acipimox and Hyperlipidemias

Topics: Humans; Hyperlipidemias; Hypolipidemic Agents; Pyrazines

To investigate the effect of a sustained (7-day) decrease in plasma free fatty acid (FFA) concentrations on insulin action and intramyocellular long-chain fatty acyl-CoAs (LCFA-CoAs), we studied the effect of acipimox, a potent inhibitor of lipolysis, in seven type 2 diabetic patients (age 53 +/- 3 years, BMI 30.2 +/- 2.0 kg/m2, fasting plasma glucose 8.5 +/- 0.8 mmol/l, HbA 1c 7.5 +/- 0.4%). Subjects received an oral glucose tolerance test (OGTT) and 120-min euglycemic insulin (80 mU/m2 per min) clamp with 3-[3H]glucose/vastus lateralis muscle biopsies to quantitate rates of insulin-mediated whole-body glucose disposal (Rd) and intramyocellular LCFA-CoAs before and after acipimox (250 mg every 6 h for 7 days). Acipimox significantly reduced fasting plasma FFAs (from 563 +/- 74 to 230 +/- 33 micromol/l; P < 0.01) and mean plasma FFAs during the OGTT (from 409 +/- 44 to 184 +/- 22 micromol/l; P < 0.01). After acipimox, decreases were seen in fasting plasma insulin (from 78 +/- 18 to 42 +/- 6 pmol/l; P < 0.05), fasting plasma glucose (from 8.5 +/- 0.8 to 7.0 +/- 0.5 mmol/l; P < 0.02), and mean plasma glucose during the OGTT (from 14.5 +/- 0.8 to 13.0 +/- 0.8 mmol/l; P < 0.05). After acipimox, insulin-stimulated Rd increased from 3.3 +/- 0.4 to 4.4 +/- 0.4 mg x kg(-1) x min(-1) (P < 0.03), whereas suppression of endogenous glucose production (EGP) was similar and virtually complete during both insulin clamp studies (0.16 +/- 0.10 vs. 0.14 +/- 0.10 mg x kg(-1) x min(-1); P > 0.05). Basal EGP did not change after acipimox (1.9 +/- 0.2 vs. 1.9 +/- 0.2 mg x kg(-1) x min(-1)). Total muscle LCFA-CoA content decreased after acipimox treatment (from 7.26 +/- 0.58 to 5.64 +/- 0.79 nmol/g; P < 0.05). Decreases were also seen in muscle palmityl CoA (16:0; from 1.06 +/- 0.10 to 0.75 +/- 0.11 nmol/g; P < 0.05), palmitoleate CoA (16:1; from 0.48 +/- 0.05 to 0.33 +/- 0.05 nmol/g; P = 0.07), oleate CoA (18:1; from 2.60 +/- 0.11 to 1.95 +/- 0.31 nmol/g; P < 0.05), linoleate CoA (18:2; from 1.81 +/- 0.26 to 1.38 +/- 0.18 nmol/g; P = 0.13), and linolenate CoA (18:3; from 0.27 +/- 0.03 to 0.19 +/- 0.02 nmol/g; P < 0.03) levels after acipimox treatment. Muscle stearate CoA (18:0) did not decrease after acipimox treatment. The increase in R(d) correlated strongly with the decrease in muscle palmityl CoA (r = 0.75, P < 0.05), oleate CoA (r = 0.76, P < 0.05), and total muscle LCFA-CoA (r = 0.74, P < 0.05) levels. Plasma adiponectin did not change significantly after acipimox treatm

Topics: Acyl Coenzyme A; Adiponectin; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Hyperlipidemias; Hypolipidemic Agents; Insulin; Male; Middle Aged; Muscle, Skeletal; Pyrazines

32 patients with hypertriglyceridemia, excessive hypertriglyceridemia, and combined hyperlipidemia, were treated with the nicotinic acid derivative acipimox (Olbetam). First line treatment with bezafibrate, or statins in some with combined hyperlipidemia, had failed. In 10 acipimox was discontinued due to side effects or absence of clinical response. The other 22 completed 6 months of treatment with no side effects. Acipimox caused a significant 54% decrease in triglyceride levels, a 23% decrease in total cholesterol, and a 12% increase in HDL-cholesterol. LDL-cholesterol was difficult to calculate because of the high triglyceride levels, so no results are presented. Although acipimox was much better tolerated than nicotinic acid, it also had side effects, but fewer. Acipimox can therefore be used as a second-line drug, mainly in those with combined hyperlipidemia and hypertriglyceridemia.

Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Drug Therapy, Combination; Female; Humans; Hyperlipidemias; Hypertriglyceridemia; Hypolipidemic Agents; Male; Middle Aged; Pyrazines; Triglycerides

To assess the feasibility of an intensive lipid-lowering strategy in diabetic subjects pursuing target plasma lipid levels.. Patients with diabetes mellitus (DM), Type 1 or 2, with plasma lipid levels exceeding target values (LDL-cholesterol <2.6 mmol/l, triglycerides < 1.7 mmol/l, HDL-cholesterol > 0.9 mmol/l for men and > 1.1 mmol/l for women) were eligible. After 6-12 weeks of diet and glycaemic control, lipid-lowering medication (simvastatin/gemfibrozil/acipimox) was prescribed in steps of incremental dosages and combinations for 30 weeks.. Of all eligible clinic patients, 25% initially responded and finally 12% were entered. Thirty-six patients with Type 1 and 59 with Type 2 DM were studied. Mean baseline lipid levels in Type 1 and Type 2 diabetic subjects were: LDL-cholesterol 3.6 and 3.7 mmol/l, triglycerides 1.7 and 2.2 mmol/l, HDL-cholesterol for men 1.1 and 1.0 mmol/l, and for women 1.4 and 1.2 mmol/l, respectively. All three target values were reached in 66% of the patients. LDL-cholesterol was reduced by 1.2 mmol/l in Type 1 and 1.3 mmol/l in Type 2 diabetic patients and triglycerides by 0.7 mmol/l and 1.1 mmol/l, respectively. HDL-cholesterol increased by 0.15 mmol/l and 0.34 mmol/l in men and women with Type 1 diabetes mellitus, respectively. The cholesterol-triglyceride ratio decreased significantly in VLDL in Type 1 diabetes and in IDL in Type 2 diabetes and increased significantly in HDL in Type 2 DM.. A minority of subjects eligible for intensive lipid lowering agreed to participate in a feasibility study, suggesting a potentially large compliance problem for a general lipid-lowering programme in a diabetes clinic. Nevertheless, intensive lipid lowering with drug combinations can attain the recommended target lipid levels in 66% of subjects with diabetes. With this strategy the plasma lipoprotein composition shifts towards a less atherogenic profile. Subjects with diabetes should therefore receive lipid-lowering therapy tailored to reach target levels, rather than standard dosages, in order to reduce atherogenic risk.

Topics: Adult; Aged; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet; Female; Gemfibrozil; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins; Male; Middle Aged; Pyrazines; Simvastatin; Triglycerides

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.

Topics: Apolipoprotein A-I; Apolipoproteins B; Blood Glucose; Cholesterol; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Fatty Acids, Nonesterified; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Insulin; Male; Placebos; Pyrazines; Triglycerides

Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a nicotinic acid like lipid lowering drug with less side-effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia.. Randomized double-blind placebo controlled crossover trial.. Outpatient lipid clinic of a tertiary referral centre.. Eighteen patients with combined hyperlipidaemia treated with diet and 20-40 mg simvastatin for at least 3 months.. Acipimox in a daily dose of 3 X 250 mg for 12 weeks.. Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL-size and LDL-resistance to oxidative modification.. Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG > 4 mmol L- [1]), acipimox induced a significant increase in HDLc (+ 15%, P < 0.01). The effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but none of these changes reached the level of significance.. Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels. HDLc was also significantly improved.

Topics: Adult; Aged; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins; Male; Middle Aged; Pyrazines; Simvastatin; Treatment Outcome

