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Non-cholesterol sterol levels predict hyperglycemia and conversion to type 2 diabetes in Finnish men.

ABSTRACT: We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N?=?1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N?=?273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes.

SUBMITTER: Cederberg H

PROVIDER: S-EPMC3696087 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Non-cholesterol sterol levels predict hyperglycemia and conversion to type 2 diabetes in Finnish men.

Cederberg Henna H Gylling Helena H Miettinen Tatu A TA Paananen Jussi J Vangipurapu Jagadish J Pihlajamäki Jussi J Kuulasmaa Teemu T Stančáková Alena A Smith Ulf U Kuusisto Johanna J Laakso Markku M

PloS one 20130628 6

We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a ...[more]

PMID: 23840693

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Project description:Objective: Fibroblast growth factor 19 (FGF19) plays an indispensable role in regulating bile acid, glucose, and lipid metabolism, and alterations of its circulating concentration is associated with the development of type 2 diabetes (T2D). Atherosclerosis is directly related to the death-deriving diabetic macroangiopathy in T2D, yet relationships between FGF19 and atherosclerosis in T2D remain unclear. The aim of this study was to investigate the association of circulating FGF19 levels with the development of subclinical atherosclerosis (subAS) in patients with T2D in a 3-year prospective study. Methods: In the present study, 153 newly diagnosed T2D patients without subAS were recruited at baseline, and 137 of them completed a 3-year follow-up. FGF19 levels were measured in fasting serum samples collected at baseline and the third-year visits. Carotid, femoral, and iliac intima-media thickness (IMT) were detected by high-resolution B-mode ultrasound to determine the presence of subAS. Logistic regression analysis was applied to assess the relationship between serum FGF19 and subAS in patients with T2D. Results: At baseline, serum FGF19 levels were positively correlated with carotid IMT and iliac IMT in men (r = 0.239, P = 0.036; r = 0.309, P = 0.006). At the 3-year follow-up, 25 out of 153 patients developed subAS, and FGF19 levels in men were higher in the subAS group than in the non-subAS group [202.7 (177.9-373.6) vs. 133.4 (85.6-171.3) pg/ml, P = 0.028]. Furthermore, in men, higher baseline levels of FGF19 were independently associated with a greater risk of subAS at year 3 in patients with T2D with an odds ratio (OR) of 4.798 per 1 standard deviation (SD) of the FGF19 concentration [OR = 4.798 (95% CI, 1.680-13.706), P = 0.003]. Baseline FGF19 levels yielded an area under the receiver operating characteristic curve of 0.769 to predict the development of subAS at year 3 in men with T2D. Conclusions: Serum FGF19 levels could help in predicting the development of atherosclerosis in men with T2D.

Dataset Information

Non-cholesterol sterol levels predict hyperglycemia and conversion to type 2 diabetes in Finnish men.

Publications

Non-cholesterol sterol levels predict hyperglycemia and conversion to type 2 diabetes in Finnish men.

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