Diabetic Dyslipidemia: A Major Complication of Obesity and Diabetic States

Metabolic diseases particularly obesity, metabolic syndrome, and type 2 diabetes are increasing in prevalence and pose one of the major public health challenges worldwide. At least one quarter of the North American population has evidence of the metabolic syndrome and the prevalence is increasing. Metabolic syndrome describes a cluster of closely related risk factors for diabetes and cardiovascular disease (CVD), including abdominal obesity, hyperglycemia, hypertension, and dyslipidemia consisting primarily of hypertriglyceridemia and low HDL.This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments. An expert panel convened by the National Lipid Association has recently evaluated the use of selected biomarkers [C-reactive protein (CRP), lipoprotein-associated phospholipase A(2), apolipoprotein B (apoB), LDL particle concentration, lipoprotein(a), and LDL and HDL subfractions] to improve risk assessment, or to adjust therapy. These panel recommendations will be reviewed. Further emphasis will be given to important biomarkers including apoB and CRP. ApoB has received considerable attention in recent years as a more superior CHD risk biomarker when compared to LDL-cholesterol. LDL particles are composed primarily of cholesterol and are the most atherogenic lipoproteins in plasma. ApoB measurement makes possible to count directly the number of LDL particles in plasma. Subjects with hypertriglyceridemia (such as diabetics) have higher apoB and smaller/denser LDL particles.The typical dyslipidemia (also referred to by some as ‘the atherogenic dyslipidemia’) observed in diabetic states is characterized by a cluster of quantitative and qualitative lipid and lipoprotein abnormalities. This includes increased plasma concentrations of fasting and postprandial apoB-containing, triglyceride-rich lipoproteins (TRL, including VLDL and chylomicrons), reduced HDL particle number and cholesterol content as assessed by plasma apoA-I and HDL-C respectively, and a predominance of small, dense LDL particles. Altered metabolism of TRL, both overproduction and impaired clearance, is central to the pathophysiology of the atherogenic dyslipidemia. Abnormalities can also occur in postprandial states due to overproduction of triglyceride-rich chylomicron particles. Thus lipid and lipoprotein abnormalities are commonly observed in diabetic states in both fasting and postprandial states.In this lecture, I will discuss the pathophysiology of diabetic dyslipidemia and the important role of the Gut-Brain-Liver signaling network in metabolic health and the development of lipid disorders leading to atherosclerotic cardiovascular disease.