In type 2 diabetes, it is not uncommon to find an elevated serum triglyceride and/or reduced high-density lipoprotein (HDL) cholesterol levels; elevated total cholesterol levels often occur as well. To evaluate the short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes who have mixed dyslipidemia, an open-label 6-month trial was conducted. All patients had type 2 diabetes (n = 33) with total cholesterol > or = 6.2 mmol/L and fasting triglyceride > or = 2.8 mmol/L, which had been confirmed twice and persisted for at least 12 weeks after introduction of diet control. After a 4-week run-in period, they were given lovastatin 40 mg daily at night for 12 weeks. Acipimox 250 mg three times a day was then added for a further 12 weeks. After 12 weeks of treatment with lovastatin alone, improvement was observed in total cholesterol (21% reduction), triglyceride (32% reduction), low-density lipoprotein (LDL) cholesterol (5.5% reduction), HDL cholesterol (11.6% elevation), apolipoprotein A-I (4.6% elevation), and apolipoprotein B (20.5% reduction). The addition of acipimox to lovastatin for an additional 12 weeks further reduced serum total cholesterol, triglyceride, LDL cholesterol, and apolipoprotein B, but this additional decrease was not statistically significant. However, HDL cholesterol and apolipoprotein A-I levels were significantly increased by the addition of acipimox (a 14.2% and 9.0% elevation, respectively). Serum creatine phosphokinase increased slightly after 12 weeks of lovastatin but decreased to a concentration similar to baseline after 12 weeks of combination treatment. No patients reported muscle pain or weakness or other side effects. Combination treatment with lovastatin and acipimox appears to be a safe and effective therapy in patients with type 2 diabetes and mixed dyslipidemia, and has particular benefit in elevating serum HDL cholesterol and apolipoprotein A-I levels.

Topics: Adult; Aged; Anticholesteremic Agents; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lovastatin; Male; Middle Aged; Pyrazines

Nicotinic acid, an effective drug for treatment of combined hyperlipidaemia, is often not tolerated because of side-effects. Acipimox is a nicotinic acid like lipid lowering drug with less side-effects. We studied whether the addition of acipimox to simvastatin improves the lipid profile in patients with a combined hyperlipidaemia.. Randomized double-blind placebo controlled crossover trial.. Outpatient lipid clinic of a tertiary referral centre.. Eighteen patients with combined hyperlipidaemia treated with diet and 20-40 mg simvastatin for at least 3 months.. Acipimox in a daily dose of 3 x 250 mg for 12 weeks.. Effects on the concentration of LDLc, TG, HDLc, Lp(a) and Apolipoprotein B, as well as on LDL-size and LDL-resistance to oxidative modification.. Acipimox reduced Lp(a) levels by 8% (P < 0.05). A substantial but not statistically significant change in TG (-32%) and HDLc (+6%) levels was seen. All patients were found to have small dense LDL, with a size of 229 +/- 4 A. LDL size and the resistance to oxidation, reflected in the lag phase during in vitro oxidation, were not affected by the addition of acipimox. In a subgroup of 8 patients with the most severe hypertriglyceridaemia (baseline TG < 4 mmol L- [1]), acipimox induced a significant increase in HDLc (+15%, P < 0.01). The effects on TG (-41%), LDLc (-10%) and lag phase (+17%) were also more pronounced than in the group with a lower baseline TG, but non of these changes reached the level of significance.. Adding acipimox to simvastatin reduced Lp(a) and substantially but not significantly lowered TG. However, in patients with the highest TG levels, HDLc was also significantly improved.

Topics: Adult; Aged; Cholesterol, LDL; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lovastatin; Male; Middle Aged; Pyrazines; Simvastatin; Treatment Outcome; Triglycerides

The aim of this study was to evaluate the lipid-lowering effect of acipimox as compared to pravastatin in patients with combined hyperlipidemia. One hundred and six subjects, all males, aged 18-60 years, with total cholesterol (TC) > or = 200 mg/dl, TC/HDL-C ratio > or = 5, triglycerides (TG) > or = 200 and > or = 350 mg/dl were randomized to receive acipimox 250 mg thrice daily or pravastatin 20 mg once daily for 3 months, according to a double-blind, double-dummy design. After a 1-month wash-out period patients were crossed to the alternative regimen for further 3 months. Prior to and at the end of each treatment period, TC, LDL-C, HDL-C, TG, blood glucose, and fibrinogen were evaluated. Both acipimox and pravastatin significantly decreased TC, LDL-C, TC/HDL-C ratio and TG and increased HDL-C, without affecting plasma glucose. However, at the dosages employed in the study acipimox was more effective in reducing TG and increasing HDL-C levels, whereas pravastatin was more efficient in decreasing TC and LDL-C. There was no difference between the 2 treatments in their effects on TC/HDL-C ratio. Unlike pravastatin acipimox caused a slight but significant reduction in fibrinogen plasma levels. No serious adverse event was observed with either drug, but a major incidence of side-effects was reported during treatment with acipimox. Our findings suggest that, although both drugs at the standard dose employed in the study were effective in improving the lipid profile; in the treatment of combined hyperlipidemia acipimox might be preferable in the presence of more pronounced hypertriglyceridemia with low levels of HDL-C, whereas pravastatin might be more useful when hypercholesterolemia is predominant.

