New perspective on type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease

Abstract

Serum lipid abnormalities (dyslipidemias) are major risk factors for cardiovascular disease in type 2 diabetes mellitus. Recent findings provide new evidence that dyslipidemia characterized by elevated triglycerides and non-high-density lipoprotein cholesterol levels with a decreased high-density lipoprotein cholesterol level are risk factors for cardiovascular disease in patients with type 2 diabetes. There are multiple therapeutic agents to help patients to achieve target lipid levels, but understanding the molecular mechanisms could provide useful information for new treatment strategies for diabetic dyslipidemia.

Figure 1

The pathogenic interplay between type 2 diabetes, non‐alcoholic fatty liver disease (NAFLD)/non‐alcoholic steatohepatitis (NASH), dyslipidemia and cardiovascular disease, and the potential clinical targets for these complications. Insulin resistance and excess insulin stimulate the production of triglycerides (TGs) in the liver, which promotes the serum lipid accumulation and the development of NAFLD. Increased secretion of these lipids into the bloodstream causes diabetic dyslipidemia, characterized by elevated serum concentrations of TG‐rich very low‐density lipoprotein cholesterol (VLDL) and small dense low‐density lipoprotein (LDL) cholesterol, and low concentrations of high‐density lipoprotein (HDL) cholesterol. Consequently, all of these factors, combined with hyperglycemia, increase the risk for cardiovascular diseases. Recent studies showed that serum levels of tyrosine, angiopoietin‐like protein 8 (ANGPTL‐8), and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF), together with dyslipidemia, could be new biomarkers of type 2 diabetes and NAFLD. Recent studies also found dipeptidyl peptidase‐4 inhibitors, α7 nicotinic acetylcholine receptor (α7nAchR) agonist, Rho‐associated coiled‐coil‐containing kinase 1 (ROCK1) inhibitor, and hepatocyte growth factor (HGF) as novel and potential targets for the effective treatment of dyslipidemia and NAFLD in diabetes patients.