CIRCULATING LEVELS OF FACTOR-VII, FIBRINOGEN, AND VON-WILLEBRAND-FACTOR AND FEATURES OF INSULIN-RESISTANCE IN FIRST-DEGREE RELATIVES OF PATIENTS WITH NIDDM

Background First-degree relatives of patients with non-insulin-depende nt diabetes mellitus (NIDDM) have an increased risk of coronary artery disease partly attributable to clustering of risk factors in associat ion with insulin resistance. Circulating levels of some hemostatic fac tors predict coronary events, and there is growing evidence that insul in resistance is also associated with abnormalities of coagulation and fibrinolysis. This study examined the hypotheses that elevated levels of factor VII coagulant activity (FVII:C), fibrinogen, and von Willeb rand factor (vWF) occur (1) in first-degree relatives of NIDDM patient s and (2) in association with recognized features of insulin resistanc e.Methods and Results Fasting blood samples were taken from 132 first- degree relatives of NIDDM patients and 151 age-matched control subject s for measurement of FVII:C, fibrinogen, vWF, insulin, total and HDL c holesterol, triglyceride, glucose, and HbA(1c). Levels of FVII:C (130% versus 122%, P<.02) and fibrinogen (3.0 versus 2.7 g/L, P=.002) were higher in relatives than in control subjects, and there was no signifi cant difference in levels of vWF (0.98 versus 0.95 IU/mL). There was a graded association with features of insulin resistance, which was str ongest for FVII:C, weaker for fibrinogen, and weakest for vWF. Conclus ions FVII:C and fibrinogen levels are increased in relatives of patien ts with NIDDM. Levels of FVII:C and, to a lesser extent, fibrinogen an d vWF cluster with other risk factors associated with insulin resistan ce. Abnormalities of circulating hemostatic factors, possibly in relat ion to insulin resistance, may contribute to cardiovascular risk in re latives of patients with NIDDM.