Topics: Adolescent; Adult; Cross-Over Studies; Double-Blind Method; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipids; Male; Middle Aged; Patient Compliance; Pravastatin; Pyrazines

Hyperlipidemia, hypertriglyceridemia in particular, is a common feature in patients with noninsulin dependent diabetes mellitus (NIDDM) and may associate with insulin insensitivity. Acipimox, being widely prescribed for treating hypertriglyceridemia, is also used in NIDDM patients for their dyslipidemia. In the present study, we evaluated the effect of acipimox in Chinese NIDDM patients with hypertriglyceridemia. A total of 16 patients enrolled in a double-blind, randomized, placebo-controlled and two-period crossover study. After an 8 week run-in period, patients were randomly assigned into two groups receiving either acipimox (250 mg, twice daily) or placebo treatment. A total of 12 weeks later, these two groups switched their treatment for an additional 12 weeks. Blood samples were collected at the end of the run-in period and then at 4-week intervals in the whole study for lipid profile. A modified insulin suppression test was performed at the ends of the run-in period, 12-week and 24-week treatment to assess changes in insulin sensitivity. Our results showed that acipimox significantly lowered serum total triglyceride while compared to those by placebo. However, no difference was observed in serum non-esterified fatty acid, low-density lipoprotein cholesterol, total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and HDL-C/ TC ratio between the two groups. Furthermore, glycemic indices and insulin sensitivity were similar during the base-line, placebo or acipimox periods. Taken together, our data suggest that acipimox significantly lowered TG without perturbation of insulin sensitivity in hypertriglyceridemic NIDDM patients.

Topics: Adult; Aged; Apolipoprotein A-I; Apolipoproteins B; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperlipidemias; Hypertriglyceridemia; Hypolipidemic Agents; Insulin; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Pyrazines; Triglycerides

Patients with Type 2 diabetes are at increased risk from macrovascular disease whether or not they are hyperlipidaemic. Several factors may contribute to this increased risk including abnormalities of lipoprotein composition. The aim of our study was to determine the effects of lipid lowering drugs on lipoprotein composition (lipoprotein fractions were separated by sequential flotation ultracentrifugation) and insulin sensitivity (measured by a modified Harano technique) in 44 patients with mild hyperlipidaemia. All patients had total cholesterol concentrations between 5.2 and 6.5 mmol l-1 and total triglyceride concentrations < 3.0 mmol l-1, and were randomized by minimization to receive treatment for 12 weeks with bezafibrate, acipimox, simvastatin or placebo. Total cholesterol concentrations were decreased by simvastatin, 5.7 +/- 0.4 to 3.7 +/- 0.6 mmol l-1 (p < 0.05), due mainly to reduced LDL-cholesterol levels (-1.25 mmol l-1; p < 0.05), and bezafibrate 5.7 +/- 0.6 to 4.6 +/- 0.4 mmol l-1 (p < 0.05). The LDL:HDL-cholesterol ratio was reduced in the simvastatin group 2.0 +/- 0.5 to 1.2 +/- 0.3 (p < 0.005). There was no effect of the drugs on glycated haemoglobin or insulin sensitivity. In conclusion bezafibrate and simvastatin improve the lipid profile in Type 2 diabetic patients without adversely affecting diabetic control.

