The effect of metformin and rosiglitazone on postprandial lipid metabolism in obese insulin-resistant subjects.
BACKGROUND
Obese insulin-resistant individuals exhibit a dyslipidaemia due to raised levels of both hepatically and intestinally derived lipoproteins. However, little is known about the related dysregulation of intestinally derived lipoproteins. We examined whether the insulin-sensitizing agents, metformin and rosiglitazone, improve intestinal lipoprotein metabolism in obese insulin-resistant individuals.


METHODS
Thirty male obese (body mass index > 26; waist circumference > 100 cm) insulin-resistant [homeostasis model assessment (HOMA) score > 2.0] subjects were randomized to either a metformin (1 g bd), rosiglitazone (4 mg bd) or control treatment group for a period of 8 weeks. Fasting and postprandial lipid metabolism was studied before and after the intervention period.


RESULTS
Metformin and rosiglitazone both significantly improved insulin sensitivity, but this was not paralleled by improvement in dyslipidaemia. With rosiglitazone relative to control there was a significant (p < 0.05) increase in the area under the apolipoprotein (apo) B48 curve following the oral fat load and a decrease in the ratio of triglyceride to apo B48 levels postprandially following rosiglitazone treatment.


CONCLUSIONS
In obese insulin-resistant subjects metformin and rosiglitazone both improve insulin sensitivity, as measured by HOMA, without improvement in lipid metabolism. Rosiglitazone may have a detrimental effect on chylomicron metabolism by an increase in postprandial apo B48 levels, and this requires further investigation.
James
A P
AP
School of Public Health, Curtin University of Technology, Perth, WA, Australia.
Watts
G F
GF
Mamo
J C L
JC
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D019518:Postprandial Period; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D008687:Metformin