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

PLoS One. 2013 Jun 28;8(6):e67406. doi: 10.1371/journal.pone.0067406. Print 2013.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • ATP-Binding Cassette Transporters / genetics*
  • Area Under Curve
  • Biomarkers / blood
  • Blood Glucose
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Hyperglycemia / blood*
  • Hyperglycemia / epidemiology
  • Hyperglycemia / genetics
  • Incidence
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Sterols / blood*

Substances

  • ABCG8 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • ATP-Binding Cassette Transporters
  • Biomarkers
  • Blood Glucose
  • Sterols

Grants and funding

This work has been supported by the Academy of Finland (M.L.), the Finnish Diabetes Research Foundation (M.L.), the Finnish Cardiovascular Research Foundation (M.L.), the Strategic Research Funding from the University of Eastern Finland, Kuopio, Finland (M.L.), and EVO grant 5263 from the Kuopio University Hospital (M.L.). The funding bodies named above had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.