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Coronary heart disease in diabetes mellitus: three new risk factors and a unifying hypothesis
1Department of Medicine, University College London Medical School, Whittington Hospital, UK.
Insights
Standard diabetes risk factors do not explain increased cardiovascular risk. New factors like plasminogen activator inhibitor, proinsulin-like molecules, and microalbuminuria may contribute to this excess risk in diabetic patients.
Area of Science:
- Cardiology
- Diabetology
- Metabolic Syndrome
Background:
- Standard cardiovascular risk factors (dyslipidemia, hypertension, smoking) inadequately explain the elevated cardiovascular risk in diabetes.
- Diabetic individuals face a significant reduction in life expectancy, largely due to cardiovascular complications.
- Existing risk factor interventions offer limited impact on mitigating this mortality gap.
Purpose of the Study:
- To explore novel risk factors contributing to the excess cardiovascular risk observed in diabetic populations.
- To investigate the roles of plasminogen activator inhibitor, proinsulin-like molecules, and microalbuminuria in diabetes-related cardiovascular disease.
- To examine potential shared antecedents, such as early nutrition, for these risk factors and cardiovascular outcomes.
Main Methods:
- Review of existing literature and recent findings on novel cardiovascular risk factors in diabetes.
- Analysis of the association between plasminogen activator inhibitor levels and thrombotic events/reinfarction.
- Exploration of correlations between proinsulin-like molecules and other risk factors, and the link between microalbuminuria and cardiovascular risk.
Main Results:
- Elevated plasminogen activator inhibitor in diabetics may increase thrombotic events and impair fibrinolysis.
- Increased proinsulin-like molecules correlate with other risk factors, but causality is unproven.
- Microalbuminuria strongly indicates cardiovascular risk, potentially linked to early nutrition and the insulin resistance syndrome.
Conclusions:
- Plasminogen activator inhibitor, proinsulin-like molecules, and microalbuminuria are potential contributors to diabetes-associated cardiovascular risk.
- The mechanisms linking these factors to cardiovascular disease require further elucidation.
- Early life factors, including nutrition, may play a role in the development of insulin resistance syndrome and subsequent cardiovascular disease in diabetic individuals.
Abstract:
The standard risk factors--dyslipidaemia, hypertension and smoking--provide little help in explaining the raised cardiovascular risk in diabetes. It can be calculated that intervening for disturbances of these risk factors could do little to rectify the loss of life expectancy of around 10 years for a middle-aged diabetic man. Three new risk factors are discussed, which together may contribute to some of the excess cardiovascular risk in diabetes. Plasminogen activator inhibitor is an inhibitor of fibrinolysis which is elevated in concentration in diabetic subjects, and may increase both the incidence of thrombotic events and the risk of reinfarction after the initial infarct. Recent work also suggests that high activity of this substance may impair pharmacological fibrinolysis. Proinsulin-like molecules are elevated in concentration in diabetic patients and correlate with levels of a number of other risk factors. Whilst these correlations may represent cause and effect for plasminogen activator inhibitor, there is no evidence that changes in levels of proinsulin-like molecules influence levels of other risk factors. Microalbuminuria provides a powerful indicator of cardiovascular risk in both diabetic and non-diabetic subjects, but whilst the mechanisms for this association are unclear, they are again unlikely to be mediated through changes in levels of standard risk factors. Recent observations of an association between short stature and microalbuminuria suggest that intrauterine or early infant nutrition may represent a common antecedent, these having also been shown to predict both components of the insulin resistance syndrome and cardiovascular disease in adult life.