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Objective: Long-term treatment with up to 1.8 mg liraglutide improves cardiovascular and all-cause mortality in patients with type 2 diabetes at high risk for cardiovascular disease (CVD) and is currently under investigation in subjects without diabetes. Aim of our study was to investigate whether high dose (3 mg) short-term (5 weeks) treatment with liraglutide in obese patients with no overt type 2 diabetes affects metabolites, lipid and lipoprotein profile and components of activin–follistatin axis in cardiovascular beneficial or detrimental way. Research design and methods: Twenty obese patients participated in a randomized, placebo-controlled, cross-over, double-blind study and were administrated liraglutide 3 mg or placebo for 5 weeks. Metabolites, fatty acids, lipid–lipoprotein profile and concentrations of activins and follistatins (250 parameters) were assessed in serum at start and completion of each treatment. Results: Concentrations of important cardiovascular markers such as total, free and remnant cholesterol were reduced with liraglutide before and after adjusting for weight loss. Similarly, reductions in number of small and medium size LDL particles and in their total lipid concentration were observed with liraglutide and partially weight-loss related. Tyrosine levels were reduced and behenic acid levels were increased whereas only minor changes were observed in HDL, VLDL and IDL. Concentrations of activin AB and follistatin were significantly reduced in liraglutide-treated group. Conclusions: Treatment of obese patients without overt type 2 diabetes with high dose of liraglutide for a short period of time induces changes in lipid–lipoprotein and hormonal profile that are suggestive of lower risk of atherosclerosis and CVD. Trial registration ClinicalTrials.gov Identifier: NCT02944500. Study ID Number 2015P000327. Registered November 2016 [ABSTRACT FROM AUTHOR]

Background: Non-fasting triglyceride-rich lipoproteins cholesterol (TRL-C) contributes to cardiovascular risk, in that it includes remnant cholesterol (RC). TRL-C is computed as total C - [LDL-C + HDL-C]. Such calculation applies only if LDL-C is directly measured, or obtained from a non-Friedewald's formula, a method as yet never benchmarked against independent markers of TRL burden. Methods: The Discriminant Ratio (DR) methodology was used in 120 type 2 diabetic patients in order: (i) to compute TRL-C from non-fasting lipids, (ii) to establish the performance of TRL-C and TRL-C/apoA-I (vs. TG-based markers) to grade TRLs and atherogenic dyslipidemia (AD), and (iii) to relate TRL-C with non-fasting TG. Results: Depending on apoB100 availability, TRL-C (mg/dL) can be derived from non-fasting lipids in two ways: (a) total cholesterol (TC) - [(0.0106 * TC - 0.0036 * TG + 0.017 * apoB100 - 0.27) * 38.6] - HDL-C, and (b) TC - [(0.0106 * TC - 0.0036 * TG + 0.017 * [0.65 * (TC - HDL-C) + 6.3] - 0.27) * 38.6] - HDL-C. Discrimination between log[TG] and TRL-C was similar (DR 0.94 and 0.84, respectively), whereas that of log[TG]/HDL-C was better than TRL-C/apoA-I (DR 1.01 vs. 0.65; p 0.0482). All Pearson's correlations between pairs reached unity, allowing formulation of two unbiased equivalence equations: (a) TRL-C = 97.8 * log[TG] - 181.9, and (b) TRL-C/apoA-I = 8.15 * (log[TG]/HDL-C) - 0.18. Conclusions: TRL-C and log[TG] are as effective and interchangeable for assessing remnant atherogenic particles. For grading TRL-AD, it is best to use log[TG]/HDL-C, inherently superior to TRL-C/apoA-I, while measuring the same underlying variable. [ABSTRACT FROM AUTHOR]

