Omar Yaxmehen Bello-Chavolla

Epidemiology of diabetes mellitus in Mexico

Type 2 diabetes is the main health problem in Mexico. The large and growing number of cases and the remarkable economic impact of the disease support this statement. The condition is expressed at an earlier age and at a lower body mass index in Mexican mestizos compared with the age and body mass index reported in Caucasians. In addition, Mexican mestizos have an increased susceptibility to developing diabetic nephropathy. The Mexican health system needs major adjustments in order to prevent and treat type 2 diabetes. Treatment is not currently based on the needs and expectations of the patient. As a result, it is insufficient, belated, and costly. Close to 20% of the preventable deaths in Mexico are caused by diabetes and related metabolic diseases. Even a small decrease in this rate could result in substantial savings for the Mexican healthcare system.

Mexican Carriers of the HNF1A p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas

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.

METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes

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.

Optimization of kidney dysfunction prediction in diabetic kidney disease using targeted metabolomics

AimsMetabolomics have been used to evaluate the role of small molecules in human disease. However, the cost and complexity of the methodology and interpretation of findings have limited the transference of knowledge to clinical practice. Here, we apply a targeted metabolomics approach using samples blotted in filter paper to develop clinical-metabolomics models to detect kidney dysfunction in diabetic kidney disease (DKD).MethodsWe included healthy controls and subjects with type 2 diabetes (T2D) with and without DKD and investigated the association between metabolite concentrations in blood and urine with eGFR and albuminuria. We also evaluated performance of clinical, biochemical and metabolomic models to improve kidney dysfunction prediction in DKD.ResultsUsing clinical-metabolomics models, we identified associations of decreased eGFR with body mass index (BMI), uric acid and C10:2 levels; albuminuria was associated to years of T2D duration, A1C, uric acid, creatinine, protein intake and serum C0, C10:2 and urinary C12:1 levels. DKD was associated with age, A1C, uric acid, BMI, serum C0, C10:2, C8:1 and urinary C12:1. Inclusion of metabolomics increased the predictive and informative capacity of models composed of clinical variables by decreasing Akaike’s information criterion, and was replicated both in training and validation datasets.ConclusionsTargeted metabolomics using blotted samples in filter paper is a simple, low-cost approach to identify outcomes associated with DKD; the inclusion of metabolomics improves predictive capacity of clinical models to identify kidney dysfunction and DKD-related outcomes.

Diabetes in Latin America

Diabetes has become one of the top causes of death and premature disability in less than half a century in Latin America (LA). Two of the countries with a higher number of affected subjects are located in the region (Brazil and Mexico). Prevalence of the disease is close to 10 % in Latin American countries. Type 2 diabetes explains more than 90 % of cases. Peculiar features of type 2 diabetes in mestizo populations have been identified (early onset of the disease, interaction with infectious diseases, and appearance of hyperglycemia with lower body mass index). Three major challenges exist in the region to mitigate the impact of T2D. First, a large proportion of the population has preceding conditions that increase their risk in the midterm. Second, half of the patients are undiagnosed, precluding the implementation of preventive actions against chronic complications. Third, the effectiveness of treatment programs is below the international standards, resulting in high expenditures without changing the rates of premature disability and mortality. The incidence of end-stage renal disease reported for Mexico is the highest worldwide. This observation is in accordance with the increased susceptibility for having microvascular complications found in Hispanics in the USA. In summary, diabetes is a major health threat in the LA region.