Elevated levels of plasma triglyerides (TG) and reduced concentrations of HDL cholesterol are very common in patients with diabetes, particularly NIDDM. Although regulation of the plasma concentrations of VLDL, the major TG-rich lipoprotein is extremely complex, it is clear from in vivo kinetic studies that increased rates of secretion of VLDL into plasma is almost uniformly present in patients with NIDDM and hyertriglyceridemia. Recent studies at the cellular level indicate that increased fatty acid flux to the liver, also common in NIDDM (and other insulin-resistant states associated with elevated plasma TG levels), will stimulate the assembly and secretion of apoprotein (apo) B-containing lipoproteins by targeting apoB for secretion rather than intracellular degradation. Increased rates of secretion of VLDL into plasma appears to drive the exchange of TG from these lipoproteins for HDL cholesteryl ester. This exchange, which occurs in plasma, is facilitated by cholesteryl ester transfer protein, and generates a TG-enriched HDL that is a substrate for either hepatic lipase or lipoprotein lipase. When the TG in HDL is hydrolyzed, the resultant particle is smaller, and this appears to affect the binding of the major HDL protein, apoA-I. ApoA-I dissociates from the smaller, lipid-poor HDL, and the free apoA-I (molecular weight 28,000) can be filtered by the glomerulus in the kidney and most likely is degraded in renal tubular cells after reabsorption. Thus, increased free fatty acid transport in plasma, a common abnormality in insulin-resistant states, may be the underlying driving force for the two common lipid abnormalities seen in diabetes.
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LIPOPROTEIN DISORDERS IN DIABETES|
July 01 1996
Diabetic Dyslipidemia: Basic Mechanisms Underlying the Common Hypertriglyceridemia and Low HDL Cholesterol Levels
Henry N Ginsberg
Henry N Ginsberg
Department of Medicine, Columbia University College of Physicians and Surgeons
New York, New York
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Address correspondence and reprint requests to Dr. Henry N. Ginsberg, Irving Professor of Medicine, Department of Medicine, Columbia University College of Physiciansand Surgeons, 630 W. 168th St., New York, NY 10032
Citation
Henry N Ginsberg; Diabetic Dyslipidemia: Basic Mechanisms Underlying the Common Hypertriglyceridemia and Low HDL Cholesterol Levels. Diabetes 1 July 1996; 45 (Supplement_3): S27–S30. https://doi.org/10.2337/diab.45.3.S27
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