HDL in diabetics is less protective than HDL in nondiabetics, but niacin can help restore some of its protective effects, according to a new study appearing in Circulation.

Investigators from Switzerland and Germany studied HDL from 10 healthy subjects and 33 patients with type 2 diabetes. Sajoscha Sorrentino and colleagues found that HDL from the healthy subjects, but not from the diabetics, stimulated endothelial nitric oxide production, reduced endothelial oxidant stress, and improved endothelium-dependent vasodilation and early endothelial progenitor cell–mediated endothelial repair, suggesting, “markedly impaired endothelial-protective properties of HDL.”

In the second part of the study, the diabetic patients were randomized to extended release (ER) niacin or placebo for 3 months. Niacin therapy enhanced stimulation of endothelial nitric oxide, reduced superoxide production, promoted endothelial progenitor cell-mediated endothelial repair, and reduced HDL oxidation.

Discussing their results in the context of recent interest (and disappointment) in CETP inhibitors, the authors write that “conceivably… plasma levels of HDL may not represent a reliable surrogate end point to predict vasoprotective effects of HDL-targeted therapies.” They note that the beneficial effects of HDL therapy in earlier studies “were observed with the use of either reconstituted HDL or HDL from healthy subjects,” and that “HDL from patients with coronary disease exerted a proinflammatory rather than an antiinflammatory effect.” They conclude by writing that “indexes of HDL functionality are urgently needed for assessment of the potential of HDLtargeted therapies to exert vasoprotective effects.”

PK Shah sent the following comment to CardioBrief:

“This is a very interesting, elegant and  informative study that shows that some of the potentially athero-protective endothelial functional properties of isolated HDL from diabetics with low HDL are impaired compared to HDL isolated from healthy nondiabetic subjects thereby supporting a wealth of recent data showing that all HDLs are not created equal and reinfrocing the evolving concept that HDL quality may be as or more important than HDL quantity; the findings that niacin can improve HDL quality , perhaps by reducing myeloperoxidase-induced oxidant damage to HDL, and not only HDL quantity is intriguing and a novel observation.The authors , unfortunately , did not assess cholesterol efflux promoting effects  of HDL; that would have been an important index of HDL functionality worth evaluating.”


Here is the press release from the AHA:

Good cholesterol not as protective in people with type 2 diabetes

Study highlights:

  • HDL, known as “good cholesterol,” helps protect blood vessels and the heart, but a small European study shows that HDL in men with type 2 diabetes lacks this protective capacity.
  • However, preliminary results indicate that extended-release niacin may help the HDL work better in these patients.

American Heart Association rapid access journal report:

DALLAS, Dec. 21, 2009 — High-density lipoprotein (HDL), known as “good” cholesterol, isn’t as protective for people with type 2 diabetes, according to research reported in Circulation: Journal of the American Heart Association.

HDL carries cholesterol out of the arteries, and high levels are associated with a lower risk of heart disease. HDL also helps protect blood vessels by reducing the production of damaging chemicals, increasing the vessels’ ability to expand, and repairing damage to the vessel lining.

Researchers at the University Hospital Zurich and the Medical School of Hannover in Germany and Switzerland compared the vessel-protecting action of HDL taken from 10 healthy adults with that of 33 patients who had type 2 diabetes and metabolic syndrome, a condition that includes having low HDL levels (under 40 mg/dL in men and 50mg/dL in women). The diabetes patients were taking cholesterol-lowering medication. In laboratory testing, investigators found that the protective benefits on blood vessels were “substantially impaired” in HDL from the diabetic patients.

The diabetics were then randomized to receive either a placebo or extended-release niacin (1500 milligrams/day), a medication that raises HDL cholesterol while reducing other blood fats. After three months, patients receiving extended-release niacin had increased HDL levels, and markedly improved protective functions of HDL in laboratory testing as well as improved vascular function.

However, because of the sample size and other factors that can’t be excluded, more research is needed to determine if niacin should be recommended for diabetic patients.

Co-lead authors are Sajoscha A. Sorrentino, M.D., and Christian Besler, M.D. Ulf Landmesser, M.D., is the senior and corresponding author.

Funding and author disclosures are on the manuscript.

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Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.americanheart.org/corporatefunding.

NR09 – 1182 (Circ/Sorrentino/Landmesser )

1 Comment

  1. Jay W. Heinecke at the University of Washington has done a lot of work in this area.

    Vaisar et al., Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J. Clin. Invest. 117(3): 746-756 (2007).

    Green, et al., Combined Statin and Niacin Therapy Remodels the High-Density Lipoprotein Proteome. Circulation. 2008;118:1259-1267.

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