Increased risk for diabetes development in subjects with large variation in total cholesterol levels in 2,827,950 Koreans: A nationwide population-based study

<div><p>Background</p><p>Recent studies suggest a role for hyperlipidemia in the development of diabetes. The aim of this study is to analyze the relationship between variations of total cholesterol (TC) levels and the risk for type 2 diabetes development from a Korean nationwide population-based database.</p><p>Materials and methods</p><p>We examined the General Health Check-up sub-dataset of the Korean National Health Insurance Service (NHIS) of 2,827,950 participants who had at least three health check-ups between 2002 and 2007, and were not reported to have diabetes during that time. The variations of TC levels between the examinations were calculated as follows: . The examinees were divided into 10 groups according to TC variation, and the hazard ratio for diabetes development from 2007 to 2013, were analyzed.</p><p>Results</p><p>During the follow-up period, 3.4% of the participants had developed diabetes. The hazard ratio (HR) for diabetes development relative to the overall risk in the whole study population started to be higher than 1.0 from eighth decile of TC variation. The highest decile group showed an increased HR for diabetes development after adjustment for confounding variables (1.139; 95% confidence interval 1.116~1.163). These results were similar regardless of the use of anti-hyperlipidemic medication and baseline TC levels.</p><p>Conclusions</p><p>The participants with a large variation in TC levels showed an increased risk for diabetes development, independent of the use of anti-hyperlipidemic medications. These results suggest a relationship between fluctuations in lipid levels and the development of type 2 diabetes.</p></div

General characteristics of the participants according to the development of diabetes in 2007.

<p>General characteristics of the participants according to the development of diabetes in 2007.</p

Disease-free survival curve for diabetes development according to the total cholesterol variation.

<p>Disease-free survival curve for diabetes development according to the total cholesterol variation.</p

HR for diabetes development according to deciles of TC variations.

<p>The HR in this graph express the risk in deciles compared with the average risk in whole study population. HR, hazard ratio; CI, confidence interval; TC, total cholesterol.</p

Hazard ratio for development of diabetes after adjustment for confounding factors.

<p>Hazard ratio for development of diabetes after adjustment for confounding factors.</p

Comparison of baseline characteristics according to baseline NAFLD status and hs-CRP levels.

<p>Comparison of baseline characteristics according to baseline NAFLD status and hs-CRP levels.</p

Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation

<div><p>Background</p><p>Recent studies have suggested the importance of non-alcoholic fatty liver disease (NAFLD) and systemic inflammation in the development of atherosclerosis. The aim of this study was to compare the risk for coronary artery calcification (CAC) development according to the status of NAFLD and inflammation over four years of follow-up in subjects without baseline CAC.</p><p>Methods</p><p>A total of 1,575 participants in a health screening program were divided into four groups according to baseline NAFLD state and high-sensitivity C-reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs-CRP <0.06 mg/L, no NAFLD and hs-CRP ≥0.06 mg/L, NAFLD and hs-CRP <0.06 mg/L, and NAFLD and hs-CRP ≥0.06 mg/L. Coronary artery calcium score (CACS) was repeatedly measured by multi-detector computed tomography at four-year intervals and CAC development during those intervals was monitored in subjects with baseline CACS = 0.</p><p>Results</p><p>Over four years, 148 subjects (9.4%) developed CAC. The proportion of subjects who developed CAC was significantly higher in subjects with NAFLD at baseline compared with those without NAFLD at baseline (6.8 vs. 12.4%, p<0.01), and it was also higher in subjects with hs-CRP ≥0.06 mg/L compared with those with hs-CRP <0.06 mg/L (7.2 vs. 11.5%, p<0.01). In addition, the proportion of subjects who developed CAC was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/dL, followed by subjects with NAFLD, subjects without NAFLD and hs-CRP ≥0.06 mg/L, and subjects without NALFD and hs-CRP <0.05 mg/L at baseline, in that order (13.7, 10.0, 8.3, and 5.8%, respectively; p for trend<0.01). The odds ratio for CAC development was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/L (1.67, 95% CI 1.01–2.77), though it was attenuated after adjustment for body mass index.</p><p>Conclusions</p><p>The concomitant presence of NAFLD and systemic inflammation as assessed by hs-CRP increases the risk of CAC development over four years.</p></div

Comparison of mean values of baseline metabolic parameters according to baseline quartiles^a of Lp(a) levels.

<p>Comparison of mean values of baseline metabolic parameters according to baseline quartiles<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177500#t002fn002" target="_blank">^a</a> of Lp(a) levels.</p

Additional file 1: Table S1. of The relationship between serum fatty-acid binding protein 4 level and lung function in Korean subjects with normal ventilatory function

Comparisons of the metabolic components in the lowest quartile and other quartiles of FVC (% pred) among subjects with normal ventilatory function. Table S2. Comparisons of the metabolic components in the lowest quartile and other quartiles of FEV1 (% pred) among subjects with normal ventilatory function. (DOCX 18 kb

Odds ratio for development of diabetes over four years according to baseline insulin resistance, insulin secretion assessed by HOMA index and Lp(a) levels.

<p>Odds ratio for development of diabetes over four years according to baseline insulin resistance, insulin secretion assessed by HOMA index and Lp(a) levels.</p