Topics: Apolipoproteins B; Bezafibrate; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Hypolipidemic Agents; Lovastatin; Middle Aged; Phospholipids; Placebos; Pyrazines; Simvastatin; Triglycerides

This study examines the effect of nicotinic acid (1 g t.d.s.) on serum Lp(a) concentration in a group of patients with type II hyperlipidaemia selected on the basis of a plasma Lp(a) concentration greater than 30 mg/dl. Reductions in total cholesterol, triglyceride, LDL-cholesterol and Lp(a) were 16.3%, 25.5%, 23.7% and 36.4%, respectively, with an increase in HDL cholesterol of 37.3%. The reduction in Lp(a) concentration did not correlate with any other lipoprotein changes. In order to establish the mechanism of the fall in Lp(a) concentration, in vivo turnover of autologous Lp(a) was studied in three subjects before and whilst taking nicotinic acid. The fractional catabolic rate in Lp(a) was unaltered in the subjects on therapy, indicating that nicotinic acid did not increase catabolism of Lp(a) but decreased the synthetic rate. Since nicotinic acid was poorly tolerated we examined the effect of acipimox, an analogue of nicotinic acid on lipoproteins using a placebo controlled double-blind crossover design in a group of hyperlipidaemic patients again selected with plasma Lp(a) concentration greater than 30 mg/dl. Acipimox was better tolerated than nicotinic acid but the percentage changes in lipoprotein concentrations were smaller.

Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoprotein(a); Male; Middle Aged; Niacin; Pyrazines; Triglycerides

Pharmacological suppression of lipolysis is being increasingly used in the treatment of diabetic hyperlipidaemia. Although theoretical hazard of such treatment is that recovery from hypoglycaemia might be impaired. Seven normal subjects were therefore studied on two occasions, following treatment with a single dose of either acipimox 250 mg or placebo. Hypoglycaemic recovery was unaffected, despite effective suppression of plasma non-esterified fatty acid levels with acipimox. The results suggest that under these conditions activation of lipolysis may not be essential to recovery from hypoglycaemia.

Topics: Acetoacetates; Adult; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Fatty Acids, Nonesterified; Female; Glycerol; Humans; Hyperlipidemias; Hypoglycemia; Hypolipidemic Agents; Insulin; Lipolysis; Male; Pyrazines

The side effect profiles and lipid lowering efficacy of nicotinic acid (1 g three times daily) and its analogue acipimox (250 mg three times daily) in type 2b hyperlipidaemia were compared in a double-blind placebo controlled study. In the nicotinic acid group (n = 7) at 12 weeks there were significant reductions (P less than 0.05) with respect to placebo (n = 9) in total cholesterol (median and range) 6.6 mmol l-1 (4.8-8.4) vs 8.8 mmol l-1 (7.5-9.5), triglyceride 1.4 mmol l-1 (0.5-4.6) vs 2.8 mmol l-1 (1.5-9.5) and apoprotein B 88.6 mg dl-1 (62.1-114) vs 121.9 mg dl-1 (88.0-170.7). In contrast there was no significant alteration in lipids in the acipimox group (n = 12). Nicotinic acid was associated with a high incidence of side effects, principally cutaneous flushing, while acipimox was well tolerated by all patients.

Topics: Adult; Aged; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipids; Male; Middle Aged; Niacin; Pyrazines

Fifty-two patients with Fredrickson Type IIb or Type IV hyperlipidaemia, in whom diet had not achieved satisfactory lipid levels, completed a double blind randomised study of acipimox versus placebo. The patients were given acipimox, 250 mg three times daily or placebo for a three month period, and plasma lipids and glucose were monitored. The patients receiving acipimox showed a fall in the mean concentration of plasma triglyceride compared to placebo (0.74 mmol/l) and this was most marked in patients whose initial plasma triglyceride levels were greater than 3 mmol/l (1.0 mmol/l, confidence limits 0.18, 1.82). Acipimox was well tolerated, and could be a useful addition to the drugs available for the treatment of patients with hypertriglyceridaemia.

Topics: Adult; Double-Blind Method; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Pyrazines; Random Allocation; Triglycerides

The hypolipidemic effect of acipimox, a new inhibitor of lipolysis, was investigated in a double blind crossover trial versus placebo. The trial showed an appreciable and significant reduction in total cholesterol (-14%) and of LDL cholesterol (-20%), a slight but significant increase in HDL cholesterol (+6%), and only a slight diminution of triglycerides and VLDL cholesterol.

