Ciprofibrate effects on carbohydrate and lipid metabolism in type 2 diabetes mellitus subjects.
OBJECTIVE
Atherosclerosis is the most common cause of morbidity and mortality in type 2 diabetes mellitus. Hyperglycemia, dyslipoproteinemia, arterial hypertension and coagulation abnormalities are the most important cardiovascular risk factors. Hypertriglyceridemia and low high density lipoprotein-cholesterol (HDLc) seem to be related with insulin resistance. Fibric acid derivates (fibrates) are effective in the treatment of dyslipoproteinemia in diabetes. Our aim was to evaluate the efficacy and safety of ciprofibrate in improving dyslipoproteinemia and its effect on fibrinogen plasma concentrations, carbohydrate metabolism variations and insulin action.


RESULTS
13 subjects with type 2 diabetes mellitus were treated with diet and placebo for 4 weeks and then randomized to one of two treatments: ciprofibrate 100 mg or placebo for four weeks. After a four-week wash-out period they were crossed over as shown in Figure 1. Total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDLc), very low density lipoprotein-cholesterol (VLDLc), HDLc, Apolipoprotein B100, fibrinogen, insulin and Lp(a) were measured. Insulin erythrocytes union was made by the Gambhir method. There was a 15% decrease in total cholesterol (p < 0.05) and 47% decrease in triglycerides (p < 0.01); similar changes were observed in VLDL-cholesterol and VLDL-triglycerides; 17% increase in HDL-cholesterol (p < 0.05). No significant differences were observed in LDL-cholesterol, apolipoprotein B100 and lipoprotein (a). Fibrinogen decreased 10% (p < 0.05). A non-significant 10% decrease in insulin secretion (area under curve) after oral glucose was observed with ciprofibrate. These findings indicate a decrease in receptor affinity. A non-significant decrease in insulin receptor number/cells was also observed.


CONCLUSIONS
Ciprofibrate has a potent hypolipidemic effect, especially a decrease in triglycerides, VLDL and fibrinogen, and an increase in HDL-cholesterol, but does not influence glycemic control nor insulin action. Decreased insulin secretion may be due to peripheral use of glucose due to the drug's antilipolytic action.
Hernández-Mijares
A
A
Hospital Universitario Dr. Peset, Universidad de Valencia, Spain.
Lluch
I
I
Vizcarra
E
E
Martínez-Triguero
M L
ML
Ascaso
J F
JF
Carmena
R
R
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D019540:Area Under Curve; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D004311:Double-Blind Method; D005260:Female; D058607:Fibric Acids; D005340:Fibrinogen / Q000187:drug effects* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050356:Lipid Metabolism; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001786:Blood Glucose; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D002995:Clofibric Acid; D058607:Fibric Acids; D005340:Fibrinogen; D006442:Glycated Hemoglobin; D000960:Hypolipidemic Agents; D017270:Lipoprotein(a); D014280:Triglycerides; C019304:ciprofibrate