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  • Author: Karen Guadalupe Rodríguez-Álvarez x
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Paloma Almeda-Valdes, Donaji V Gómez Velasco, Olimpia Arellano Campos, Omar Yaxmehen Bello-Chavolla, Magdalena del Rocío Sevilla-González, Tannia Viveros Ruiz, Alexandro J Martagón Rosado, Claudia J Bautista, Liliana Muñoz Hernandez, Ivette Cruz-Bautista, Hortensia Moreno-Macias, Alicia Huerta-Chagoya, Karen Guadalupe Rodríguez-Álvarez, Geoffrey A Walford, Suzanne B R Jacobs, Luz E Guillen Pineda, Ma Luisa Ordoñez-Sánchez, Ernesto Roldan-Valadez, Joaquín Azpiroz, Jannette Furuzawa-Carballeda, Patricia Clark, Miguel F Herrera-Hernández, Elena Zambrano, Jose C Florez, María Teresa Tusié Luna and Carlos A Aguilar-Salinas

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 (β = −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.