Nem alkoholos zsírmájbetegség – a 2016. évi közös EASL–EASD–EASO klinikai ajánlás fényében

Absztrakt: A nem alkoholos zsírmájbetegség (NAFLD) a fejlett országokban a populáció harmadát érintő metabolicus népbetegség. A magas prevalencia mellett a NAFLD jelentőségét a spektrumbetegség (steatosis → NASH [nem alkoholos steatohepatitis] ± fibrosis → cirrhosis → HCC [hepatocellularis carcinoma]) jellege, illetve a társuló kórállapotok (obesitas, 2-es típusú diabetes mellitus, dyslipidaemia, metabolicus szindróma, inzulinrezisztencia), valamint mind a májbetegség közvetlen progressziójából adódó hepaticus, mind a társuló anyagcserezavar progressziójához kapcsolódó célszervkárosodás (cardiovascularis, renalis) adja. A NAFLD diagnosztikus, terápiás, illetve követési algoritmusának egységesebb kialakítására három európai szakmai társaság (EASL–EASD–EASO) összefogásával 2016-ban jelent meg a hiánypótlónak számító klinikai szakmai irányelv. Az eredeti közleményben kiemelt ajánlási pontok szó szerinti fordításra kerülhettek, ugyanakkor az ehhez társuló magyarázó részek – a terjedelmi korlátok miatt – a jelen közleményben nem voltak egy az egyben ismertethetők, így a közlemény szerzői ezekből csak a leglényegesebb szempontok kiemelésére, sőt egy-egy esetben az ajánlás óta megjelent új irodalmak ismertetésére törekedhettek. Orv Hetil. 2018; 159(45): 1815–1830. | Abstract: 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

The MTNR1B rs10830963 Variant in Interaction with Pre-Pregnancy BMI is a Pharmacogenetic Marker for the Initiation of Antenatal Insulin Therapy in Gestational Diabetes Mellitus

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

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 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. RESULTS: The 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. CONCLUSIONS: We 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

Association between maternal gene variants and gestational diabetes mellitus (GDM) using both the International Association of Diabetes and Pregnancy Study Group (IADPSG) and the modified 99' World Health Organization (WHO) GDM diagnostic criteria.

<p>Association between maternal gene variants and gestational diabetes mellitus (GDM) using both the International Association of Diabetes and Pregnancy Study Group (IADPSG) and the modified 99' World Health Organization (WHO) GDM diagnostic criteria.</p