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Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome.
Aye, MM, Kilpatrick, ES, Afolabi, P, Wootton, SA, Rigby, AS, Coady, AM, Sandeman, DD, Atkin, SL
Diabetes, obesity & metabolism. 2014;(6):545-52
Abstract
AIM: This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. METHODS In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention. RESULTS By 12 weeks, niacin/laropiprant lowered low-density lipoprotein cholesterol (LDL-c) (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP. CONCLUSIONS In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β-cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.
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Graft loss risk in renal transplant recipients with metabolic syndrome: subgroup analyses of the ALERT trial.
Soveri, I, Abedini, S, Holdaas, H, Jardine, A, Eriksson, N, Fellström, B
Journal of nephrology. 2012;(2):245-54
Abstract
BACKGROUND Several nonimmunologic risk factors for late renal graft loss (RGL) are also known components of metabolic syndrome (MS). We aimed to study MS as a risk factor for RGL. Also, the effect of statin treatment in reducing renal risk in renal transplant recipients (RTRs) with MS was studied. METHODS Nondiabetic RTRs (n=1,706) from the ALERT trial were followed for 7-8 years. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III definition with waist girth replaced by BMI ≥30 (calculated as kg/m(2)). Renal end points included death-censored RGL and graft loss or doubling of serum creatinine. RESULTS During the follow-up, 284 patients experienced RGL, and there were 343 cases of graft loss or doubling of serum creatinine. Those with MS had increased risk for RGL (relative risk = 1.28, 95% confidence interval, 1.00-1.63; p=0.047), but not for the combined end point. After adjustment for other known and potential risk factors, MS was no longer associated with increased risk for RGL. The association between MS and RGL risk was attenuated once adjustment for creatinine was made. Statin treatment did not reduce the risk for renal end points in RTRs with or without MS. CONCLUSION MS had no independent association with RGL risk. Adjustment for renal function attenuated the association between MS and RGL.
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Extended-release niacin/laropiprant effects on lipoprotein subfractions in patients with type 2 diabetes mellitus.
Bays, H, Giezek, H, McKenney, JM, O'Neill, EA, Tershakovec, AM
Metabolic syndrome and related disorders. 2012;(4):260-6
Abstract
BACKGROUND A potentially atherogenic lipid profile often found in patients with type 2 diabetes mellitus (T2DM) includes increased concentrations of small, low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL) and decreased concentration of medium/large high-density lipoprotein (HDL) particles. Extended-release niacin/laropiprant (ERN/LRPT) lowers LDL-cholesterol (LDL-C) and triglycerides (TG), and raises HDL cholesterol (HDL-C) levels with attenuation of niacin-induced flushing. METHODS Plasma HDL, LDL, IDL, very-low-density lipoprotein (VLDL), and chylomicron particle concentration and size at were evaluated at baseline and week 12 using nuclear magnetic resonance (NMR). The data were acquired from a randomized, multicenter, double-blind, placebo-controlled study including 796 patients with T2DM treated with either 1 tablet of ERN 1 gram/LRPT 20 mg or matching placebo daily, increased after 4 weeks to 2 tablets daily. RESULTS ERN/LRPT significantly (P≤0.001 for all) reduced LDL-C 17.9% and TG 23.1%, and increased HDL-C levels 23.2%. Compared to placebo, ERN/LRPT decreased LDL, IDL, VLDL, and chylomicron particle concentrations [median concentration of smallest LDL particles decreased 16.6%, 95% confidence interval (CI) -22.3, -10.9, whereas the largest LDL particles decreased 11.0%, 95% CI -18.7, -3.2, and total VLDL/chylomicron mean plasma particle concentration decreased 34.7%, 95% CI -41.3, -28.1]. Compared to placebo, ERN/LRPT shifted the distribution of HDL particle diameter from smaller to larger (median concentration of the largest HDL particles increased 32.7% (95% CI 25.30, 40.58), whereas concentration of the smallest HDL particles decreased 8.2% (95% CI -11.29, -5.06). CONCLUSIONS Compared with placebo in patients with T2DM, ERN/LRPT shifted the lipoprotein profile toward a potentially less atherogenic pattern with reduced atherogenic LDL and IDL particle concentrations, and increased large HDL plasma particle concentrations. (ClinicalTrials.gov: NCT00485758).
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Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone.
