Association of Ketone Body Levels With Hyperglycemia and Type 2 Diabetes in 9,398 Finnish Men
Year: 2013
Type: article
Study design: Observational Study
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.
Source: Diabetes
DOI: 10.2337/db12-1363
Authors: Yuvaraj Mahendran, Jagadish Vangipurapu, Henna Cederberg, Alena Stančáková, Jussi Pihlajamäki, Pasi Soininen, Antti J. Kangas, Jussi Paananen, Mete Civelek, Niyas K. Saleem, Päivi Pajukanta, Aldons J. Lusis, Lori L. Bonnycastle, Mario A. Morken, Francis S. Collins, Karen L. Mohlke, Michael Boehnke, Mika Ala-Korpela, Johanna Kuusisto, Markku Laakso
Institutions: University of Eastern Finland, Kuopio University Hospital, University of Oulu, University of California, Los Angeles, National Institutes of Health, National Human Genome Research Institute, University of North Carolina at Chapel Hill, University of Michigan, Oulu University Hospital, University of Bristol
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Itä-Suomen Yliopisto, Academy of Finland, Kuopion Yliopistollinen Sairaala, Oulun Yliopisto, Diabetestutkimussäätiö, National Institutes of Health, Jenny ja Antti Wihurin Rahasto, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1660689499, G1728546362, Targeted Genetic Analysis of T2D and Quantitative Traits, Genetic analysis of type II diabetes in Finnish population, Identifying Genes for Type 2 Diabetes: FUSION, G309065063, Identifying Genes for Type 2 Diabetes: FUSION, Genomics of dyslipidemia in Mexicans, G7197155317, G7410979, Molecular Genetic Approaches in Atherosclerosis Research, G9000061537, Genetic epidemiology of rare and regulatory variants for metabolic traits, Identifying Genes for Type 2 Diabetes: FUSION
OpenAlex ID: W2116945158