Genetic reanalysis of patients with a difference of sex development carrying the NR5A1/SF-1 variant p.Gly146Ala has discovered other likely disease-causing variations.

NR5A1/SF-1 (Steroidogenic factor-1) variants may cause mild to severe differences of sex development (DSD) or may be found in healthy carriers. The NR5A1/SF-1 c.437G>C/p.Gly146Ala variant is common in individuals with a DSD and has been suggested to act as a susceptibility factor for adrenal disease or cryptorchidism. Since the allele frequency is high in the general population, and the functional testing of the p.Gly146Ala variant revealed inconclusive results, the disease-causing effect of this variant has been questioned. However, a role as a disease modifier is still possible given that oligogenic inheritance has been described in patients with NR5A1/SF-1 variants. Therefore, we performed next generation sequencing (NGS) in 13 DSD individuals harboring the NR5A1/SF-1 p.Gly146Ala variant to search for other DSD-causing variants and clarify the function of this variant for the phenotype of the carriers. Panel and whole-exome sequencing was performed, and data were analyzed with a filtering algorithm for detecting variants in NR5A1- and DSD-related genes. The phenotype of the studied individuals ranged from scrotal hypospadias and ambiguous genitalia in 46,XY DSD to opposite sex in both 46,XY and 46,XX. In nine subjects we identified either a clearly pathogenic DSD gene variant (e.g. in AR) or one to four potentially deleterious variants that likely explain the observed phenotype alone (e.g. in FGFR3, CHD7). Our study shows that most individuals carrying the NR5A1/SF-1 p.Gly146Ala variant, harbor at least one other deleterious gene variant which can explain the DSD phenotype. This finding confirms that the NR5A1/SF-1 p.Gly146Ala variant may not contribute to the pathogenesis of DSD and qualifies as a benign polymorphism. Thus, individuals, in whom the NR5A1/SF-1 p.Gly146Ala gene variant has been identified as the underlying genetic cause for their DSD in the past, should be re-evaluated with a NGS method to reveal the real genetic diagnosis.

Impact of COVID-19 lockdown on glycemic control in patients with type 1 diabetes.

INTRODUCTION: The COVID-19 pandemic has forced governments to take exceptional measures to minimize its spread, imposing lockdown policies. The aim of this study was to evaluate the impact of lockdown on type 1 diabetes (T1D) glycemic control. MATERIAL AND METHODS: People with T1D using flash glucose monitoring were included. Data from the 14 days before lockdown were compared with data from the last 14 days after 8 weeks of lockdown. RESULTS: A total of 307 patients were included (age 45.8 ± 12.6 years, 50.2% male, diabetes duration 21.1 ± 12.3 years). Only one patient had COVID-19 infection. Mean glucose decreased from 166.89 ± 29.4 to 158.0 ± 29.0 mg/dL and estimated HbA1c declined from 7.4 ± 1.0 to 7.1 ± 1.0% (54 ± 10.9 vs 57 ± 10.9 mmol/mol; p < 0.001). Time in range increased from 57.8 ± 15.8 to 62.46 ± 16.1%. Time in hyperglycemia > 180 mg/dL and >250 mg/dL decreased from 37.3 ± 1.9% to 32.0 ± 17.1% and from 13.0 ± 11.3 to 10.3 ± 10.6%, respectively; (p < 0.001). Time in hypoglycaemia <70 mg/dL increased from 4.9 ± 4.0% to 5.5 ± 4.4% (p < 0.001). No differences in time <54 mg/dl, coefficient of variation (CV%) or number of scans per day were found. CONCLUSION: Despite the limitations of lockdown, glycemic control improved in patients with T1D. These results suggest that having more time for self-management may help improve glycemic control in the short term.

Asistencia a la gestante con diabetes. Guía de práctica clínica actualizada en 2014 / Care of pregnancies complicated by diabetes. Clinical practice guidelines: 2014 update

La diabetes es una de las complicaciones metabólicas más frecuentes de la gestación y se asocia a un incremento del riesgo de morbimortalidad maternal y fetal, que pueden evitarse y/o reducirse con un adecuado control. En la diabetes pregestacional, la preparación específica previa a la gestación es indispensable para intentar conseguir un control glucémico lo más próximo a la normalidad, evaluar complicaciones y revisar las pautas de tratamientos farmacológicos. En el caso de la diabetes gestacional, el tratamiento de esta entidad ha demostrado disminuir la tasa de complicaciones maternas y perinatales, por lo que su diagnóstico está justificado. En relación con la estrategia diagnóstica, ante la falta de consenso y la controversia desatada tras la aparición de los nuevos criterios IADPSG, el grupo ha decidido mantener la misma estrategia diagnóstica en 2 pasos y con los mismos puntos de corte hasta disponer de datos sólidos que avalen la introducción de nuevos criterios

Diabetes is one of the most common metabolic complications of pregnancy, and is associated with an increased risk of maternal and foetal morbidity and mortality that can be prevented and/or reduced with adequate glycaemic control. In pre-gestational diabetes, specific preparation prior to the pregnancy is essential in order to achieve glycaemic control near to normal as possible and to evaluate complications and review pharmacologic treatment prescription. The treatment of gestational diabetes has been shown to decrease the rate of maternal and perinatal complications, thus its diagnosis is justified. As regards the diagnostic strategy and due to the lack of consensus and the controversy arising after the publication of the new International Association of the Diabetes and Pregnancy Study Groups (IADPSG), the group has decided to keep the same diagnostic strategy in two stages, and with the same cut-off points, until there are solid data available that support the introduction of new criteria

Diabetes y embarazo. Guía Asistencial 2006 / Diabetes and pregnancy. Clinical guidelines 2006

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