Background: Four single nucleotide polymorphisms (SNPs) (rs2237892, rs2237895, rs2237897, and rs2283228) in KCNQ1 are reported to be associated with type 2 diabetes mellitus (T2DM), possibly caused by a reduction in insulin secretion and higher fasting glucose, but the results are inconsistent. We investigated whether these 4 genetic markers are associated with serum lipid metabolism in a middle-aged Chinese Han population. Methods: We enrolled 398 consecutive patients, including 180 with premature coronary artery disease (CAD) (male < 55 years, female < 65 years) and 218 controls without documented CAD. All subjects were genotyped for 4 SNPs by using the ligase detection reaction method. Fasting blood sugar (FBS) and plasma concentrations of total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDLC), apolipoprotein A1(apo A1), and apolipoprotein B (apo B) were determined by standard biochemical methods. Main anthropometric and metabolic characteristics are analyzed among 3 genotypes at rs2283228, rs2237895, rs2237897, or rs2237892 in KCNQ1. Results: The 3 genotypes AA, AC, and CC were present in rs2283228 and rs2237895, and the 3 genotypes CC, CT, and TT were present in rs2237897 and rs2237892. The minor genotypes CC at rs2283228 and TT at rs2237892 were associated with higher levels of TG (P = 0.007 and 0.026, respectively). Furthermore, subjects with the CC genotype at rs2283228 had lower levels of HDL-C and apo A1 than in the other 2 genotype groups (P = 0.052 and 0.055, respectively). No other associations were detected between these 4 SNPs and FBS or other lipid parameters. Conclusions: Our data suggest that rs2283228 and rs2237892 in KCNQ1 are associated with lipid metabolism in a middle-aged Chinese Han population. [ABSTRACT FROM AUTHOR]

Objective: The Use of Rosuvastatin versus Atorvastatin iN type 2 diabetes mellitUS (URANUS) study compared rosuvastatin with atorvastatin for the reduction of low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes. Methods: After a 6-week dietary run-in, patients aged = 18 years with type 2 diabetes and LDLC = 3.3 mmol/L were randomised to double-blind treatment with rosuvastatin 10 mg (n = 232) or atorvastatin 10 mg (n = 233) for 4 weeks. Doses were then titrated up to a maximum of rosuvastatin 40 mg or atorvastatin 80 mg over 12 weeks to achieve the 1998 European LDL-C goal (<3.0 mmol/L). Results: Rosuvastatin reduced LDL-C levels significantly more than atorvastatin during the fixeddose and titration periods (p < 0.0001). Significantly more patients reached the 1998 LDL-C goal with rosuvastatin 10 mg compared with atorvastatin 10 mg at 4 weeks (81% vs 65%, p < 0.001). At 16 weeks, significantly more patients achieved their LDL-C goal with rosuvastatin compared with atorvastatin (94% vs 88%, p < 0.05) and more patients receiving rosuvastatin remained at their starting dose with reduced requirement for dose titration. At 4 weeks, 65% of rosuvastatin patients had reached their 2003 European LDL-C goal (< 2.5 mmol/L), compared with 33% of atorvastatin patients (p < 0.0001). Both treatments were similarly well tolerated with no unexpected safety concerns. Conclusion: At the start dose and following dose titration, rosuvastatin was significantly more effective than atorvastatin at reducing LDL-C and achieving European LDL-C goals in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. Methods: Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6-3.9 mM/l and HDL cholesterol ⩽ 1.05 mM/l for women and ⩽ 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. Results: After 4 months, plasma triglyceride concentrations were decreased by 44% (p < 0.001). HDL cholesterol concentrations were increased by 10% (p < 0.001). Non-HDL cholesterol was decreased by 19%. A greater HDL cholesterol response was observed in lean patients (body mass index < 25 kg/m²) compared to the rest of the population (8.2 vs 19.7%, p < 0.001). In contrast, cases with excess body weight had a larger decrease in non-HDL cholesterol levels (-20.8 vs - 10.8%, p < 0.001). There were no significant complications resulting from treatment with ciprofibrate. Conclusions: Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated. [ABSTRACT FROM AUTHOR]