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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.

Background Lifestyle is the focus of type 2 diabetes (T2D) prevention strategies. Prevention strategies using mobile health (mHealth)–based therapy have shown positive results for T2D prevention in high-income settings, but little is known about their effectiveness in low- and middle-income populations where the burden of T2D is substantial. “Vida Sana” is a web platform designed to record lifestyle habits and medication use within a lifestyle change program. Objective We sought to identify the barriers, feasibility, usability, and effectiveness of Vida Sana to record lifestyle habits in subjects at risk of developing T2D in a middle-income setting. Methods This was a 3-month prospective interventional study in Mexican individuals. A total of 77 subjects at risk of T2D (with prediabetes and BMI between 24 and 40 kg/m2) were selected. Feasibility was assessed by study retention. Usability was evaluated with the System Usability Scale (SUS). Effectiveness measures included changes in weight, body composition, BMI, glycated hemoglobin A1c (HbA1c), and fasting blood glucose from baseline to 3 months. Linear regression models were used to account for covariates. Results The feasibility of Vida Sana was 42%, with 33 subjects using the platform, and the usability was 48.7 (SD 14.24). Reported barriers to platform usage were; difficulty in accessing the platform from difficulty of use (12 subjects, 36%), lack of time to record their habits (11 subjects, 34%), lack of interest to record their habits (6 subjects, 18%), and lack of resources (4 subjects, 11%). The platform was effective for lowering glucose in fasting (–3.1 mg/dL vs –0.11 [SD 8.08] mg/dL; P=.038) and at 2 hours (–16.9 mg/dL vs 2.5 [SD 26.1] mg/dL; P=.045), body fat percentage (–1.3 [–2.2 to –0.7] vs –1.02 [–1.9 to –0.3]; P=.02), and waist circumference (–3.2 [SD 5.1] cm vs –1.7 [SD 5.0] cm; P=.02) independent of their age, sex, treatment, and education level. Conclusions The use of the web platform was effective for improving glycemic and anthropometric parameters in a population at risk of developing diabetes. Improving accessibility and ease of navigation could improve the acceptance of digital health solutions in a middle-income population.

Objective: Osteoporosis is typically identified as a disease of postmenopausal women, however; it has been observed that in patients with type 1 diabetes (T1D) fractures associated with osteoporosis four to six times more common, in both sexes and at an early age (≈ 50 years). The objective of this study was to find associations between the bone mineral density (BMD), T-score and Z-score at the femoral neck, hip and spine and selected characteristics of patients with T1D. Methods: BMD of patients with T1D was evaluated with DXA (GE Healthcare Lunar). A correlation analysis was performed to identify associations between glycated hemoglobin, 25-hydroxyvitamin D concentration, years since diagnosis and diabetic, estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Results: We included 43 patients, with a mean age of 38.1 years, the mean BMD in the femoral neck was 0.94±0.13, in the hip 0.93±0.14 and the spine 1.11±0.13. We observed a negative correlation between the years since diagnosis of T1D and the BMD and T-score in the femoral neck and hip. There was a negative correlation between the ACR and the BMD, T-score and Z-score in the femoral neck and total hip and a positive correlation between the eGFR and the BMD and T-score in the femoral neck and hip. Conclusions: In this study we identify some factors that might impact and decrease the BMD in patients with T1D including long time since diagnosis, older age of patients and presence of diabetic nephropathy. The ACR could be an indicator of early bone metabolic changes in patients with T1D. Further studies are required to confirm this association and to define the optimal age for BMD evaluation in patients with T1D. Disclosure C. Lara: None. F. Rodriguez: None. T. Viveros-Ruiz: None. P. Almeda-Valdes: None. D. Uribe: None. B. Rivas: None. N. Ramirez Pedraza: None. J.A. Garay Mora: None.

