The SLC16A11 risk haplotype is associated with decreased insulin action, higher transaminases and large-size adipocytes.
Eur J Endocrinol
; 180(2): 99-107, 2019 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-30475225
ABSTRACT
Objective A haplotype at chromosome 17p13 that reduces expression and function of the solute carrier transporter SLC16A11 is associated with increased risk for type 2 diabetes in Mexicans. We aim to investigate the detailed metabolic profile of SLC16A11 risk haplotype carriers to identify potential physiological mechanisms explaining the increased type 2 diabetes risk. Design Cross-sectional study. Methods We evaluated carriers (n = 72) and non-carriers (n = 75) of the SLC16A11 risk haplotype, with or without type 2 diabetes. An independent sample of 1069 subjects was used to replicate biochemical findings. The evaluation included euglycemic-hyperinsulinemic clamp, frequently sampled intravenous glucose tolerance test (FSIVGTT), dual-energy X-ray absorptiometry (DXA), MRI and spectroscopy and subcutaneous abdominal adipose tissue biopsies. Results Fat-free mass (FFM)-adjusted M value was lower in carriers of the SLC16A11 risk haplotype after adjusting for age and type 2 diabetes status (ß = -0.164, P = 0.04). Subjects with type 2 diabetes and the risk haplotype demonstrated an increase of 8.76 U/L in alanine aminotransferase (ALT) (P = 0.02) and of 7.34 U/L in gamma-glutamyltransferase (GGT) (P = 0.05) compared with non-carriers and after adjusting for gender, age and ancestry. Among women with the risk haplotype and normal BMI, the adipocyte size was higher (P < 0.001). Conclusions Individuals carrying the SLC16A11 risk haplotype exhibited decreased insulin action. Higher serum ALT and GGT levels were found in carriers with type 2 diabetes, and larger adipocytes in subcutaneous fat in the size distribution in carrier women with normal weight.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Haplótipos
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Resistência à Insulina
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Adipócitos
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Transportadores de Ácidos Monocarboxílicos
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Diabetes Mellitus Tipo 2
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Endocrinol
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article