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Metabolic profiling of tissue-specific insulin resistance in human obesity
- Source :
- International Journal of Obesity, 44, 1376-1386. NATURE PUBLISHING GROUP, International Journal of Obesity, 44(6), 1376-1386. Nature Publishing Group
- Publication Year :
- 2020
-
Abstract
- Background: Recent evidence indicates that insulin resistance (IR) in obesity may develop independently in different organs, representing different etiologies toward type 2 diabetes and other cardiometabolic diseases. The aim of this study was to investigate whether IR in the liver and IR in skeletal muscle are associated with distinct metabolic profiles. Methods: This study includes baseline data from 634 adults with overweight or obesity (BMI ≥ 27 kg/m 2) (≤65 years; 63% women) without diabetes of the European Diogenes Study. Hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), were derived from a five-point OGTT. At baseline 17 serum metabolites were identified and quantified by nuclear-magnetic-resonance spectroscopy. Linear mixed model analyses (adjusting for center, sex, body mass index (BMI), waist-to-hip ratio) were used to associate HIRI and MISI with these metabolites. In an independent sample of 540 participants without diabetes (BMI ≥ 27 kg/m 2; 40–65 years; 46% women) of the Maastricht Study, an observational prospective population-based cohort study, 11 plasma metabolites and a seven-point OGTT were available for validation. Results: Both HIRI and MISI were associated with higher levels of valine, isoleucine, oxo-isovaleric acid, alanine, lactate, and triglycerides, and lower levels of glycine (all p < 0.05). HIRI was also associated with higher levels of leucine, hydroxyisobutyrate, tyrosine, proline, creatine, and n-acetyl and lower levels of acetoacetate and 3-OH-butyrate (all p < 0.05). Except for valine, these results were replicated for all available metabolites in the Maastricht Study. Conclusions: In persons with obesity without diabetes, both liver and muscle IR show a circulating metabolic profile of elevated (branched-chain) amino acids, lactate, and triglycerides, and lower glycine levels, but only liver IR associates with lower ketone body levels and elevated ketogenic amino acids in circulation, suggestive of decreased ketogenesis. This knowledge might enhance developments of more targeted tissue-specific interventions to prevent progression to more severe disease stages.
- Subjects :
- EXPRESSION
medicine.medical_specialty
LIVER
Endocrinology, Diabetes and Metabolism
Population
INDEXES
Medicine (miscellaneous)
030209 endocrinology & metabolism
Type 2 diabetes
DETERMINANTS
Creatine
SERUM
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Insulin resistance
INFLAMMATION
HYPERGLYCEMIA
Diabetes mellitus
Internal medicine
Ketogenesis
medicine
030212 general & internal medicine
education
education.field_of_study
Nutrition and Dietetics
business.industry
MUSCLE
medicine.disease
AMINO-ACID CATABOLISM
BRANCHED-CHAIN
Endocrinology
chemistry
Ketone bodies
business
Body mass index
Subjects
Details
- Language :
- English
- ISSN :
- 03070565
- Volume :
- 44
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- International Journal of Obesity
- Accession number :
- edsair.doi.dedup.....7085ebf27d32361a6137b7d2d9a61044