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  • Author: Liliana Muñoz Hernandez x
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Omar Yaxmehen Bello-Chavolla, Paloma Almeda-Valdes, Donaji Gomez-Velasco, Tannia Viveros-Ruiz, Ivette Cruz-Bautista, Alonso Romo-Romo, Daniel Sánchez-Lázaro, Dushan Meza-Oviedo, Arsenio Vargas-Vázquez, Olimpia Arellano Campos, Magdalena del Rocío Sevilla-González, Alexandro J Martagón, Liliana Muñoz Hernández, Roopa Mehta, César Rodolfo Caballeros-Barragán and Carlos A Aguilar-Salinas

Objective

We developed a novel non-insulin-based fasting score to evaluate insulin sensitivity validated against the euglycemic–hyperinsulinemic clamp (EHC). We also evaluated its correlation with ectopic fact accumulation and its capacity to predict incident type 2 diabetes mellitus (T2D).

Design and methods

The discovery sample was composed by 125 subjects (57 without and 68 with T2D) that underwent an EHC. We defined METS-IR as Ln((2*G0)+TG0)*BMI)/(Ln(HDL-c)) (G0: fasting glucose, TG0: fasting triglycerides, BMI: body mass index, HDL-c: high-density lipoprotein cholesterol), and compared its diagnostic performance against the M-value adjusted by fat-free mass (MFFM) obtained by an EHC. METS-IR was validated in a sample with EHC data, a sample with modified frequently sampled intravenous glucose tolerance test (FSIVGTT) data and a large cohort against HOMA-IR. We evaluated the correlation of the score with intrahepatic and intrapancreatic fat measured using magnetic resonance spectroscopy. Subsequently, we evaluated its ability to predict incident T2D cases in a prospective validation cohort of 6144 subjects.

Results

METS-IR demonstrated the better correlation with the MFFM (ρ = −0.622, P < 0.001) and diagnostic performance to detect impaired insulin sensitivity compared to both EHC (AUC: 0.84, 95% CI: 0.78–0.90) and the SI index obtained from the FSIVGTT (AUC: 0.67, 95% CI: 0.53–0.81). METS-IR significantly correlated with intravisceral, intrahepatic and intrapancreatic fat and fasting insulin levels (P < 0.001). After a two-year follow-up, subjects with METS-IR in the highest quartile (>50.39) had the highest adjusted risk to develop T2D (HR: 3.91, 95% CI: 2.25–6.81). Furthermore, subjects with incident T2D had higher baseline METS-IR compared to healthy controls (50.2 ± 10.2 vs 44.7 ± 9.2, P < 0.001).

Conclusion

METS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity.

Restricted access

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.