Topics: Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Placebos; Pyrazines

Nicotinic acid has been used clinically for over 40 years in the treatment of dyslipidemia producing a desirable normalization of a range of cardiovascular risk factors, including a marked elevation of high density lipoprotein and a reduction in mortality. The precise mechanism of action of nicotinic acid is unknown, although it is believed that activation of a G(i)-G protein-coupled receptor may contribute. Utilizing available information on the tissue distribution of nicotinic acid receptors, we identified candidate orphan receptors. The selected orphan receptors were screened for responses to nicotinic acid, in an assay for activation of G(i)-G proteins. Here we describe the identification of the G protein-coupled receptor HM74 as a low affinity receptor for nicotinic acid. We then describe the subsequent identification of HM74A in follow-up bioinformatics searches and demonstrate that it acts as a high affinity receptor for nicotinic acid and other compounds with related pharmacology. The discovery of HM74A as a molecular target for nicotinic acid may facilitate the discovery of superior drug molecules to treat dyslipidemia.

Topics: Amino Acid Sequence; Animals; Cell Membrane; CHO Cells; Cricetinae; Databases as Topic; DNA, Complementary; Dose-Response Relationship, Drug; Female; Furans; Humans; Hyperlipidemias; Hypolipidemic Agents; Inhibitory Concentration 50; Male; Molecular Sequence Data; Niacin; Oocytes; Protein Binding; Pyrazines; Rats; Receptors, Nicotinic; RNA, Messenger; Sequence Homology, Amino Acid; Tissue Distribution; Xenopus

Topics: Adult; Bezafibrate; Cholesterol, HDL; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Pyrazines

Topics: Humans; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Hypolipidemic Agents; Pyrazines

The effect of Olbetam on serum lipid and lipoproteins was studied in 30 diabetic patients with hyperlipidemia in four weeks trial. The dose of Olbetram was 500 mg/d. The results showed serum concentrations of TC, TG, and VLDL-C were decreased while HDL-C especially HDL2-C increased significantly after treatment. There were no significant changes in FBG, blood creatinine and urine acid. This result suggests Olbetam can improve dyslipidemia in NIDDM and was well tolerated by all patients.

Topics: Adult; Cholesterol; Cholesterol, HDL; Cholesterol, VLDL; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Pyrazines; Triglycerides

The efficacy and safety of acipimox, an antilipolytic agent, were studied in 10 uremic patients under hemodialysis (group A) and in 8 renal transplant recipients with adequate renal function (group B). The medication was given for 20 weeks at a dose of 250 mg daily in both groups. Total serum cholesterol decreased significantly from 218.1 +/- 17.4 to 175.2 +/- 15.2 mg/dL (-19.7%) in group A and from 261.2 +/- 16.5 to 215.3 +/- 26.9 mg/dL (-17.6%) in group B; as did serum triglycerides, from 206.7 +/- 26.9 to 146.9 +/- 17.6 mg/dL (-29%) in group A and from 168.2 +/- 20.6 to 111.3 +/- 12.4 mg/dL (-33.8%) in group B. Low-density lipoprotein (LDL)-cholesterol and very low-density lipoprotein (VLDL)-cholesterol were also decreased significantly (LDL-C by -27% and -25%, and VLDL-C by -29.2% and -33.8% in groups A and B, respectively). Furthermore, the high-density lipoprotein (HDL)-cholesterol was increased significantly, by +29.6% in group A and +18% in group B. The apolipoproteins Apo-A1 and Apo-A2 were decreased in Group A but not in group B. The Apo-B was decreased in group B. Serum CPK (total and muscle fraction), total bilirubin, SGPT, SGOT, alkaline phosphatase, gamma GT, LDL, a-Fp, and creatinine remained unchanged in both groups. Acipimox seems to be effective in the regulation of atherogenic lipid disorders in hemodialysis patients and renal transplant recipients, without any muscular damage or alteration of kidney and liver function.

Topics: Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Kidney Transplantation; Lipids; Male; Middle Aged; Pyrazines; Renal Dialysis; Uremia

In studies performed in vivo and in vitro, it has been found that the Stokes' diameter of human low-density lipoproteins (LDL) correlates positively and significantly with the molar ratio of phospholipid/apo B in LDL but not with the LDL molar ratios of either cholesterol/apo B or triacylglycerol/apo B. It has been concluded that the phospholipid content of LDL is an important determinant of LDL size.

