulin, probably by reducing hepatic fatty acid synthesis.
Whitelaw
D C
DC
Diabetes Resource Centre and Department of Clinical Biochemistry, University Hospitals Birmingham, UK. donald.whitelaw@bradfordhospitals.nhs.uk
Smith
J M
JM
Nattrass
M
M
D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D003927:Diet, Diabetic; D004311:Double-Blind Method; D005260:Female; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D010919:Placebos; D014280:Triglycerides; D002784:Cholesterol; D015248:Gemfibrozil