Document Detail


Concomitant reduction of low-density lipoprotein-cholesterol and biomarkers of inflammation with low-dose simvastatin therapy in patients with type 1 diabetes.
MedLine Citation:
PMID:  17519305     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Cardiovascular disease is a major cause of mortality in type 1 diabetes (TIDM). TIDM is a proinflammatory state. Whereas there is consensus on lipid management in type 2 diabetes, there is a lack of data in type 1 diabetes. In addition to benefits on the lipid profile, statin therapy is antiinflammatory.
OBJECTIVE: There are scant data on statin therapy in T1DM. Thus, we tested the effect of simvastatin, compared with placebo, on biomarkers of inflammation and monocyte function in TIDM patients.
DESIGN: This was a double-blind, randomized, placebo-controlled study of T1DM patients, randomized to placebo or simvastatin, 20 mg/d for 3 months.
SETTING: The study was conducted at the University of California, Davis, Medical Center.
PARTICIPANTS: Participants included patients with T1DM.
METHODS AND RESULTS: Analytes measured at baseline and 3 months included liver function tests, creatinine, hemoglobin AIC, high-sensitivity C-reactive protein, soluble CD40 ligand, monocyte O(2)(-), cytokines, nuclear factor-kappaB. Simvastatin therapy resulted in significant reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (18% reduction, P < 0.001) and soluble CD40 ligand (22% reduction, P < 0.05), compared with placebo. Simvastatin therapy significantly inhibited lipopolysaccharide-activated monocyte release of O(2)(-) (P < 0.0005), IL-8 (P < 0.03), and TNF (P < 0.02). Simvastatin therapy significantly inhibited monocyte IL-6 release, compared with baseline (P = 0.02). Simvastatin therapy also significantly reduced monocytic nuclear factor-kappaB p65 activity, compared with placebo (P < 0.01).
CONCLUSIONS: This study demonstrates that simvastatin (20 mg/d) is safe in T1DM patients and has concomitant benefits on the lipid profile and biomarkers of inflammation. These novel findings could have implications for developing policy guidelines for statin therapy in forestalling vascular complications in young T1DM.
Authors:
Ishwarlal Jialal; Eric Miguelino; Steven C Griffen; Sridevi Devaraj
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2007-05-22
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  92     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-08     Completed Date:  2007-09-17     Revised Date:  2013-01-23    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3136-40     Citation Subset:  AIM; IM    
Affiliation:
Laboratory for Atherosclerosis and Metabolic Research, University of California, Davis, Medical Center, Sacramento, California 95817, USA. ishwarlal.jialal@ucdmc.ucdavis.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Biological Markers
Cholesterol / blood
Cholesterol, LDL / blood*
Cytokines / blood
Diabetes Mellitus, Type 1 / blood*
Double-Blind Method
Female
Hemoglobin A, Glycosylated / metabolism
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Inflammation / metabolism*
Lipoproteins, LDL / blood*
Male
Monocytes / drug effects,  metabolism,  physiology
Simvastatin / therapeutic use*
Triglycerides / blood
Grant Support
ID/Acronym/Agency:
K24 AT000596-09/AT/NCCAM NIH HHS; K24 AT000596-10/AT/NCCAM NIH HHS; K24 AT00596/AT/NCCAM NIH HHS; R21 DK069801/DK/NIDDK NIH HHS; R21 DK069801-02/DK/NIDDK NIH HHS; R21DK69801/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cholesterol, LDL; 0/Cytokines; 0/Hemoglobin A, Glycosylated; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Lipoproteins, LDL; 0/Triglycerides; 57-88-5/Cholesterol; 79902-63-9/Simvastatin
Comments/Corrections

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