A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus.

AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. RESULTS: There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was -6.57 ± 7.34 mg/ml (p = 0.04). CONCLUSIONS: A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

Basic and Meal Stimulated Plasma GIP Levels are Higher in Lean PCOS Women with FAI over 5.

OBJECTIVE: Glucose dependent insulinotropic peptide (GIP) belongs to the incretins which are responsible for 70% of the insulin release after oral glucose intake. Its impaired secretion was noted in several conditions involving insulin resistance, including polycystic ovary syndrome (PCOS), known as the state with increased testosterone level. This paper considers a possible relationship between the free androgen index (FAI) and basal as well as meal stimulated level of GIP in lean women affected by PCOS. To our knowledge, no previous study has evaluated the matter so far. DESIGN: cross-sectional study METHODS: 50 age-matched lean women (BMI=20.76±1.83) were enrolled to the study and divided into 2 groups. Patients with phenotype with FAI<5 were classified as group 1, PCOS patients with FAI>5 formed group 2. All subjects underwent standard meal test. Serum GIP concentration was determined both at fasting and at 60 min of the test. Calculations were carried out using Statistica 10. RESULTS: Mann-Whitney test indicated a statistically significant difference in medians values of GIP plasma levels between groups on fasting (36.4 pg/ml vs. 59.6 pg/ml; p=0.0007) and at 60 min after meal test (50.1 pg/ml vs. 72.5 pg/ml; p=0.006). Spearman test indicated significant positive correlation between FAI and GIP levels at 0' and 60' in total study population (0':R=0.37;p=0.008; 60':R=0.28; p=0.049). CONCLUSION: Excess androgen activity might be a factor contributing to alter secretion of incretins in lean PCOS women. However it could not be ruled out that it is also possible that increased GIP levels might induce hyperandrogenemia in PCOS. An increased GIP levels may induce hyperinsulinemia and play an additive to insulin resistance role in progression to diabetes mellitus type 2 (DMT2).