De Hert, M, Mittoux, A, He, Y, Peuskens, J
European archives of psychiatry and clinical neuroscience. 2011;(4):231-9
Abstract
The presence of the metabolic syndrome is an important risk factor for cardiovascular disease and diabetes. The short- and long-term metabolic safety of sertindole was compared to that of risperidone in a subset of patients enrolled in the sertindole cohort prospective (SCoP) study, an open randomized study. In 261 randomized patients, there were moderate increases in mean weight, BMI, and waist circumference during treatment with either sertindole or risperidone; after 12 weeks, the increase in weight was 1.3 and 1.1 kg, respectively, and after 36 weeks, it was 2.2 and 2.0 kg, respectively. From baseline to last assessment (up to 60 weeks), weight gains of 1.8 and 1.7 kg for sertindole and risperidone, respectively, were observed. Similar proportions of patients (sertindole: 17% versus risperidone: 16%) had weight increases ≥7% from baseline to last assessment. The mean changes from baseline in triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, plasma glucose and blood pressure were small and not clinically relevant in both treatment groups. No patient in either of the groups developed type 2 diabetes during the study. At last assessment, the prevalence of metabolic syndrome (International Diabetes Federation) was 17% in the sertindole group and 26% in the risperidone group and the incidence of metabolic syndrome was 7% in the sertindole group and 10% in the risperidone group. Treatment with either sertindole or risperidone did not appear to be associated with an increased comparative risk of developing metabolic syndrome. In general, the metabolic effects of sertindole and risperidone were similar.
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Different galenic formulations of fluvastatin have equal lipid-lowering potential but differ in reducing lipemia-induced endothelial dysfunction.
Westphal, S, Abletshauser, C, Luley, C
Coronary artery disease. 2009;(1):81-5
Abstract
BACKGROUND Postprandial lipemia is known to exert a reversible detrimental effect on endothelium-dependent flow-mediated vasodilation (FMD). Fasting FMD has shown to be improved by fluvastatin. In this study, we investigated whether lipemia-induced endothelial dysfunction can be mitigated by fluvastatin in two (immediate-release and extended-release) formulations. METHODS In 27 patients with the metabolic syndrome, randomized in a three-period crossover design for 5 weeks each to 80 mg extended-release fluvastatin daily, 40 mg immediate-release fluvastatin twice daily (b.i.d.) or placebo, the fasting and postprandial lipids and FMD of the brachial artery were measured at baseline and after 5 weeks of each treatment period. Postprandial lipemia was induced by administration of whipping cream containing 33% fat (1 g fat/kg body weight). FMD was determined by two-dimensional ultrasonography of the brachial artery in the fasting state and 4 h after the fatty meal. Lipids were determined using routine methods. RESULTS Fasting triglycerides were reduced after immediate-release and extended-release fluvastatin by 16 and 23%, respectively, and postprandial triglycerides by 20 and 29%, respectively. The fasting FMD was also improved by each treatment. The postprandial FMD impairment, however, was mitigated only after 40 mg b.i.d. After 80 mg fluvastatin, the last dose of which had been administered the previous evening, the lipemic FMD impairment was the same as after the placebo. CONCLUSION Fluvastatin improves fasting FMD regardless of whether it is administered as 40 mg b.i.d. or 80 mg daily given in the evening. The lipemic FMD impairment, in contrast, is improved only by 40 mg b.i.d. when the tablet is taken in the morning of the test day. As the half-life of fluvastatin is about 2 h, we surmise that an improvement occurs only when sufficient amounts of fluvastatin are present in the bloodstream.
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Reduced risk of new-onset diabetes with trandolapril/verapamil-SR in patients with the metabolic syndrome.
Cardiovascular journal of Africa. 2007;(3):190
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Fluvastatin lowers atherogenic dense low-density lipoproteins in postmenopausal women with the atherogenic lipoprotein phenotype.
März, W, Scharnagl, H, Abletshauser, C, Hoffmann, MM, Berg, A, Keul, J, Wieland, H, Baumstark, MW
Circulation. 2001;(15):1942-8
Abstract
BACKGROUND Although HMG-CoA reductase inhibitors (HMGRIs) are effective lipid-lowering agents, it remains controversial whether these agents also lower dense LDL (dLDL), a predominance of which is considered to contribute to the atherogenicity of the metabolic syndrome. METHODS AND RESULTS In a multicenter, double-blind, randomized, placebo-controlled study, we determined the effect of the HMGRI fluvastatin on lipids, apolipoproteins, and LDL subfractions (by equilibrium density gradient ultracentrifugation). A total of 52 postmenopausal women with combined hyperlipidemia and increased dLDL were treated with either fluvastatin 40 mg/d (n=35) or placebo (n=17). After 12 weeks' treatment, significant reductions (P<0.001) in total cholesterol (-19%), IDL cholesterol (-35%), LDL cholesterol (-23%), apolipoprotein B (-21%), and apolipoprotein B in dLDL (-42%) were apparent among fluvastatin recipients. No significant changes in triglycerides or HDL cholesterol were observed. The effect of fluvastatin on dLDL was correlated with baseline values. There was no consistent relationship, however, between the effect of fluvastatin on triglycerides and the decrease in dLDL. CONCLUSIONS Fluvastatin lowers total and LDL cholesterol and the concentration of dLDL. This profile may contribute to an antiatherogenic effect for fluvastatin that is greater than expected on the basis of changes in lipids and apolipoproteins.