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 Mell itus prospectively studied insulin-treated patients with type 2 (non-insuli n-dependent) diabetes mellitus, achieving 2.1% glycosylated hemoglobin sepa ration between intensive- and standard-treatment arms (P<.001) for 2 years. Objective: To assess the effect of intensive therapy on serum fibrinogen an d lipid levels, compared with standard treatment. Methods: One hundred fifty-three male subjects with type 2 diabetes mellitu s and who required insulin treatment were recruited from 5 Veterans Affairs medical centers. The subjects were divided into intensive- and standard-tr eatment arms for a randomized prospective study. Dyslipidemia was managed i dentically in both arms (diet, drugs). Fibrinogen levels and lipid fraction s 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 +/- 0.1 4 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 chang e in the standard-treatment arm. Cholesterol levels decreased in the intens ive-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-tr eatment arm. Levels of low- and high-density lipoprotein cholesterol decrea sed 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 apolipop rotein A(1) levels decreased in the standard-treatment arm (P<.01). Lipopro tein (a) levels did not change in either treatment arm. Lipid results were essentially identical whether examined in the full cohort or excluding thos e patients receiving hypolipidemic agents. Conclusions: Intensive insulin therapy led to a potentially beneficial redu ction in serum triglyceride levels and preservation of high-density lipopro tein cholesterol and apolipoprotein A(1) levels. However, it caused transie nt elevation in plasma fibrinogen levels, a possible thrombogenic effect.