Diabetes Metab J.  2011 Apr;35(2):101-106. 10.4093/dmj.2011.35.2.101.

The Causes and Consequences of Low Levels of High Density Lipoproteins in Patients with Diabetes

Affiliations
  • 1The Heart Research Institute, Sydney, Australia. barterp@hri.org.au

Abstract

Type 2 diabetes is commonly accompanied by a low level of high density lipoprotein cholesterol (HDL-C) that contributes to the increased cardiovascular risk associated with this condition. Given that HDLs have the ability to improve increase the uptake of glucose by skeletal muscle and to stimulate the secretion of insulin from pancreatic beta cells the possibility arises that a low HDL concentration in type 2 diabetes may also contribute to a worsening of diabetic control. Thus, there is a double case for raising the level of HDL-C in patients with type 2 diabetes: to reduce cardiovascular risk and to improve glycemic control. Approaches to raising HDL-C include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. Of currently available drugs, the most effective is niacin. Newer formulations of niacin are reasonably well tolerated and have the ability to increase HDL-C by up to 30%. The effect of niacin on cardiovascular events in type 2 diabetes is currently being tested in a large-scale clinical outcome trial.

Keyword

Diabetes mellitus, type 2; High density lipoprotein; Insulin secretion; Insulin resistance; Lifestyle

MeSH Terms

Cholesterol
Cholesterol, HDL
Diabetes Mellitus, Type 2
Glucose
Humans
Insulin
Insulin Resistance
Insulin-Secreting Cells
Life Style
Lipoproteins
Lipoproteins, HDL
Motor Activity
Muscle, Skeletal
Niacin
Smoke
Smoking
Weight Loss
Cholesterol
Cholesterol, HDL
Glucose
Insulin
Lipoproteins
Lipoproteins, HDL
Niacin
Smoke

Figure

  • Fig. 1 Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters (CE) from high density lipoproteins (HDLs) to triglyceride-rich lipoproteins (TGR-LPs) in exchange for triglyceride (TG) to generate HDLs that are depleted of CE and enriched in TG. This TG enrichment provides HDLs with the preferred substrate for hepatic lipase. Subsequent hydrolysis of the newly acquired HDL TG by hepatic lipase leads to a reduction in volume of the particle core, a consequent decrease in particle size and a dissociation of lipid-free/lipid-poor apolipoprotein (apo) A-I from the HDL particle surface. The dissociation of lipid-poor apoA-I from HDLs provides an explanation for why the concentrations of both HDL-C and apoA-I tend to be low in states of hypertriglyceridemia such as occur in type 2 diabetes. Given that free fatty acids (FFAs) enhance the CETP-mediated remodelling of HDLs, such remodelling (and the associated low levels of HDL-C and apoA-I) may be exaggerated in patients with type 2 diabetes, a condition in which the concentration of FFAs in plasma is elevated as a consequence of the associated insulin resistance.


Cited by  1 articles

Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension
You-Cheol Hwang, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Edward J. Boyko
Diabetes Metab J. 2019;43(1):114-122.    doi: 10.4093/dmj.2018.0053.


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