Diabetic dyslipidemia

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Abstract

By the year 2025, there will be more than 300 million type 2 diabetes sufferers worldwide. This epidemic will be followed by a wave of cardiovascular disease. Diabetes is in fact a serious vascular disease with poor prognosis, and not only a disease characterized by elevated blood glucose. If adequate attention were paid to this, it would be much easier to relieve the burden of cardiovascular disease in type 2 diabetes patients. One important cardiovascular risk factor in type 2 diabetic people is dyslipidemia. This is characterized by low HDL-cholesterol, high serum VLDL-triglycerides, and a preponderance of small, dense LDL. Even slight elevations of LDL-cholesterol in type 2 diabetic patients are associated with a substantial increase in cardiovascular risk. The composition of lipid particles in diabetic dyslipidemia is more atherogenic than in dyslipidemia in general. This means in turn that normal lipid concentrations are more atherogenic in diabetic than in non-diabetic patients. Retrospective analyses show that, in terms of protection from cardiovascular endpoints, the benefit of lipid lowering in type 2 diabetic patients is at least as great as in the non-diabetic population. Lowering of LDL-cholesterol is a very attractive target for the reduction of coronary heart disease in type 2 diabetic people.

Introduction

The poor cardiovascular prognosis of diabetes is reflected by the findings of a Finnish study [1]. Type 2 diabetic patients without previous myocardial infarction have the same risk of dying from cardiovascular disease within 8 years as non-diabetic patients with prior myocardial infarction.

These Finnish data were confirmed by a recent study in six different populations in different parts of the world [2]. This study also showed that diabetic patients without previous cardiovascular disease and non-diabetic patients with cardiovascular disease have a similar risk of suffering cardiovascular death or a new myocardial infarction (Fig. 1). The direct implication of this finding is that it is essential to prevent initial myocardial infarction in diabetes sufferers, in order to relieve the burden of coronary heart disease.

Section snippets

High prevalence of dyslipidemia

The most significant cardiovascular risk factor in type 2 diabetic patients is dyslipidemia. The key components of diabetic dyslipidemia are elevation of serum VLDL-triglycerides and lowering of HDL-cholesterol. LDL-cholesterol, however, is usually not increased, or only slightly.

In the UKPDS study [3], the initial triglyceride, HDL-cholesterol and LDL-cholesterol levels were not so much different in diabetic and non-diabetic people. A finding such as this may give physicians the wrong

Diabetes-specific increase in CVD risk

The influence of multiple risk factors on cardiovascular mortality was investigated in the MRFIT study [4]. A total cholesterol>5.2 mmol/l, smoking, and a systolic blood pressure above 120 mmHg were regarded as risk factors in this study. Even in diabetic people without any of these risk factors, the cardiovascular death rate was higher than in a non-diabetic cohort without other risk factors. Together with the number of risk factors, the cardiovascular death rate increased in both the diabetic

Small, dense LDL

Diabetic dyslipidemia is a complex cluster of abnormalities. In addition to high LDL-cholesterol and low HDL-cholesterol, the serum triglycerides are elevated, there is excessive postprandial lipemia, a preponderance of small, dense LDL (LDL-phenotype pattern B), and, together with a lowering of HDL-cholesterol, a preponderance of small, dense HDL.

Small, dense LDL is a strong risk factor for cardiovascular disease and is considered to be highly atherogenic. It is also associated with the high

HDL changes

In diabetic dyslipidemia, not only the concentration of HDL-cholesterol is reduced, but also its composition and distribution is changed. The electrophoretic spectrum shows a shift towards smaller HDL-particles and HDL2 is reduced [14]. Changes in HDL in type 2 diabetes are mediated via two pathways: plasma triglyceride elevation, and a reduced ratio between lipoprotein lipase and hepatic lipase. Both lead to a modulation of HDL composition with an enhanced catabolic rate of HDL in circulation.

Conclusion

Altogether, three main lipoprotein particles cause atheroma: small, dense LDL; small, dense HDL; and cholesterol-ester rich remnants resulting from elevation of triglyceride-rich lipoproteins. All these components are elevated in diabetic patients.

In addition, normal lipid concentrations are more atherogenic in diabetic patients than non-diabetic patients due to changes in the composition of lipid particles. This forms the basis for the recommendations that in diabetic patients LDL-cholesterol

References (15)

  • M. Syvänne et al.

    High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease

    J. Lipid Res.

    (1995)
  • S.M. Haffner et al.

    Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction

    New Engl. J. Med.

    (1998)
  • Malmberg K, Yusuf S, Gerstein HC, Brown J, Zhao F, Hunt D, Piegas L, Calvin J, Keltai M, Budaj A for the OASIS Registry...
  • UK Prospective Diabetes Study 27. Plasma lipids and lipoproteins at diagnosis of NIDDM by age and sex

    Diabetes Care

    (1997)
  • J. Stamler et al.

    Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the multiple risk factor intervention trial

    Diabetes Care

    (1993)
  • R.C. Turner et al.

    Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS:23)

    Br. Med. J.

    (1998)
  • B.V. Howard et al.

    Adverse effects of diabetes on multiple cardiovascular disease risk factors in women. The Strong Heart Study

    Diabetes Care

    (1998)
There are more references available in the full text version of this article.

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