Pathophysiology of Diabetic Dyslipidemia

Area of Science:

• Cardiovascular Medicine
• Metabolic Disorders
• Lipid Metabolism

Background:

• Atherosclerotic cardiovascular disease (ASCVD) risk is significantly elevated in type 2 diabetes.
• Serum triglyceride (TG) is a potent predictor of ASCVD, comparable to LDL-cholesterol (C).
• Diabetic dyslipidemia involves elevated TG-rich lipoproteins (TRLs), small dense LDL, and low HDL2-C.

Purpose of the Study:

• To review the role of insulin resistance in VLDL overproduction.
• To discuss the clinical relevance of specific LDL and HDL subspecies.
• To overview dyslipidemia in diabetic kidney disease (DKD).

Main Methods:

• Review of experimental and clinical observations.
• Introduction of direct assays for quantifying small dense LDL-C and HDL3-C.
• Explanation of calculating HDL2-C from total HDL-C and HDL3-C.

Main Results:

• Insulin resistance, not hyperinsulinemia, stimulates hepatic VLDL production.
• Small dense LDL and HDL2 subspecies are significantly impacted by insulin resistance.
• Diabetic kidney disease exacerbates dyslipidemia and atherogenic risk.

Conclusions:

• Understanding the interplay between insulin resistance, VLDL metabolism, and specific lipoprotein subspecies is crucial for managing ASCVD risk in diabetes.
• Novel assays for LDL and HDL subspecies offer clinical utility.
• DKD significantly contributes to dyslipidemia and cardiovascular risk.