1. The SLC16A11 risk haplotype is associated with decreased insulin action, higher transaminases and large-size adipocytes.
- Author
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Almeda-Valdes P, Gómez Velasco DV, Arellano Campos O, Bello-Chavolla OY, Del Rocío Sevilla-González M, Viveros Ruiz T, Martagón Rosado AJ, Bautista CJ, Muñoz Hernandez L, Cruz-Bautista I, Moreno-Macias H, Huerta-Chagoya A, Rodríguez-Álvarez KG, Walford GA, Jacobs SBR, Guillen Pineda LE, Ordoñez-Sánchez ML, Roldan-Valadez E, Azpiroz J, Furuzawa-Carballeda J, Clark P, Herrera-Hernández MF, Zambrano E, Florez JC, Tusié Luna MT, and Aguilar-Salinas CA
- Subjects
- Alanine Transaminase blood, Body Composition physiology, Body Mass Index, Cell Size, Cross-Sectional Studies, Diabetes Mellitus, Type 2 blood, Female, Genetic Predisposition to Disease, Genotype, Glucose Clamp Technique, Glucose Tolerance Test, Humans, Male, Middle Aged, Subcutaneous Fat metabolism, gamma-Glutamyltransferase blood, Adipocytes cytology, Diabetes Mellitus, Type 2 genetics, Haplotypes, Insulin Resistance genetics, Monocarboxylic Acid Transporters genetics
- 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 (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.
- Published
- 2019
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