title: Association of ketone body levels with hyperglycemia and type 2 diabetes in 9,398 Finnish men.
abstract: We investigated the association of the levels of ketone bodies (KBs) with hyperglycemia and with 62 genetic risk variants regulating glucose levels or type 2 diabetes in the population-based Metabolic Syndrome in Men (METSIM) study, including 9,398 Finnish men without diabetes or newly diagnosed type 2 diabetes. Increasing fasting and 2-h plasma glucose levels were associated with elevated levels of acetoacetate (AcAc) and β-hydroxybutyrate (BHB). AcAc and BHB predicted an increase in the glucose area under the curve in an oral glucose tolerance test, and AcAc predicted the conversion to type 2 diabetes in a 5-year follow-up of the METSIM cohort. Impaired insulin secretion, but not insulin resistance, explained these findings. Of the 62 single nucleotide polymorphisms associated with the risk of type 2 diabetes or hyperglycemia, the glucose-increasing C allele of GCKR significantly associated with elevated levels of fasting BHB levels. Adipose tissue mRNA expression levels of genes involved in ketolysis were significantly associated with insulin sensitivity (Matsuda index). In conclusion, high levels of KBs predicted subsequent worsening of hyperglycemia, and a common variant of GCKR was significantly associated with BHB levels.
authors.affiliation: Department of Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Yuvaraj
authors.initials: Y
authors.lastname: Mahendran
authors.forename: Jagadish
authors.initials: J
authors.lastname: Vangipurapu
authors.forename: Henna
authors.initials: H
authors.lastname: Cederberg
authors.forename: Alena
authors.initials: A
authors.lastname: Stancáková
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Jussi
authors.initials: J
authors.lastname: Paananen
authors.forename: Mete
authors.initials: M
authors.lastname: Civelek
authors.forename: Niyas K
authors.initials: NK
authors.lastname: Saleem
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Lori L
authors.initials: LL
authors.lastname: Bonnycastle
authors.forename: Mario A
authors.initials: MA
authors.lastname: Morken
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000090:Acetoacetates / Q000097:blood; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005215:Fasting; D005387:Finland / Q000453:epidemiology; D055106:Genome-Wide Association Study; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D007657:Ketone Bodies / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D000090:Acetoacetates; D015415:Biomarkers; D001786:Blood Glucose; D007657:Ketone Bodies; C016635:acetoacetic acid; D020155:3-Hydroxybutyric Acid
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