Metabolites include amino acids, intermediates in glucose synthesis, ketone bodies, and fatty acids
MONDAY, April 23 (HealthDay News) — Twenty metabolites, including amino acids, intermediates in glucose synthesis, ketone bodies, and fatty acids, are associated with insulin resistance, according to a study published online April 17 in Diabetes.
Peter Würtz, Ph.D., from the University of Oulu in Finland, and colleagues performed metabolic profiling using high-throughput nuclear magnetic resonance spectroscopy in 7,098 Finns (mean age, 31 years; 52 percent women).
The researchers identified 20 metabolites that were significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR). These included branched-chain and aromatic amino acids, intermediates in gluconeogenesis, ketone bodies, and fatty acid composition and saturation. Associations for amino acids Leu, Ile, Val, and Tyr were sex- and obesity-dependent, with significant associations only seen in abdominally obese women. Protein energy intake was associated with some amino acids (Val, Phe, Tyr, and Gln) but not with the insulin resistance index. One of 12 genetic determinants of HOMA-IR, a variant in GCKR, was significantly associated with 12 metabolites.
”Metabolic signatures extending beyond obesity and lipid abnormalities reflected the degree of insulin resistance evidenced in young, normoglycemic adults with sex-specific fingerprints,” Würtz and colleagues conclude.
Abstract
Metabolic Signatures of Insulin Resistance in 7,098 Young Adults
Peter Würtz1,2,3⇓,
Ville-Petteri Mäkinen1,4,5,
Pasi Soininen1,6,
Antti J. Kangas1,
Taru Tukiainen1,2,
Johannes Kettunen2,7,
Markku J. Savolainen1,8,
Tuija Tammelin9,
Jorma S. Viikari10,
Tapani Rönnemaa10,
Mika Kähönen11,
Terho Lehtimäki12,
Samuli Ripatti2,7,13,
Olli T. Raitakari14,15,
Marjo-Riitta Järvelin3,16,17,18 and
Mika Ala-Korpela1,6,8⇓
+ Author Affiliations
1Computational Medicine Research Group, Institute of Clinical Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland
2Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
3Department of Epidemiology and Biostatistics, Imperial College London, London, U.K.
4Folkhälsan Research Center, University of Helsinki, Helsinki, Finland
5Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
6NMR Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, Finland
7Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
8Department of Internal Medicine, Clinical Research Center, Biocenter Oulu, University of Oulu, Oulu, Finland
9LIKES Research Center for Sport and Health Sciences, Jyväskylä, Finland
10Department of Medicine, Turku University Hospital, University of Turku, Turku, Finland
11Department of Clinical Physiology, Tampere University Hospital, University of Tampere, Tampere, Finland
12Department of Clinical Chemistry, Tampere University Hospital, University of Tampere, Tampere, Finland
13Wellcome Trust Sanger Institute, Hinxton, U.K.
14Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
15Department of Clinical Physiology, Turku University Hospital, University of Turku, Turku, Finland
16Department of Children, Young People, and Families, National Institute for Health and Welfare, Helsinki, Finland
17Institute of Health Sciences, Biocenter Oulu, University of Oulu, Oulu, Finland
18Medical Research Council Health Protection Agency, Centre for Environment and Health, Imperial College London, London, U.K.
Corresponding authors: Peter Würtz, peter.wyrtz@computationalmedicine.fi, and Mika Ala-Korpela, mika.ala-korpela@computationalmedicine.fi.
Abstract
Metabolite associations with insulin resistance were studied in 7,098 young Finns (age 31 ± 3 years; 52% women) to elucidate underlying metabolic pathways. Insulin resistance was assessed by the homeostasis model (HOMA-IR) and circulating metabolites quantified by high-throughput nuclear magnetic resonance spectroscopy in two population-based cohorts. Associations were analyzed using regression models adjusted for age, waist, and standard lipids. Branched-chain and aromatic amino acids, gluconeogenesis intermediates, ketone bodies, and fatty acid composition and saturation were associated with HOMA-IR (P < 0.0005 for 20 metabolite measures). Leu, Ile, Val, and Tyr displayed sex- and obesity-dependent interactions, with associations being significant for women only if they were abdominally obese. Origins of fasting metabolite levels were studied with dietary and physical activity data. Here, protein energy intake was associated with Val, Phe, Tyr, and Gln but not insulin resistance index. We further tested if 12 genetic variants regulating the metabolites also contributed to insulin resistance. The genetic determinants of metabolite levels were not associated with HOMA-IR, with the exception of a variant in GCKR associated with 12 metabolites, including amino acids (P < 0.0005). Nonetheless, metabolic signatures extending beyond obesity and lipid abnormalities reflected the degree of insulin resistance evidenced in young, normoglycemic adults with sex-specific fingerprints.
Diabetes
From ADA
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