Effect of intensive glycemic control on fibrinogen, lipids, and lipoproteins: Veterans Affairs Cooperative Study in Type II Diabetes Mellitus

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 19325 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 highdensity 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.