Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case-Control Study.

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012−2014 and 2018−2021. We conducted a case−control study (including 318 pregnant women) nested on two previous studies. In 2012−2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th−14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th−32nd week of gestation. In the period of 2018−2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th−32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1−25.7] vs. 20.5 [14.5−27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8−33.0] vs. 26.7 [20.8−36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018−2021 compared to 2012−2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012−2014 and 2018−2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018−2021 did not lead to higher levels of 25(OH)D.

Case Report: COVID-19-Associated ROHHAD-Like Syndrome.

It is known that the SARS-CoV-2 virus may cause neurologic damage. Rapid-onset obesity, hypoventilation, hypothalamus dysfunction, and autonomic dysregulation (ROHHAD) syndrome is a disease of unknown etiology with a progressive course and unclear outcomes. The etiology of ROHHAD syndrome includes genetic, epigenetic, paraneoplastic, and immune-mediated theories, but to our knowledge, viral-associated cases of the disease have not been described yet. Here we present the case of a 4-year-old girl who developed a ROHHAD syndrome-like phenotype after a COVID-19 infection and the results of 5 months of therapy. She had COVID-19 pneumonia, followed by electrolyte disturbances (hypernatremia and hyperchloremia), hypocorticism and hypothyroidism, central hypoventilation-requiring prolonged assisted lung ventilation-bulimia, and progressive obesity with hypertriglyceridemia, dyslipidemia, hyperuricemia, and hyperinsulinemia. The repeated MRI of the brain and hypothalamic-pituitary region with contrast enhancement showed mild post-hypoxic changes. Prader-Willi/Angelman syndrome as well as PHOX2B-associated variants was ruled out. Treatment with non-steroidal anti-inflammatory drugs and monthly courses of intravenous immunoglobulin led to a dramatic improvement. Herein the first description of ROHHAD-like syndrome is timely associated with a previous COVID-19 infection with possible primarily viral or immune-mediated hypothalamic involvement.

Case Report: A novel PHOX2B p.Ala248_Ala266dup variant causing congenital central hypoventilation syndrome.

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by central alveolar hypoventilation and impaired autonomic regulation, caused by pathogenic variants of PHOX2B gene. More than 90% of patients have a polyalanine repeat mutation (PARM) in the heterozygous state, characterized by the expansion of GCN repeats and an increase in the number of alanine repeats, so that genotypes 20/24-20/33 are formed (the normal genotype is 20/20). The remaining 10% of patients harbor non-PARMs. Case description: We present a clinical case of a girl with a novel PHOX2B heterozygous genetic variant in the exon 3: NM_003924.4: c.735_791dup, p.Ala248_Ala266dup. The duplication includes 16 GCN (alanine) repeats and 3 adjacent amino acids. Both clinically healthy parents demonstrated a normal PHOX2B sequence. In addition, the girl has a variant of unknown significance in RYR1 gene and a variant of unknown significance in NKX2-5 gene. The child's phenotype is quite special. She needs ventilation during sleep, and has Hirschsprung's disease type I, arteriovenous malformation S4 of the left lung, ventricular and atrium septal defects, coronary right ventricular fistula, hemodynamically nonsignificant, episodes of sick sinus and atrioventricular dissociation with bradycardia, divergent alternating strabismus, and oculus uterque (both eyes) (OU) retinal angiopathy. Two episodes of hypoglycemic seizures were also registered. Severe pulmonary hypertension resolved after appropriate ventilation adjustment. Diagnostic odyssey was quite dramatic. Conclusion: Detection of a novel PHOX2B variant expands the understanding of molecular mechanisms of CCHS and genotype-phenotype correlations.

Association of Common Genetic Risk Variants With Gestational Diabetes Mellitus and Their Role in GDM Prediction.

Objective: We aimed to explore the associations between common genetic risk variants with gestational diabetes mellitus (GDM) risk in Russian women and to assess their utility in the identification of GDM cases. Methods: We conducted a case-control study including 1,142 pregnant women (688 GDM cases and 454 controls) enrolled at Almazov National Medical Research Centre. The International Association of Diabetes and Pregnancy Study Groups criteria were used to diagnose GDM. A total of 11 single- nucleotide polymorphisms (SNPs), including those in HKDC1 (rs10762264), GCK (rs1799884), MTNR1B (rs10830963 and rs1387153), TCF7L2 (rs7903146 and rs12255372), KCNJ11 (rs5219), IGF2BP2 (rs4402960), IRS1 (rs1801278), FTO (rs9939609), and CDKAL1 (rs7754840) were genotyped using Taqman assays. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). A simple-count genetic risk score (GRS) was calculated using 6 SNPs. The area under the receiver operating characteristic curve (c-statistic) was calculated for the logistic regression model predicting the risk of GDM using clinical covariates, SNPs that had shown a significant association with GDM in our study, GRS, and their combinations. Results: Two variants in MTNR1B (rs1387153 and rs10830963) demonstrated a significant association with an increased risk of GDM. The association remained significant after adjustment for age, pre-gestational BMI, arterial hypertension, GDM in history, impaired glucose tolerance, polycystic ovary syndrome, family history of diabetes, and parity (P = 0.001 and P < 0.001, respectively). After being conditioned by each other, the effect of rs1387153 on GDM predisposition weakened while the effect of rs10830963 remained significant (P = 0.004). The risk of GDM was predicted by clinical variables (c-statistic 0.712, 95 % CI: 0.675 - 0.749), and the accuracy of prediction was modestly improved by adding GRS to the model (0.719, 95 % CI 0.682 - 0.755), and more by adding only rs10830963 (0.729, 95 % CI 0.693 - 0.764). Conclusion: Among 11 SNPs associated with T2D and/or GDM in other populations, we confirmed significant association with GDM for two variants in MTNR1B in Russian women. However, these variants showed limited value in the identification of GDM cases.