title: 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.
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Cederberg
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.forename: Tatu A
authors.initials: TA
authors.lastname: Miettinen
authors.forename: Jussi
authors.initials: J
authors.lastname: Paananen
authors.forename: Jagadish
authors.initials: J
authors.lastname: Vangipurapu
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Teemu
authors.initials: T
authors.lastname: Kuulasmaa
authors.forename: Alena
authors.initials: A
authors.lastname: Stančáková
authors.forename: Ulf
authors.initials: U
authors.lastname: Smith
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013261:Sterols / Q000097:blood*
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D001786:Blood Glucose; D013261:Sterols