Long-term effects of a sustained-release preparation of acipimox on dyslipidemia and glucose metabolism in non-insulin-dependent diabetes mellitus.
Elevated circulating plasma nonesterified fatty acids (NEFA) may contribute to the insulin resistance and hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM), and decreasing plasma NEFA could provide a therapeutic benefit. A sustained-release preparation of acipimox, a lipolysis inhibitor, was used in an attempt to decrease circulating plasma NEFA levels long-term, and the effects on glycemic control, insulin resistance, and serum lipids were measured. Sixty NIDDM patients (43 males and 17 females) took part in a randomized controlled trial of acipimox or placebo for 12 weeks. Fasting plasma NEFA levels did not change in acipimox-treated patients (baseline v 12 weeks, 0.84 +/- 0.35 v 0.88 +/- 0.55 mmol x L(-1), mean +/- SD). Fasting blood glucose was unchanged (mean difference v placebo, -0.5 mmol x L(-1); 95% confidence interval [CI], -1.4 to 0.3 mmol x L[-1]), but serum fructosamine decreased (mean difference v placebo, -26 micromol x L(-1); 95% CI, -51 to 0 mmol x L[-1]), as did the standardized hemoglobin A1 ([HbA1] mean difference v placebo, -1.4%; 95% CI, -3.0% to -0.1%). Insulin resistance measured as steady-state plasma glucose during an insulin-dextrose infusion test was unchanged (mean difference v placebo, -1.4 mmol x L(-1); 95% CI, -3.2 to 0.5 mmol x L[-1]). Serum total cholesterol (mean difference v placebo, -0.4 mmol x L(-1); 95% CI, -0.6 to -0.1 mmol x L[-1]), serum apolipoprotein B ([apo B] mean difference v placebo, -0.19 g x L(-1); 95% CI, -0.3 to -0.1 g x L[-1]), and serum triglycerides (mean difference v placebo for pretreatment v posttreatment ratio, 0.59; 95% CI, 0.40 to 0.88) were all lower with acipimox. Serum high-density lipoprotein (HDL) cholesterol (mean difference v placebo, 0.10 mmol x L(-1); 95% CI, -0.05 to 0.3 mmol x L[-1]), serum apo A1 (mean difference v placebo, 0.03 g x L(-1); 95% CI, -0.04 to 0.1 g x L[-1]), and serum lipoprotein(a) ([Lp(a)] acipimox v placebo, 154 (0 to 1,574) v 71 (0 to 1,009), median and range) were unchanged. Despite the lack of change in fasting plasma NEFA levels, acipimox caused a modest beneficial improvement in overall glycemic control and plasma lipids in NIDDM patients and could be a useful agent in the treatment of dyslipidemic NIDDM patients.
Davoren
P M
PM
Human Diabetes and Metabolism Research Centre, University of Newcastle upon Tyne, UK.
Kelly
W
W
Gries
F A
FA
Hubinger
A
A
Whately-Smith
C
C
Alberti
K G
KG
D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D010919:Placebos; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001786:Blood Glucose; D003692:Delayed-Action Preparations; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D010919:Placebos; D011719:Pyrazines; D014280:Triglycerides; D002784:Cholesterol; C027696:acipimox