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Multiple CHD risk factors in type 2 diabetes: beyond hyperglycaemia
1Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA. greaven@cumed.stanford.edu
Insights
Achieving good glycaemic control is challenging and does not fully prevent coronary heart disease (CHD) in type 2 diabetes. Syndrome X, characterized by insulin resistance and associated metabolic abnormalities, accelerates atherosclerosis and increases cardiovascular risk.
Area of Science:
- Cardiology
- Endocrinology
- Metabolic Syndrome
Background:
- Good glycaemic control in type 2 diabetes mellitus (T2DM) improves microvascular outcomes but does not sufficiently reduce coronary heart disease (CHD) risk.
- Syndrome X, a cluster of insulin resistance-related abnormalities, is implicated in accelerating atherosclerosis and increasing cardiovascular risk in T2DM patients.
Purpose of the Study:
- To explore the role of Syndrome X in accelerating atherogenesis and cardiovascular risk in patients with type 2 diabetes.
- To highlight the complex interplay of metabolic abnormalities contributing to CHD in the context of insulin resistance.
Main Methods:
- Review of recent evidence, including the United Kingdom Prospective Diabetes Study.
- Analysis of the components of Syndrome X and their contribution to atherosclerosis.
- Examination of the impact of insulin resistance and hyperinsulinaemia on endothelial function and prothrombotic state.
Main Results:
- Syndrome X encompasses hypertension, hyperinsulinaemia, dyslipidaemia (small, dense LDL-C, high triglycerides, low HDL-C), and a procoagulant state.
- This dyslipidaemia and hyperinsulinaemia promote a prothrombotic state via plasminogen activator inhibitor-1.
- Insulin resistance accelerates plaque formation through increased endothelial adhesion molecules and monocyte adhesion.
Conclusions:
- Syndrome X and type 2 diabetes present multiple abnormalities that enhance the atherosclerotic process.
- Understanding the complex factors of insulin resistance, hyperinsulinaemia, and their link to CHD is crucial for developing new therapeutic strategies to reduce cardiovascular risk.
Abstract:
Recent evidence from the United Kingdom Prospective Diabetes Study convincingly demonstrates that good glycaemic control is difficult to achieve and, despite its positive impact on microvascular complications, is not sufficient to reduce the risk of coronary heart disease (CHD). Syndrome X--a cluster of abnormalities associated with resistance to insulin-mediated glucose uptake that have been implicated in accelerating atherogenesis--provides a useful clinical concept to prevent CHD in patients with type 2 diabetes. Components of syndrome X can include hypertension, hyperinsulinaemia, dyslipidaemia, and a procoagulant state, changes that contribute to the development of atherosclerosis. Low-density lipoprotein cholesterol (LDL-C) levels are usually close to normal, but the LDL-C is present in abnormally small and dense particles. Triglyceride levels are elevated and are associated with an increase in postprandial accumulation of atherogenic, remnant lipoprotein particles. High-density lipoprotein cholesterol levels are typically low. This particular dyslipidaemia, along with hyperinsulinaemia, induces expression of plasminogen activator inhibitor-1, contributing to a prothrombotic state. In addition, plaque formation may be accelerated in insulin-resistant subjects by increased expression of adhesion molecules on endothelial cells and increased rate of monocyte adhesion to cultured endothelial cells. Syndrome X and type 2 diabetes are associated with multiple abnormalities that enhance the atherosclerotic process. The opportunities for new therapeutic approaches to reduce cardiovascular risk will undoubtedly evolve along with our understanding of the complex factors responsible for insulin resistance, compensatory hyperinsulinaemia, and CHD.