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Low-density-lipoprotein cholesterol concentrations and risk of incident diabetes: epidemiological and genetic insights from the Framingham Heart Study.

Abstract：

AIMS/HYPOTHESIS:Statins and niacin (nicotinic acid) reduce circulating LDL-cholesterol (LDL-C) levels by different mechanisms. Yet, both increase the risk of diabetes mellitus. Our objective was to relate blood LDL-C concentrations and a genetic risk score (GRS) for LDL-C to the risk of incident diabetes in individuals not treated with lipid-modifying therapy. METHODS:We evaluated participants of the Framingham Heart Study who attended any of Offspring cohort examination cycles 3-8 and Third Generation cohort examination cycle 1 (N =14,120 person-observations, 6,011 unique individuals; mean age 50 ± 11 years, 56% women), who were not treated with lipid-modifying or antihypertensive medications and who were free from cardiovascular disease at baseline. Incident diabetes was assessed at the next examination. RESULTS:The GRS was significantly associated with LDL-C concentrations (sex- and age-adjusted estimated influence 0.24, p < 0.0001). On follow-up (mean 4.5 ± 1.5 years), 312 individuals (2.2%) developed new-onset diabetes. In multivariable models, a higher LDL-C concentration was associated with lower risk of diabetes (OR per SD increment 0.81, 95% CI 0.70, 0.93, p = 0.004). The GRS was associated with incident diabetes in a similar direction and of comparable magnitude (OR per SD increment 0.85, 95% CI 0.76, 0.96, p = 0.009). CONCLUSIONS/INTERPRETATION:Among individuals not treated with lipid-modifying therapy low LDL-C concentrations were associated with increased diabetes risk. These observations may contribute to our understanding of why lipid-lowering treatment may cause diabetes in some individuals. Additional studies are warranted to elucidate the molecular mechanisms underlying our observations.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Andersson C,Lyass A,Larson MG,Robins SJ,Vasan RS

doi

10.1007/s00125-015-3762-x

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

2774-80

issue

eissn

0012-186X

issn

1432-0428

pii

10.1007/s00125-015-3762-x

journal_volume

pub_type

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Low-density-lipoprotein cholesterol concentrations and risk of incident diabetes: epidemiological and genetic insights from the Framingham Heart Study.