ContextGenetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM).ObjectiveWe assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy.Methods960 pregnant women (after dropouts 820: case/control: m99’WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m’99WHO criteria based on standard OGTT values.ResultsThe most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m’99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT.ConclusionsWe confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99’WHO and the IADPSG GDM diagnostic criteria.

The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In this post hoc analysis the MTNR1B rs10830963 genotype and the clinical data of 211 Caucasian GDM patients were assessed. As a first step, a pre-pregnancy BMI threshold was determined where the effect of MTNR1B rs10830963/G allele carrying on AIT initiation was the most significant using logistic regression. Maternal age adjusted real-life odds ratios (OR) values were calculated. The chi-square test was also used to calculate the p value and 10.000 bootstrap simulations were performed in each case to re-assess the statistical power and the OR. Carrying the MTNR1B rs10830963/G allele increased the odds of AIT initiation (OR = 5.2, p = 0.02 [χ2 test], statistical power = 0.53) in GDM patients with pre-pregnancy BMI ≥ 29 kg/m2. The statistical power reached 0.77, when the pre-pregnancy BMI cutoff of 27 kg/m2 was used and the genetic effect on AIT initiation was still significant, but only using the logistic regression model. Carrying the MTNR1B rs10830963/G risk allele—in interaction with pre-pregnancy BMI—is likely be considered as a candidate pharmacogenetic marker of antenatal insulin therapy initiation and should be further assessed in precision medicine trials in GDM.

Aim: To investigate the serum circulating DPP4 activity in patients with COVID-19 disease. Materials & methods: Serum samples from 102 hospitalized COVID-19 patients and 43 post-COVID-19 plasma donors and 39 SARS-CoV-2 naive controls and their medical data were used. Circulating DPP4 activities according to different COVID-19 disease peak severity (WHO) groups at sampling and at peak were assessed. Results: A significant decrease (p < 0.0001) in serum DPP4 activity was found in study groups of higher disease severity. When the circulating DPP4 activity was assessed as a prognostic marker, the logistic regression (p = 0.0023) indicated that the enzyme activity is a predictor of mortality (median 9.5 days before death) with receiver operating characteristic area under the curves of 73.33% (p[area = 0.5] <0.0001) as single predictor and 83.45% (p[area = 0.5] <0.0001) in combination with age among hospitalized patients with COVID-19. Conclusion: Decreased circulating DPP4 activity is associated with severe COVID-19 disease and is a strong prognostic biomarker of mortality.

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The non-alcoholic fatty liver disease (NAFLD) as a common metabolic disease affects nearly one third of the population in the developed countries. The significance of the NAFLD is due to its spectrum disease (simple steatosis → NASH [non-alcoholic steatohepatitis] ± fibrosis → cirrhosis → HCC [hepatocellular carcinome]) character; its association with obesity, type 2 diabetes mellitus (T2DM), dyslipidaemia, metabolic syndrome, insulin resistance; and its complications both as a consequence of the direct progression of the liver disease and also related to the additional target organ damage due to the progression of the metabolic disease (cardiovascular, renal). The clinical practice guideline jointly authored by 3 European professional societies (EASL–EASD–EASO) in 2016 offers a gap-filling, more united diagnostic, therapeutical and follow-up algorithm for the management of NAFLD. The authors of this article could only aim at highlighting the most important considerations and cite a few important literatures that became available only after the publication of the original article. Orv Hetil. 2018; 159(45): 1815–1830.