Pathophysiology of Diabetic Dyslipidemia

J Atheroscler Thromb. 2018 Sep 1;25(9):771-782. doi: 10.5551/jat.RV17023. Epub 2018 Jul 12.


Accumulating clinical evidence has suggested serum triglyceride (TG) is a leading predictor of atherosclerotic cardiovascular disease, comparable to low-density lipoprotein (LDL)-cholesterol (C) in populations with type 2 diabetes, which exceeds the predictive power of hemoglobinA1c. Atherogenic dyslipidemia in diabetes consists of elevated serum concentrations of TG-rich lipoproteins (TRLs), a high prevalence of small dense low-density lipoprotein (LDL), and low concentrations of cholesterol-rich high-density lipoprotein (HDL)2-C. A central lipoprotein abnormality is an increase in large TG-rich very-low-density lipoprotein (VLDL)1, and other lipoprotein abnormalities are metabolically linked to increased TRLs. Insulin critically regulates serum VLDL concentrations by suppressing hepatic VLDL production and stimulating VLDL removal by activation of lipoprotein lipase. It is still debated whether hyperinsulinemia compensatory for insulin resistance is causally associated with the overproduction of VLDL. This review introduces experimental and clinical observations revealing that insulin resistance, but not hyperinsulinemia stimulates hepatic VLDL production. LDL and HDL consist of heterogeneous particles with different size and density. Cholesterol-depleted small dense LDL and cholesterol-rich HDL2 subspecies are particularly affected by insulin resistance and can be named "Metabolic LDL and HDL," respectively. We established the direct assays for quantifying small dense LDL-C and small dense HDL(HDL3)-C, respectively. Subtracting HDL3-C from HDL-C gives HDL2-C. I will explain clinical relevance of measurements of LDL and HDL subspecies determined by our assays. Diabetic kidney disease (DKD) substantially worsens plasma lipid profile thereby potentiated atherogenic risk. Finally, I briefly overview pathophysiology of dyslipidemia associated with DKD, which has not been so much taken up by other review articles.

Keywords: Diabetes; HDL subspecies; Insulin resistance; Small dense LDL; Triglyceride-rich lipoproteins.

Publication types

  • Review

MeSH terms

  • Animals
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cholesterol, VLDL / blood
  • Chylomicrons / chemistry
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Nephropathies / physiopathology*
  • Dyslipidemias / physiopathology*
  • Fatty Acids, Nonesterified / blood
  • Glycated Hemoglobin / genetics
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Lipoproteins / blood
  • Lipoproteins, VLDL / blood
  • Liver / metabolism
  • Mice
  • Pioglitazone / pharmacology
  • Risk
  • Triglycerides / blood


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Cholesterol, VLDL
  • Chylomicrons
  • Fatty Acids, Nonesterified
  • Glycated Hemoglobin A
  • Insulin
  • Lipoproteins
  • Lipoproteins, VLDL
  • Triglycerides
  • hemoglobin A1c protein, human
  • lipoprotein triglyceride
  • Cholesterol
  • Pioglitazone