Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India.

Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with HNF1A Ser3Cys, two PDX1 Glu224Lys, His94Gln, two NEUROD1 Glu59Gln, Phe318Ser, one INS Gly44Arg, one GCK, one ABCC8 Arg620Cys and one BLK Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding.

Masked hypoglycemia in pregnancy.

BACKGROUND: Hypoglycemia is a major hindrance for optimal glycemic control in women with gestational diabetes mellitus (GDM) on insulin. In the present study, masked hypoglycemia (glucose <2.77mmol/L for ≥30 min) was estimated in pregnant women using a continuous glucose monitoring (CGM) system. METHODS: Twenty pregnant women with GDM on insulin (cases) and 10 age-matched euglycemic pregnant women (controls) between 24 and 36 weeks gestation were recruited. Both groups performed self-monitoring of blood glucose (SMBG) and underwent CGM for 72 h to assess masked hypoglycemia. Masked hypoglycemic episodes were further stratified into two groups based on interstitial glucose (2.28-2.77 and ≤2.22 mmol/L). RESULTS: Masked hypoglycemia was recorded in 35% (7/20) of cases and 40% (4/10) of controls using CGM, with an average of 1.28 and 1.25 episodes per subject, respectively. Time spent at glucose levels between 2.28 and 2.77 mmol/L did not differ between the two groups (mean 114 vs 90 min; P = 0.617), but cases spent a longer time with glucose ≤2.2 mmol/L. Babies born to women with GDM were significantly lighter than those born to controls (2860 vs 3290 g; P = 0.012). There was no significant difference in birth weight within the groups among babies born to women with or without hypoglycemia. CONCLUSION: Euglycemic pregnant women and those with GDM on insulin had masked hypoglycemia. Masked hypoglycemia was not associated with adverse maternal or fetal outcomes. Therefore, low glucose levels in the hypoglycemic range may represent a physiologic adaptation in pregnancy. This response is exaggerated in women with GDM on insulin.