Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia

Abstract

Glucose and lipid metabolism are linked to each other in many ways. The most important clinical manifestation of this interaction is diabetic dyslipidemia, characterized by elevated triglycerides, low high density lipoprotein cholesterol (HDL-C), and predominance of small-dense LDL particles. However, in the last decade we have learned that the interaction is much more complex. Hypertriglyceridemia and low HDL-C cannot only be the consequence but also the cause of a disturbed glucose metabolism. Furthermore, it is now well established that statins are associated with a small but significant increase in the risk for new onset diabetes. The underlying mechanisms are not completely understood but modulation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA)-reductase may play a central role as genetic data indicate that mutations resulting in lower HMG CoA-reductase activity are also associated with obesity, higher glucose concentrations and diabetes. Very interestingly, this statin induced increased risk for new onset type 2 diabetes is not detectable in subjects with familial hypercholesterolemia. Furthermore, patients with familial hypercholesterolemia seem to have a lower risk for type 2 diabetes, a phenomenon which seems to be dose-dependent (the higher the low density lipoprotein cholesterol, the lower the risk). Whether there is also an interaction between lipoprotein(a) and diabetes is still a matter of debate.

Keywords: Diabetes mellitus; Diabetic dyslipidemia; Hyperlipoproteinemia type II; Hyperlipoproteinemias; Statin.

Fig. 1. High density lipoprotein (HDL) may be linked to glucose metabolism in multiple ways. HDL (at least certain subtypes) have direct anti-inflammatory properties. HDL are also the central component of reverse cholesterol transport and mediate cholesterol efflux from many tissues. This may change the micro environment such that insulin sensitivity and insulin secretion improve.

Fig. 2. Animal studies indicate that knock-out and overexpression of apolipoprotein A1 (apoA1) affect many metabolic pathways related to diabetes development [21]. Whether the results observed in rodents are also valid in humans is unknown. HDL, high density lipoprotein; HbA1c, glycosylated hemoglobin.

Fig. 3. Statin therapy is associated with a small increase in new-onset diabetes type 2. The underlying pathophysiology is not well understood. A number of different mechanisms may lead to decreased insulin sensitivity and altered β-cell function. In predisposed subjects this may induce the manifestation of type 2 diabetes. HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A.