BackgroundMaturity‐onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY‐X).MethodsWe conducted a next‐generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY‐GCK and 76 were non‐GCK MODY.ResultsAfter excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY‐PDX1/HNF1B.ConclusionA multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY‐X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes.

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Neonatal diabetes mellitus (NDM) is defined as the occurrence of severe hyperglycemia in infants under 6 months old and may be permanent (PNDM) or transient (TNDM).When diabetes is diagnosed at 6-12 months of age (early onset diabetes [EOD]), the etiology may be monogenic; however, most cases consist of type 1 diabetes mellitus (T1DM). Molecular diagnosis was determined in a cohort of 35 unrelated Brazilian patients with NDM or EOD based on targeted next-generation sequencing panel and/or chromosome 6q24 abnormalities. The impact of genetic testing on treatment and follow-up was evaluated. Overall, 24 patients had NDM: with 18 (75.0%) having PNDM, 5 TNDM (20.8%) and 1 case in which this information was unknown. Eleven patients had EOD. Genetic testing was positive in 20/24 patients with NDM (83.3%) and in 18.2% of cases of EOD. The commonest causes were ATP-sensitive potassium (KATP) channel genes, and GCK and IPEX mutations (37.1%, 11.4% and 5.7%, respectively). Patients with PNDM due to KCNJ11 and ABCC8 mutations transitioned successfully to sulfonylureas in almost 60% of cases, reinforcing the benefit of performing genetic testing in NDM as early as possible. This report refers to the largest series of cases of NDM (TNDM and PNDM) and EOD in Brazil in which patients were submitted to molecular investigation and in which the clinical impact of genetic diagnosis was also evaluated.

Background A maturity-onset diabetes of the young (MODY) calculator has been described and validated for use in European Caucasians. This study evaluated its performance in Brazilians diagnosed with diabetes mellitus (DM) before 35 years of age. Methods The electronic records of 391 individuals were reviewed in 2020 at the diabetes clinic of a quaternary hospital in São Paulo were analyzed: 231 with type 1 DM (T1DM), 46 with type 2 (T2DM) and 114 with MODY. The MODY calculator was applied to the three groups. A receiver operating characteristic curve was calculated to obtain cut-off points for this population. Results The principal differences between the MODY and the T1DM and T2DM groups were body mass index, a positive family history of diabetes and mean HbA1c level. Age at diagnosis in the MODY group was only significantly different compared to the T2DM group. Specificity and sensitivity were good for the cut-off points of 40%, 50% and 60%, with the accuracy of the model for any of these cut-off points being > 95%. Conclusion The capacity of the calculator to identify Brazilian patients with MODY was good. Values ≥ 60% proved useful for selecting candidates for MODY genetic testing, with good sensitivity and specificity.

Background and aims: The physiopathology of hyperinsulinemic hypoglycemia (HH) after gastric bypass (GB) is not well understood, although it is a common adverse event after this procedure. The fast absorption of glucose after a meal, the high glucose variability, the increase in glucagon peptide 1 secretion or the hyperplasia of beta cell have been postulated as possible hypothesis. Mixed Meal Tolerance test (MMT) is used in clinical practice during HH investigation, but there is no consensus for HH diagnosis after bariatric surgery. In this scenario, we evaluated the MMT for the diagnosis of HH after GB. Material and Methods: This is an observational cross sectional descriptive study of adult (> 18 years) patients submitted to a MMT after GB from July 2016 to October 2019. 51 patients were divided in two groups: Group 1, with a history of predominantly neuroglycopenic symptoms (n = 24) and Group 2 (control) without symptoms of postprandial hypoglycemia (n= 27). The patients had no diagnosis of diabetes and weren’t using any hypoglycemic drugs. All subjects performed the MMT composed by a typical Brazilian breakfast with the following composition: 494 Kcal with 63.4% carb, 27.5% fat and 9.1% protein, in the morning after 8h fasting and blood samples (glucose, insulin, C peptide) were collected before the meal and every 30 minutes for 5 h after it. A positive test was considered if patient presents Whipple’s Triad: HH (plasma glucose was ≤ 55mg/dL with insulinemia ≥ 3 µU/mL, C peptide ≥ 0.6 ng/mL) and hypoglycemic symptoms. Statistical analysis were done using SPSS 13.0 version. Results:​ From 51 patients, 46 were female, mean age was 46.8 ± 9.2 years. 15 of the 24 patients with predominantly neuroglycopenic symptoms (Group 1) developed laboratory HH, but only 9 (37.5%) presented the Whipple’s Triad. Only one subject of the control group presented HH. All patients with neuroglycopenic symptoms during the test presented HH. From those with HH, 43% presented hypoglycemia at 90’, 50% at 120’ and 6.2% at 150’ during MMT. There were no difference between the two groups when compared the amount of weight loss neither the period of follow up after GB. Conclusion: Since all patients with neuroglycopenic symptoms during the test presented HH it might be a useful tool to exclude HH in patients with hypoglycemic symptoms after GB. This study suggests that the BMT doesn’t need to be 5h, since all of hypoglycemic episodes occur until 150’.