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.
AuthorsP M Davoren, W Kelly, F A Gries, A Hubinger, C Whately-Smith, K G Alberti
JournalMetabolism: clinical and experimental (Metabolism) Vol. 47 Issue 3 Pg. 250-6 (Mar 1998) ISSN: 0026-0495 [Print] UNITED STATES
PMID9500558 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Apolipoprotein A-I
  • Apolipoproteins B
  • Blood Glucose
  • Delayed-Action Preparations
  • Fatty Acids, Nonesterified
  • Hypolipidemic Agents
  • Insulin
  • Placebos
  • Pyrazines
  • Triglycerides
  • Cholesterol
  • acipimox
  • Apolipoprotein A-I (metabolism)
  • Apolipoproteins B (blood)
  • Blood Glucose (metabolism)
  • Cholesterol (blood)
  • Delayed-Action Preparations
  • Diabetes Mellitus, Type 2 (blood, complications, drug therapy)
  • Double-Blind Method
  • Fasting
  • Fatty Acids, Nonesterified (blood)
  • Female
  • Humans
  • Hyperlipidemias (complications, drug therapy)
  • Hypolipidemic Agents (administration & dosage, therapeutic use)
  • Insulin (blood)
  • Male
  • Placebos
  • Pyrazines (administration & dosage, therapeutic use)
  • Triglycerides (blood)

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