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Insulin sensitivity and haemostatic factors in men at high and low cardiovascular risk. The Risk Factor Intervention
1Department of Medicine, Sahlgrenska University Hospital, Göteborg University, Sweden. agewall@ss.gu.se
Insights
Men at high cardiovascular risk show greater insulin resistance, linked to impaired fibrinolysis and higher fibrinogen levels. This suggests that insulin resistance can contribute to endothelial dysfunction even in non-diabetic individuals.
Area of Science:
- Cardiovascular Disease Research
- Metabolic Syndrome Studies
- Hemostasis and Thrombosis Research
Background:
- Insulin resistance is a key factor in cardiovascular disease (CVD) development.
- The interplay between coagulation/fibrinolysis systems and insulin sensitivity in CVD risk stratification requires further investigation.
- Non-diabetic individuals with CVD risk factors may exhibit subclinical metabolic and hemostatic abnormalities.
Purpose of the Study:
- To examine the association between coagulation and fibrinolysis markers and insulin sensitivity in non-diabetic men.
- To compare these associations between high-risk and low-risk groups for cardiovascular disease.
- To identify specific hemostatic factors contributing to insulin resistance in different CVD risk strata.
Main Methods:
- Cross-sectional study involving 35 high-risk and 23 low-risk non-diabetic men.
- Insulin sensitivity assessed via hyperinsulinemic euglycemic clamp, adjusted for lean body mass.
- Measurements included fibrinogen, von Willebrand factor, prothrombin fragment 1+2, thrombin/antithrombin complex, and plasminogen activator inhibitor activity.
Main Results:
- High-risk men exhibited significantly lower insulin-mediated glucose disposal compared to low-risk men.
- Glucose disposal was negatively associated with plasminogen activator inhibitor (PAI) activity in high-risk individuals.
- Fibrinogen and PAI were significantly associated with glucose disposal in the overall cohort; PAI independently predicted glucose disposal in high-risk men.
Conclusions:
- Men at high CVD risk demonstrate increased insulin resistance.
- Impaired fibrinolytic activity, indicated by PAI, is linked to reduced glucose disposal in high-risk individuals.
- Fibrinogen is associated with insulin resistance across the study group, and von Willebrand factor may indicate early endothelial dysfunction in low-risk individuals.
Objective:
To investigate the relationship between variables of the coagulation and fibrinolysis system and insulin sensitivity in non-diabetic men at high and low risk of cardiovascular disease.
Design:
Cross-sectional study.
Setting:
Outpatient clinic in city hospital.
Patients:
Thirty-five men at high risk for atherosclerotic disease (hypertension and at least one the following factors: hypercholesterolaemia and smoking) and an age-matched low-risk group (n = 23) with no cardiovascular risk factors.
Main Outcome Measures:
Insulin-mediated glucose disposal (hyperinsulinaemic euglycaemic clamp) adjusted for lean body mass and fibrinogen, von Willebrand factor, prothrombin fragment 1 + 2, thrombin/antithrombin complex and plasminogen activator inhibitor activity were determined.
Results:
Insulin-mediated glucose disposal adjusted for lean body mass was significantly lower in the high-risk group than in the low-risk group. Glucose disposal was significantly negatively associated with plasminogen activator inhibitor activity (PAI) in the high-risk group and with von Willebrand factor in the low-risk group. In the whole study group, fibrinogen and PAI were significantly associated with glucose disposal. After adjusting for confounding factors, glucose disposal was independently negatively associated with PAI in the high-risk group (P < 0.001) and in the whole group (P < 0.001).
Conclusions:
High-risk men were significantly more insulin-resistant than the low-risk group. Glucose disposal adjusted for lean body mass was associated with an impaired fibrinolytic activity in the high-risk group. Fibrinogen was associated with insulin resistance in the whole study group. The negative relationship between von Willebrand factor levels and glucose disposal in the low-risk group may indicate that insulin resistance can induce an endothelial dysfunction even in non-diabetic subjects.
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