Monogenic diabetes due to an INSR mutation in a child with severe insulin resistance

Summary We report a case of an 11-year-old girl presenting with a new diagnosis of diabetes associated with a heterozygous missense mutation in the insulin receptor (INSR) gene. This case highlights that INSR gene variants can be a cause for monogenic diabetes in children and adolescents and the need for genetic evaluation in atypical presentations of diabetes. We also describe the possible role of metformin in treating individuals with type A insulin resistance syndrome due to INSR gene variants. Learning points Insulin receptor (INSR) gene variants can be a cause of monogenic diabetes in children and adolescents. Genetic evaluation should be considered in children and adolescents with type 2 diabetes (T2D), particularly where there is an atypical presentation and/or positive family history. Metformin may have a role in the treatment of type A insulin resistance syndrome due to heterozygous mutation of the INSR gene.

DNA methylation of AMHRII and INSR gene is associated with the pathogenesis of Polycystic Ovary Syndrome (PCOS)

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecologic endocrinopathy, characterized by menstrual disorders, ovulation disorders, polycystic ovary, hyperandrogen syndrome and insulin resistance. At present, the etiology and exact pathogenesis of PCOS are still unclear. Anti-Müllerian hormone is a local regulator secreted by ovarian granulosa cells, and participates in regulating the occurrence and development of PCOS. Insulin resistance is another important pathophysiological feature of PCOS. Although the expression of anti-müllerian hormone receptor (AMHR) and insulin receptor (INSR) in PCOS have been previously reported, the DNA methylation of the genes have not been well characterized. OBJECTIVE: To study AMHR II/INSR and its role in gene methylation in Ovarian and endometrial pathology of PCOS subjects. METHODS: We recruited seventy-five women with PCOS as cases and twenty healthy women as controls, using immunohistochemical method, study localization, distribution and expression of MHRII/INSR in ovary and endometrium and then discover the correlation of AMHRII/INSR gene methylation. RESULTS: Different clinical features in PCOS group AMHRII gene methylation level and insulin resistance relations have significant differences (r= 0.532, P= 0.000); INSR gene methylation level and insulin resistance relations have significant differences (r= 0.281, P= 0.03). CONCLUSIONS: The analysis of DNA methylation suggested that methylation of AMHRII and INSR genes was associated with basic clinical characteristics and insulin resistance of PCOS. These results provide evidence for AMHRII and INSR genes, and their methylation levels are intimately associated with the pathogenesis of PCOS.