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Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia.

ABSTRACT: OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment, administered alone or in sequence, on glucose and lipid metabolism, cardiovascular risk factors, and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia. RESEARCH DESIGN AND METHODS We studied 128 type 2 diabetic patients with mixed dyslipidemia complying throughout the study with lifestyle intervention who were randomized twice, initially to either metformin or placebo, and then to micronized fenofibrate or placebo. RESULTS Fenofibrate alleviated diabetic dyslipidemia-induced changes in plasma high-sensitivity C-reactive protein, fibrinogen, and plasminogen activator inhibitor (PAI)-1 and in monocyte cytokine release, whereas metformin or lifestyle intervention improved mainly glucose and lipid metabolism. The strongest pleiotropic effect was observed when fenofibrate was added to metformin. CONCLUSIONS Fenofibrate, particularly administered together with metformin, is superior to metformin and lifestyle intervention in exhibiting beneficial effects on systemic inflammation, hemostasis, and monocyte secretory function in type 2 diabetic patients with mixed dyslipidemia.

SUBMITTER: Pruski M

PROVIDER: S-EPMC2713621 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia.

Pruski Maciej M Krysiak Robert R Okopien Boguslaw B

Diabetes care 20090512 8

OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment, administered alone or in sequence, on glucose and lipid metabolism, cardiovascular risk factors, and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia. RESEARCH DESIGN AND METHODS We studied 128 type 2 diabetic patients with mixed dyslipidemia complying throughout the study with lifestyle intervention who were randomized twice, initially to either metformin or placebo, and then to micro ...[more]

PMID: 19435959

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Project description:HIV patients on antiretroviral therapy (ART) have a unique dyslipidemia [elevated triglycerides and non-high-density lipoprotein-cholesterol (HDL-C), low HDL-C] with insulin resistance (characterized by hypoadiponectinemia).The aim was to test a targeted, comprehensive, additive approach to treating the dyslipidemia.We conducted a randomized, double-blind, placebo-controlled, 24-wk trial of lifestyle modification, fenofibrate, and niacin in multiethnic HIV clinics at an academic center.Hypertriglyceridemic adult patients were stratified on three combinations of ART classes. Subjects retained at the first measurement (2 wk) after entry were included in the analysis (n = 191).Subjects were randomized into five treatment groups: usual care (group 1); low-saturated-fat diet and exercise (D/E; group 2); D/E + fenofibrate (group 3); D/E + niacin (group 4); or D/E + fenofibrate + niacin (group 5).We measured changes in fasting triglycerides, HDL-C, and non-HDL-C (primary), and in insulin sensitivity, glycemia, adiponectin, C-reactive protein, energy expenditure, and body composition (secondary). Data were analyzed as a factorial set of treatment combinations using a mixed repeated measures model, last observation carried forward, and complete case approaches (groups 2-5), and as an unstructured set of treatments (groups 1-5).Fenofibrate improved triglycerides (P = 0.002), total cholesterol (P = 0.02), and non-HDL-C (P = 0.003), whereas niacin improved HDL-C (P = 0.03), and both drugs decreased the total cholesterol-to-HDL-C ratio (P = 0.005-0.01). The combination of D/E, fenofibrate, and niacin provided maximal benefit, markedly reducing triglycerides (-52% compared to usual care; P = 0.003), increasing HDL-C (+12%; P < 0.001), and decreasing non-HDL-C (-18.5%; P = 0.003) and total cholesterol-to-HDL-C ratio (-24.5%; P < 0.001). Niacin doubled adiponectin levels.A combination of fenofibrate and niacin with low-saturated-fat D/E is effective and safe in increasing HDL-C, decreasing non-HDL-C and hypertriglyceridemia, and ameliorating hypoadiponectinemia in patients with HIV/ART-associated dyslipidemia.

Project description:Enterococci are Gram-positive bacteria present in the healthy human microbiota, but they are also a leading cause of nosocomial infections. Maltodextrin utilization by Enterococcus faecalis has been identified as an important factor for colonization of mammalians hosts. Here, we show that the LacI/GalR transcriptional regulator MalR, the maltose gene regulator, is also the main regulator of the operons encoding an ABC transporter (mdxEFG) and three metabolic enzymes (mmdH-gmdH-mmgT) required for the uptake and catabolism of maltotetraose and longer maltodextrins. The utilization of maltose and maltodextrins is consequently coordinated and induced by the disaccharide maltose, which binds to MalR. Carbon catabolite repression of the mdxEFG and mmdH-gmdH-mmgT operons is mediated by both P-Ser-HPr/MalR and P-Ser-HPr/CcpA. The latter complex exerts only moderate catabolite repression, which became visible when comparing maltodextrin operon expression levels of a malR- mutant (with a mutant allele for the malR gene) and a malR- ΔccpA double mutant grown in the presence of maltose, which is transported via a phosphotransferase system and, thus, favors the formation of P-Ser-HPr. Moreover, maltodextrin transport via MdxEFG slows rapidly when glucose is added, suggesting an additional regulation via inducer exclusion. This complex regulation of metabolic operons likely allows E. faecalis to fine-tune gene expression in response to changing environmental conditions.IMPORTANCEEnterococcus faecalis represents a leading cause of hospital-acquired infections worldwide. Several studies highlighted the importance of carbohydrate metabolism in the infection process of this bacterium. The genes required for maltodextrin metabolism are particularly induced during mouse infection and, therefore, should play an important role for pathogenesis. Since no data were hitherto available concerning the regulation of expression of the maltodextrin operons, we have conducted experiments to study the underlying mechanisms.

Dataset Information

Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia.

Publications

Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia.

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