The persistent hyperinsulinemic hypoglycemia may be caused either by a solitary tumor of the pancreas secreting excessive amount of insulin, known as insulinoma or, rarely, by nesidioblastosis. Nesidioblastosis is a rare cause of persistent hyperinsulinemic hypoglycemia in adults. The incidence of nesidioblastosis in adults is unknown, but it is generally thought to be very low. The β cell changes in adult nesidioblastosis suggest a dysregulation of the function of the cell. The cause of the functional dysregulation in adults is unknown. The pathogenesis of adult nesidioblastosis may be different from infantile congenital hyperinsulinism caused by a genetic effect. Histologically nesidioblastosis is almost always characterized by a proliferation of abnormal β cells throughout the entire pancreas. Clinically and biochemically , it is not possible to distinguish between diffuse nesidioblastosis and insulinoma. If all highly selective noninvasive imaging techiques fail to identify a tumor, selective arterial calcium stimulation testing should be performed. The final diagnosis relies on the histopathologic evaluation. The treatment of adult nesidioblastosis is surgical resection of the pancreas.

Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment. GLP1R rs6923761 (Gly168Ser) and GIPR rs10423928 genotyping was performed using real-time PCR, with subsequent high-resolution melting analysis. The main study outcome was reduction in glycated haemoglobin (HbA1c) after treatment. GLP1R Gly168Ser variant was significantly associated with reduction in HbA1c in an additive model (β = -0.33, p = 0.011). The mean reduction in HbA1c in Ser/Ser homozygotes was significantly lower compared with Gly-allele carriers [0.12 ± 0.23% vs. 0.80 ± 0.09% (1.3 ± 2.5 mmol/mol vs. 8.7 ± 1.0 mmol/mol); p = 0.008]. In conclusion, GLP1R missense variant was associated with a reduced response to gliptin treatment. The genotype-related effect size of ∼0.7% (8 mmol/mol) is equal to an average effect of gliptin treatment and makes this variant a candidate for use in precision medicine.

Aim of this study was to evaluate the effect of vitamin D supplementation in obese, insulin resistant and vitamin D deficient PCOS women on biochemical and clinical hyperandrogenism and menstrual irregularity in comparison to effect of metformin or combined metformin plus vitamin D therapy. Thirty nine PCOS women were randomized into three groups and treated with alfacalcidiol (Group 1), combined alfacalcidiol and metformin therapy (Group 2) and metformin (Group 3) for 6 months. Serum TST, fTST, DHEAS, LH and LH/FSH were measured before and after six months of treatment. Menstrual cycle regularity, hirsutism, acne and pregnancy rate were assessed at the same time. There was a significant decrease in TST levels in the Group 2 and slight but not significant decrease in the Group 3. No significant changes in other parameters (fTST, DHEAS, LH, LH/FSH) have been found after 6 months therapy in all three groups. An improvement of menstrual cycle was detected in 78 % of patients in Group 1 (p<0.04), 80 % in the Group 2 (p<0.03) and in 90 % in the Group 3 (p<0.002), respectively. There was no significant improvement of acne and hirsutism in all three groups (all p not significant). Pregnancy rate was higher in the Group 3 as compared with Groups 1 and 2 (67 % vs. 0 % and 25 %, respectively), however without statistical significance. Vitamin D administration has no significant effect on androgen levels and clinical features of hyperandrogenism in obese vitamin D deficient PCOS women. However, it can potentiate effect of metformin on testosterone levels and LH/FSH ratio but not on clinical hyperandrogenism and pregnancy rate.

Background. Polycystic ovary syndrome (PCOS) is commonly associated with endocrine, metabolic, cardiovascular and other morbidities. However its association with autoimmune diseases is still controversial. Aim. The aim of this study was to assess the prevalence of non organ-specific and antithyroid, antibodies in PCOS women compared to healthy controls. Methods. The study included 152 women with PCOS and 76 healthy controls for the evaluation of non organ-specific autoimmunity and 64 PCOS and 68 controls for the study of organ-specific autoimmunity. All sera were tested for autoantibodies.using the ELISA method.Results. There were no significant differences in the prevalence of ANA, SSA, SSB, anti-dsDNA, anti-RNP, ANCA/MPO or ANCA/PR3 between PCOS and controls. The prevalence of ACLA IgG was higher in controls than PCOS (5.4% v.s. 0%, P=0.011). Patients had a higher prevalence of anti-TPO antibodies (18.75% v.s. 7.35%, P=0.045) and slightly but not significantly higher prevalence of autoimmune thyroiditis (18.75% v.s. 10.29%) than controls. Conclusion. The prevalence of non organ-specific autoantibodies in PCOS women is low and similar to controls. On the other hand, we found a slightly higher prevalence of thyroid autoimmunity in PCOS women.

Polycystic ovary syndrome (PCOS) is commonly associated with a higher cardiometabolic risk. The relationship between steroid hormones and cardiometabolic profile in PCOS has been evaluated, but no single hormonal predictor of this association has been identified to determine. To determine the relationship between steroid hormones and cardiometabolic risk factors in PCOS women. Study included 64 women diagnosed with PCOS. Fasting blood samples were analyzed for biochemical, metabolic parameters and sex steroid hormones. PCOS women with BMI≥27 had significantly higher serum free testosterone (FT), free androgen index (FAI), estrone (E1) (p=0.014, p=0.02, p=0.01) than those with normal weight. In all subjects E1 positively correlated with BMI (p=0.0067), serum insulin (p=0.0046), HOMA-IR (p=0.0125) and negatively with HDL-cholesterol (p=0.009). FAI positively correlated with serum cholesterol (p=0.0457), triacylglycerols (TAG) (p=0.0001), HOMA-IR (p=0.037), and glycemia (p=0.0001), negatively with HDL-cholesterol (p=0.029). In multiple linear regression model E1 most significantly predicted HOMA-IR, whereas FT/FAI predicted HDL-cholesterol and BMI. We conclude that PCOS women with marked overweight or obesity have higher FT, FAI and E1 as compared with nonobese PCOS subjects. E1 and FT may predict worse cardiometabolic profile in PCOS.