Effects of pioglitazone in familial combined hyperlipidaemia.
OBJECTIVE
Familial combined hyperlipidaemia (FCH) is associated with insulin resistance. We hypothesized that pioglitazone treatment of FCH patients might increase insulin sensitivity, but may also improve serum lipid levels, body fat distribution, intramyocellular lipids (IMCL) and endothelial function.


METHODS
Double blind, randomized, cross-over study.


METHODS
Seventeen FCH patients.


METHODS
Sixteen weeks of pioglitazone treatment (30 mg) compared with 16 weeks of placebo.


METHODS
Insulin sensitivity was measured using the hyperinsulinaemic euglycaemic clamp procedure, body fat distribution and IMCL using magnetic resonance techniques and endothelial function using flow-mediated vasodilatation.


RESULTS
Pioglitazone improved insulin sensitivity (M value 37.7 +/- 3.6 micromol min(-1) kg(-1) vs. 33.0 +/- 3.3 micromol min(-1) kg(-1) during placebo, P < 0.05) and LDL composition by increasing the K value (-0.11 +/- 0.06 vs. -0.20 +/- 0.06 during placebo, P < 0.05). However, pioglitazone did not affect other serum lipid levels. Endothelial function, body fat distribution and IMCL were also not affected. In addition, pioglitazone was associated with a decrease in liver enzymes (alkaline phosphatase).


CONCLUSIONS
Pioglitazone treatment of FCH patients without type 2 diabetes mellitus increases insulin sensitivity, decreases liver enzymes and improves LDL composition but has a neutral effect on total serum lipid levels. The change in insulin sensitivity might be too small to induce changes in endothelial function, body fat distribution and IMCL.
Abbink
E J
EJ
Division of General Internal Medicine, Department of Medicine, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
De Graaf
J
J
De Haan
J H
JH
Heerschap
A
A
Stalenhoef
A F
AF
Tack
C J
CJ
D000410:Alanine Transaminase / Q000097:blood; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D007004:Hypoglycemic Agents; D008055:Lipids; D045162:Thiazolidinediones; D002784:Cholesterol; D000410:Alanine Transaminase; D000077205:Pioglitazone