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-dependent diabetes mellitus (NIDDM) have an increased risk of coronary artery disease partly attributable to clustering of risk factors in association with insulin resistance. Circulating levels of some hemostatic factors predict coronary events, and there is growing evidence that insulin 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 Willebrand factor (vWF) occur (1) in first-degree relatives of NIDDM patients and (2) in association with recognized features of insulin resistance.


RESULTS
Fasting blood samples were taken from 132 first-degree relatives of NIDDM patients and 151 age matched control subjects for measurement of FVII:C, fibrinogen, vWF, insulin, total and HDL cholesterol, triglyceride, glucose, and HbAIC. 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 significant difference in levels of vWF (0.98 versus 0.95 IU/mL). There was a graded association with features of insulin resistance, which was strongest for FVII:C, weaker for fibrinogen, and weakest for vWF.


CONCLUSIONS
FVII:C and fibrinogen levels are increased in relatives of patients with NIDDM. Levels of FVII:C and, to a lesser extent, fibrinogen and vWF cluster with other risk factors associated with insulin resistance. Abnormalities of circulating hemostatic factors, possibly in relation to insulin resistance, may contribute to cardiovascular risk in relatives of patients with NIDDM.
Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, UK. michaelm@pathology.leeds.ac.uk
M W
MW
Mansfield
D M
DM
Heywood
P J
PJ
Grant
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005091:Exons / Q000235:genetics; D005167:Factor VII / Q000235:genetics / Q000378:metabolism*; D005192:Family Health; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D014841:von Willebrand Factor / Q000378:metabolism*
D014841:von Willebrand Factor; D005167:Factor VII; D005340:Fibrinogen