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Non-Cholesterol Sterol Levels Predict Hyperglycemia and Conversion to Type 2 Diabetes in Finnish Men

Journal article
Authors H. Cederberg
H. Gylling
T. A. Miettinen
J. Paananen
J. Vangipurapu
J. Pihlajamaki
T. Kuulasmaa
A. Stancakova
Ulf Smith
J. Kuusisto
M. Laakso
Published in Plos One
Volume 8
Issue 6
Pages Article Number: e67406
ISSN 1932-6203
Publication year 2013
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages Article Number: e67406
Language en
Links dx.doi.org/10.1371/journal.pone.006...
Keywords impaired glucose-tolerance, insulin sensitivity, absorption, metabolism, association, obesity, abcg8, dyslipidemia, secretion, diagnosis
Subject categories Diabetology

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.

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