Endocrinol Metab.  2013 Sep;28(3):169-177. 10.3803/EnM.2013.28.3.169.

High Density Lipoprotein: A Therapeutic Target in Type 2 Diabetes

• Barter PJ

• KMID: 1973820
• DOI: http://doi.org/10.3803/EnM.2013.28.3.169

Abstract

High density lipoproteins (HDLs) have a number of properties that have the potential to inhibit the development of atherosclerosis and thus reduce the risk of having a cardiovascular event. These protective effects of HDLs may be reduced in patients with type 2 diabetes, a condition in which the concentration of HDL cholesterol is frequently low. In addition to their potential cardioprotective properties, HDLs also increase the uptake of glucose by skeletal muscle and stimulate the synthesis and secretion of insulin from pancreatic beta cells and may thus have a beneficial effect on glycemic control. This raises the possibility that a low HDL concentration in type 2 diabetes may contribute to a worsening of diabetic control. Thus, there is a double case for targeting HDLs in patients with type 2 diabetes: to reduce cardiovascular risk and also to improve glycemic control. Approaches to raising HDL levels include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. There is an ongoing search for HDL-raising drugs as agents to use in patients with type 2 diabetes in whom the HDL level remains low despite lifestyle interventions.

Keyword

Lipoproteins, HDL; Diabetes; Atherosclerosis

MeSH Terms

Atherosclerosis
Cholesterol, HDL
Glucose
Humans
Insulin
Insulin-Secreting Cells
Life Style
Lipoproteins, HDL
Motor Activity
Muscle, Skeletal
Smoke
Smoking
Weight Loss
Cholesterol, HDL
Glucose
Insulin
Lipoproteins, HDL
Smoke

Figure

• 

  Fig. 1 Low concentration of high density lipoprotein cholesterol (HDL-C) and apoA-I in patients with hypertriglyceridemia. Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters (CE) from high density lipoproteins (HDLs) to triglyceride-rich lipoproteins in exchange for triglyceride (TG). This generates HDL particles that are depleted of cholesteryl esters and enriched in triglyceride. This triglyceride enrichment provides HDLs with the preferred substrate for hepatic lipase that hydrolyses the newly acquired HDL TG. The resulting reduction in volume of the HDL particle core and consequent decrease in HDL particle size leads to the dissociation apolipoprotein (apo) A-I (the main HDL protein) from the HDL particle surface. The dissociated apoA-I may then be excreted in the urine and thus lost from the body. TGR-LP, triglyceride-rich lipoproteins; HL, hepatic lipase; FFA, free fatty acid.

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