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Prevalence
and Nature of dyslipidemia in diabetes mellitus
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- Diabetes
mellitus is associated with an increased risk of cardiovascular
disease. In both types of diabetes, abnormalities of lipid metabolism
are prevalent, but the nature of these abnormalities is different.
- In case
of type 1 (insulin-dependent) diabetes mellitus, poor glycemic
control and the presence of nephropathy is associated with lipid
abnormalities.
- Dyslipidemia
is observed in practically all patients of type 2 (noninsulin-dependent)
diabetes. Lipid abnormalities are observed even in those with
good glycemic control and in the absence of any renal disease.
The most common pattern of dyslipidemia in these patients is
elevated triglyceride levels and decreased HDL cholesterol levels.
The concentration of LDL cholesterol in type 2 diabetic patients
is usually not significantly different from nondiabetic individuals.
However, type 2 diabetic patients typically have a preponderance
of smaller, denser LDL particles, which increases atherogenicity
even if concentration of LDL is not significantly increased.
Insulin resistance is a strong candidate as the underlying abnormality
responsible for all these changes.
The following
table outlines the lipid abnormalities observed in diabetic patients.
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Lipid
and lipoprotein abnormalities in diabetes mellitus
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Diabetes
Category |
Lipids
and Lipoproteins |
| Type
1 diabetes |
| Usual
levels of glycemia (Euglycemia) |
Similar
to non-diabetic population
|
| Poor
glycemic control |
Increased
triglycerides
Increased LDL susceptibility to oxidation |
| Diabetic
nephropathy |
Increased
LDL cholesterol
Decreased HDL cholesterol
Increased lipoprotein(a) |
| Type
2 diabetes |
| Usual
levels of glycemia (Euglycemia) |
Increased
triglycerides
Decreased HDL cholesterol
Small, dense, LDL particles
Increased LDL susceptibility to oxidation
|
| Poor
glycemic control |
Worsening
of hypertriglyceridemia
|
| Diabetic
nephropathy Increased triglycerides |
Decreased
HDL cholesterol
Increased lipoprotein (a)
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| Risks
associated with diabetic dyslipidemia |
- Both type
1 and type 2 diabetes mellitus are associated with increased
risk of CHD.
- Studies
have shown that blood glucose and/or insulin levels may be associated
with an increased risk of CHD in diabetic patients.
- Further,
the risk of CHD among diabetic patients is directly related
to the levels of blood pressure, cigarette smoking and total
cholesterol. At any level of these risk factors, diabetic patients
probably have four to five times the risk of CHD among NIDDM
patients.
- The Joslin
Clinic study showed that 35% of patients with type 1 diabetes
died from CHD before the age of 55. In patients with type 1
diabetes, the presence of nephropathy increases the risk of
CHD 15 fold.
- The Framingham
study showed that risk of cardiovascular death was increased
4.5 fold in women and 2 fold in men with predominantly type
2 diabetes.
- Seventy
five to 80% of adult diabetic patients die from coronary heart
disease (CHD), cerebrovascular disease and/or peripheral vascular
disease.
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| Etiology
of diabetic dyslipidemia |
- Insulin
deficiency reduces lipoprotein lipase (LPL) activity and results
in defective removal of triglyceride-rich lipoproteins. The
dyslipidemia seen in many diabetic patients - high triglycerides
and low HDL cholesterol - is associated with low LPL activity.
- Low cholesteryl
ester transfer protein (CETP) is observed in NIDDM patients
while its activity tends to be high in IDDM patients. Cholesteryl
ester transfer protein mediates the exchange of cholesteryl
esters in HDL particles for triglycerides in VLDL particles.
It may be therefore important for reverse cholesterol transport.
Accordingly, high CETP activity might inhibit atherosclerosis
by accelerating the removal of excess cholesterol from the arterial
wall. However, CETP produces VLDL particles that are cholesteryl-ester
enriched and ultimately decreases HDL levels - two potentially
atherogenic lipoprotein changes observed commonly in diabetes.
- LDL levels
may not be significantly elevated in diabetic patients. However,
they may be modified to forms that promote atherogenesis. For
example, nonenzymatic glycation may cause LDL to be rapidly
internalized by macrophages, thus accelerating the process of
atherosclerosis. Elevated glucose levels may also favour the
production of oxidized LDL, the first step in the process of
atherosclerosis.
- Reduced
HDL cholesterol levels may be due to increased catabolism, resulting
from increased hepatic triglyceride lipase action of HDL particles
with higher triglyceride content.
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