Anti-Müllerian hormone and inhibin B levels as markers of premature ovarian aging and transition to menopause in type 1 diabetes mellitus

BACKGROUNDSerum anti-Müllerian hormone (AMH) levels decrease early during the transition to menopause and women with type 1 diabetes mellitus (DM1) experience menopause at a younger age. We hypothesized that older women with DM1 will have lower AMH levels than controls.METHODSWe studied ovarian function in women with DM1 (n = 66) and healthy controls (n = 58), all 33 years (4.1 ± 4.2 versus 9.5 ± 7.9 pmol/l, mean ± SD, P = 0.006). A higher proportion of women with DM1 showed AMH levels in the menopausal range compared with controls (16.7 versus 3.4, respectively, P = 0.02). For all patients, those with DM1 exhibited lower inhibin B levels than controls (89.3 ± 51.7 versus 113.2 ± 76.0 ng/ml, P < 0.05). FSH and estradiol were similar in both groups. Regression analysis showed an earlier decline in AMH levels in women with DM1 than controls. Even after age adjustment, DM1 was a significant factor for the determination of inhibin B and AMH levels.CONCLUSIONSLower AMH levels in women with DM1 during the fourth decade of life suggest the presence of an earlier decline in the ovarian follicle pool in these women. Further studies are needed to evaluate the mechanism of this complication.Fil: Soto, Néstor. San Borja Arriarán Clinical Hospital; ChileFil: Iñiguez, Germán. Universidad de Chile; ChileFil: López, Patricia. Universidad de Chile; ChileFil: Larenas, Gladys. Universidad de La Frontera; ChileFil: Mujica, Verónica. Hospital Regional de Talca; Chile. Universidad de Talca; ChileFil: Rey, Rodolfo Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Codner, Ethel. Universidad de Chile; Chil

Permanent Neonatal Diabetes and Enteric Anendocrinosis Associated With Biallelic Mutations in NEUROG3

Artículo de publicación ISIOBJECTIVE—NEUROG3 plays a central role in the development of both pancreatic islets and enteroendocrine cells. Homozygous hypomorphic missense mutations in NEUROG3 have been recently associated with a rare form of congenital malabsorptive diarrhea secondary to enteroendocrine cell dysgenesis. Interestingly, the patients did not develop neonatal diabetes but childhood-onset diabetes. We hypothesized that null mutations in NEUROG3 might be responsible for the disease in a patient with permanent neonatal diabetes and severe congenital malabsorptive diarrhea. RESEARCH DESIGN AND METHODS—The single coding exon of NEUROG3 was amplified and sequenced from genomic DNA. The mutant protein isoforms were functionally characterized by measuring their ability to bind to an E-box element in the NEUROD1 promoter in vitro and to induce ectopic endocrine cell formation and cell delamination after in ovo chicken endoderm electroporation. RESULTS—Two different heterozygous point mutations in NEUROG3 were identified in the proband [c.82G.T (p.E28X) and c.404T.C (p.L135P)], each being inherited from an unaffected parent. Both in vitro and in vivo functional studies indicated that the mutant isoforms are biologically inactive. In keeping with this, no enteroendocrine cells were detected in intestinal biopsy samples from the patient. CONCLUSIONS—Severe deficiency of neurogenin 3 causes a rare novel subtype of permanent neonatal diabetes. This finding confirms the essential role of NEUROG3 in islet development and function in humans

Estrogen and type 1 diabetes mellitus

Patients with type 1 diabetes mellitus (T1DM) face an array of difficulties during puberty which tend to be more significant in females. Excessive weight and fat mass gain, deterioration of metabolic control, loss of height gain and delays in pubertal development may complicate adolescence in girls with T1DM. Hypogonadotropic hypogonadism, hypoestrogenism, menstrual irregularities, polycystic ovaries and early menopause have also been described to T1DM women. In spite of the beneficial effects of estrogen with regard to insulin action and secretion In healthy women, it is striking that women with T1DM seem to lose these beneficial metabolic effects of estrogen. Some of the problems observed in T1DM women may in part be due to the relationship between decreased estrogen levels and insulin action. This article reviews the effects of estrogen on insulin sensitivity and secretion in non-diabetic women, as well as estrogen physiology in T1DM women

Premature thelarche from phenotype to genotype

Premature thelarche is a benign condition, which has been described as a "variant of puberty". Early breast development is especially prevalent during the first year of life, when the gonadal axis is usually active. Ultrasensitive bioassays have described higher estrogen levels in these girls compared to controls. Some cases of premature thelarche may also exhibit increased growth velocity and/or bone age, despite prepubertal gonadotropin secretion. These cases have been labeled as exaggerated thelarche and may represent an intermediate state between benign premature thelarche and precocious puberty. Several factors have been associated with the etiology of premature thelarche, such as endocrine disruptors, and genetic and nutritional factors. Recently, it has been shown that some girls with exaggerated or fluctuating thelarche may have an activating mutation in the CNAS gene, which codifies for a subunit of G stimulating protein (Gsα). We discuss the different phenotypes that may be