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Original Investigation
December 7/21, 1998

Effect of Intensive Glycemic Control on Fibrinogen, Lipids, and Lipoproteins: Veterans Affairs Cooperative Study in Type II Diabetes Mellitus

Author Affiliations

From the Hines Veterans Affairs Hospital, Hines, Ill (Drs Emanuele, Azad, Abraira, Henderson, and Lee); Loyola University Medical Center, Maywood, Ill (Drs Emanuele, Azad, and Abraira); Diabetes Center, Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (Dr Colwell); Diagnostic and Treatment Center and Department of Medicine, Wadsworth Veterans Affairs Medical Center, Los Angeles, Calif (Dr Levin); Department of Medicine, University of California at Los Angeles Medical Center (Dr Levin); Medical Service, Veterans Affairs Medical Center and University of Minnesota Medical Center, Minneapolis (Dr Nuttall); Medical Service, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Tex (Dr Comstock); The Endocrine-Diabetes Section, Veterans Affairs Medical Center and Boston University School of Medicine, Boston, Mass (Drs Sawin and Silbert); and Northwest Lipid Research Laboratories, University of Washington, Seattle (Dr Marcovina). A complete list of participants and funding sources for the Veterans Affairs Cooperative Study in Type II Diabetes Mellitus Group has been published elsewhere (Diabetes Care. 1992;15:1560-1571).

Arch Intern Med. 1998;158(22):2485-2490. doi:10.1001/archinte.158.22.2485
Abstract

Background  The Veterans Affairs Cooperative Study in Type II Diabetes Mellitus prospectively studied insulin-treated patients with type 2 (non–insulin-dependent) diabetes mellitus, achieving 2.1% glycosylated hemoglobin separation between intensive- and standard-treatment arms (P<.001) for 2 years.

Objective  To assess the effect of intensive therapy on serum fibrinogen and lipid levels, compared with standard treatment.

Methods  One hundred fifty-three male subjects with type 2 diabetes mellitus and who required insulin treatment were recruited from 5 Veterans Affairs medical centers. The subjects were divided into intensive- and standard-treatment arms for a randomized prospective study. Dyslipidemia was managed identically in both arms (diet, drugs). Fibrinogen levels and lipid fractions were measured in the full cohort. Lipid fractions are separately reported in patients not treated with hypolipidemic agents.

Results  There were no baseline differences between arms. Fibrinogen levels rose in the intensive-treatment arm at 1 year (from 3.34±0.12 to 3.75±0.15 g/L; P<.001) but returned to baseline at 2 years (3.47±0.12 g/L). There was no change in the standard-treatment arm. Triglyceride levels decreased in the intensive-treatment arm from 2.25±0.27 to 1.54±0.14 mmol/L (199±24 to 136±12 mg/dL) at 1 year (P=.004) and to 1.74±0.18 mmol/L (154±16 mg/dL) at 2 years (P=.03); there was no change in the standard-treatment arm. Cholesterol levels decreased in the intensive-treatment arm at 1 year from 5.4±0.21 to 4.99±0.13 mmol/L (207±8 to 193±5 mg/dL) (P=.02); there was no change in the standard-treatment arm. Levels of low- and high-density lipoprotein cholesterol decreased in the standard-treatment arm only by 2 years, from 3.44±0.13 to 3.16±0.10 mmol/L (133±5 to 122±4 mg/dL) (P=.02) and from 1.10±0.03 to 1.00±0.03 mmol/L (42±1 to 38±1 mg/dL) (P<.001) for low-density and high-density lipoprotein cholesterol, respectively. Levels of apolipoprotein B decreased in both treatment arms (P<.001), and apolipoprotein A1 levels decreased in the standard-treatment arm (P<.01). Lipoprotein (a) levels did not change in either treatment arm. Lipid results were essentially identical whether examined in the full cohort or excluding those patients receiving hypolipidemic agents.

Conclusions  Intensive insulin therapy led to a potentially beneficial reduction in serum triglyceride levels and preservation of high-density lipoprotein cholesterol and apolipoprotein A1 levels. However, it caused transient elevation in plasma fibrinogen levels, a possible thrombogenic effect.

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