Topics: Apolipoproteins B; Cholesterol; Electrophoresis, Polyacrylamide Gel; Humans; Hyperlipidemias; Lipoproteins, LDL; Molecular Weight; Phospholipids; Pyrazines; Triglycerides

Topics: Acanthosis Nigricans; Adult; Axilla; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Nicotinic Acids; Pyrazines

Atherosclerotic manifestations are more common and precocious in diabetics than in the general population. Due to the increased cardiovascular risk, a primary or secondary (to diabetes mellitus) lipoprotein disorder in diabetics has to be carefully considered. 27 diabetics (15 NIDDM and 12 IDDM) with dyslipidemia (14 type IV, 8 type IIa and 5 type IIb) were divided in 3 groups and treated with 3 different hypolipemic drugs (Group A: pantethine 600 mg/day; Group B: acipimox 500 mg/day; Group C: bezafibrate 600 mg/day) to test their efficacy and acceptancy. Body weight, Hb A1-c, serum lipoproteins have been measured before and during the 6 months treatment. A significant variation of lipidemic pattern was observed in Group C: a decrease of cholesterol (-20%), triglycerides (-40%), LDL (-24.4%) and apo B (-26.8%) with an increase of HDL (+23.6%). Pantethine and acipimox were more effective on triglycerides (-37.7% and -23.3% respectively). Cardiovascular risk (CT tot/CT HDL) was significantly reduced with acipimox and normalized with bezafibrate.

Topics: Bezafibrate; Cardiovascular Diseases; Diabetes Complications; Humans; Hyperlipidemias; Hypolipidemic Agents; Pantetheine; Pyrazines; Risk Factors

The efficacy and tolerance of 750 mg of Acipimox was tested in 38 pts with primary dyslipidemias: 20 type IIa, 12 type IIb, and 6 type IV. All pts had been poor responders to a 2 month diet according to the recommendations of the National Cholesterol Education Program. Clinical examination, eye fundus, and the following laboratory tests: total cholesterol (TC), HDL, triglycerides (TG), total bilirubin, alkaline phosphatase, oxalacetic and pyruvic transaminases, uric acid, plasmatic creatinine, albumin, postprandial glucose test, hematocrit, white blood and platelet count were performed 60 days before drug initiation, 60 and 180 days after treatment had been started. No side effects were observed (myositis, visual gastrointestinal). 50% of the pts had slight to moderate flushing which appeared the first 3 days and lasted 14 +/- 7 days after treatment had been started. Plasmatic creatinine increased from 0.89 to 1.86 mg/dl in pt with one kidney, returning to normal levels 30 days after Acipimox interruption. After 180 days of therapy in the IIa group TC was -27% (p < 0.001), HDL + 15% (p < 0.001); in the IIb group: TC-23% (p < 0.001), HDL +9% (NS), TG -48% (p < 0.001); and in the IV group: TC-10% (p < 0.05), HDL +20% (p < 0.001), TG-53% (p < 0.001). Acipimox is well tolerated and is useful as a lipid-lowering drug in type IIa, IIb and IV dyslipidemias. Further studies are necessary to clear effects of the drug on renal metabolism and on long term survival of coronary pts.

Topics: Adolescent; Adult; Aged; Cholesterol; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Pyrazines; Triglycerides

Twenty-one patients with type II hyperlipidaemia were treated with the nicotinic acid analogue, acipimox (Olbetam; Farmitalia), for 6 months. Total cholesterol decreased by 10% and the high-density lipoprotein: low-density lipoprotein cholesterol ratio increased by 13%. Triglycerides were unaltered. Two patients stopped the drug after developing gastro-intestinal side-effects. Acipimox therapy warrants ongoing use and further investigation.

Topics: Cholesterol; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Pyrazines

In an open, uncontrolled study, the hypolipidaemic effect of acipimox was evaluated in 34 patients with Types IIa, IIb, IV or V hyperlipidaemia. Doses of 250 mg twice daily or 250 mg 3-times daily were maintained over a 12-week treatment period. The reduction in total plasma cholesterol levels was small and not statistically significant; however, significant increases in high density lipoproteins were achieved. Triglyceride levels were significantly lowered in patients with Type IV hyperlipidaemia. Acipimox was well tolerated by patients and no biochemical or haematological changes were noted. Considerable resolution in tubo-eruptive xanthomata was observed in 1 patient with Type V hyperlipidaemia.

Topics: Adult; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipids; Lipoproteins; Male; Middle Aged; Pyrazines

Topics: Adolescent; Adult; Aged; Cholesterol; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Pyrazines; Triglycerides