Background Postprandial lipemia is an important cardiovascular risk factor. The assessment of postprandial lipid metabolism is a newly trend that several consortiums and countries have adopted. The aim of the study is to determine a postprandial triglyceride concentration cut-off point that accurately discriminate individuals with fasting normal triglyceride concentrations from those with fasting hypertriglyceridemia. Methods Cross sectional population-based study. A total of 212 subjects underwent an eight hours’ oral fat tolerance test. Samples were taken fasting, three, four, five, six and eight hours after the meal. The area under the receiver operating characteristic curve (c-statistic) was computed using postprandial triglycerides concentrations as independent predictor, and fasting hypertriglyceridemia as dependent variable. Results The best threshold of postprandial lipemia to discriminate fasting hypertriglyceridemia was 280 mg/dL at any hour area under the curve 0.816 (95% confidence interval 0.753–0.866), bootstrap-corrected c-statistic = 0.733 (95% confidence interval 0.68–0.86). The same value was compared with apolipoprotein B concentrations (>90th percentile) having a good performance: area under the curve 0.687 95% confidence interval 0.624–0.751). Likewise, subjects with high postprandial lipemia have higher Globo risk scores. Conclusion The 280 mg/dL cut-off point value of postprandial triglycerides concentration any time after a test meal discriminate subjects with fasting hypertriglyceridemia. This threshold has a good performance in a heterogeneous population and has a good concordance with cardiovascular risk surrogates.

OBJECTIVE To assess whether an ethnic-specific variant (p.E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1α (HNF1A) found in Mexicans is associated with higher sensitivity to sulfonylureas, as documented in patients with MODY3. RESEARCH DESIGN AND METHODS We recruited 96 participants (46 variant carriers and 50 age- and sex-matched noncarriers). Response to glipizide (one 2.5–5.0-mg dose), metformin (four 500-mg doses), and an oral glucose challenge was evaluated using a previously validated protocol. Glucose and insulin levels and their areas under the curve (AUCs) were compared between groups. RESULTS Carriers of the p.E508K variant had a lower maximum insulin peak during the glipizide challenge as compared with noncarriers with diabetes (P < 0.05). Also, carriers had a lower insulin response after the oral glucose challenge. Following an oral glucose tolerance test in the presence of metformin, carriers of the p.E508K variant with diabetes had a lower maximum insulin peak and total and incremental insulin AUC value as compared with noncarriers with diabetes (P < 0.05). A similar but nonsignificant trend was seen in participants without type 2 diabetes. CONCLUSIONS Carriers of variant p.E508K in HNF1A have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3.

ObjectiveWe 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 methodsThe 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.ResultsMETS-IR demonstrated the better correlation with the MFFM (ρ = −0.622,P P 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 ConclusionMETS-IR is a novel score to evaluate cardiometabolic risk in healthy and at-risk subjects and a promising tool for screening of insulin sensitivity.

Summary Background & aims Intra-abdominal and visceral fat (VAT) are risk factors for the development of cardio-metabolic comorbidities; however its clinical assessment is limited by technology and required expertise for its assessment. We aimed to develop a novel score (METS-VF) to estimate VAT by combining the non-insulin-based METS-IR index, waist-height ratio (WHtr), age and sex. Methods We developed METS-VF in a sample of 366 individuals with Dual X-ray absorptiometry (DXA). METS-VF was modeled using non-linear regression and validated in two replication cohorts with DXA (n = 184, with n = 118 who also had MRI) and bio-electrical impedance (n = 991). We also assessed METS-VF to predict incident type 2 diabetes (T2D) and arterial hypertension independent of body-mass index (BMI) in our Metabolic Syndrome Cohort (n = 6144). Results We defined METS-VF as: 4.466 + 0.011*(Ln(METS-IR))3 + 3.239*(Ln(WHtr))3 + 0.319*(Sex) + 0.594*(Ln(Age)). METS-VF showed better performance compared to other VAT surrogates using either DXA (AUC 0.896 95% CI 0.847–0.945) or MRI (AUC 0.842 95% CI 0.771–0.913) as gold standards. We identified a METS-VF cut-off point >7.18 in healthy patients which has 100% sensitivity (95% CI 76.8–100) and 87.2% specificity (95% CI 79.1–93.0) to identify increased VAT (>100 cm2). METS-VF also had adequate performance in subjects with metabolically-healthy obesity. Finally, in our metabolic syndrome cohort, subjects in the upper quintiles of METS-VF (>7.2) had 3.8 and 2.0-fold higher risk of incident T2D and hypertension, respectively (p Conclusion METS-VF is a novel surrogate to estimate VAT, which has better performance compared to other surrogate VAT indexes and is predictive of incident T2D and hypertension. METS-VF could be a useful tool to assess cardio-metabolic risk in primary care practice and research settings.