Gestační diabetes mellitus (GDM) představuje dnes poměrně častou komplikaci těhotenství, která má jak bezprostřední dopad na průběh aktuální gravidity a porod, tak pro dlouhodobé metabolické zdraví matky a potomka. Incidence GDM se udává celosvětově okolo 14 %, v České republice 9–24 % v závislosti na použitých kritériích. Preeklampsie (PE) naopak patří mezi spíše vzácnější těhotenské komplikace (incidence celosvětově okolo 2 až 8 %, v České republice 4 až 6%), nicméně její dopad na probíhající těhotenství může být velmi závažný a v minulosti – v podobě eklampsie – dokonce fatální. Cílem tohoto přehledového článku je shrnout současné poznatky o etiopatogenezi obou těhotenských komplikací, tedy (1) GDM a (2) PE. Dále (3) uvést epidemiologická data o izolovaném a současném výskytu GDM a PE a případných úskalích jejich diagnostiky (např. nejednotná kritéria, systém screeningu) a (4) diskutovat případné patofyziologické mechanismy zodpovědné za koincidenci GDM a PE.
Gestational diabetes mellitus (GDM) represents a relatively frequent complication of pregnancy, which has an impact on both the course of the current pregnancy and childbirth, as well as for the long-term metabolic health of the mother and her child. The reported incidence of GDM varies around 14% worldwide (9–24% in the Czech Republic), depending on the diagnostic criteria used. Preeclampsia (PE) is one of the rare pregnancy complications with the incidence about 2–8% worldwide (4–6% in the Czech Republic), but its impact on ongoing pregnancy can be very serious and in the past – in the form of eclampsia – even fatal. The aim of this review article is to summarize the current knowledge of the etiopathogenesis of both pregnancy complications, i.e. (1) GDM and (2) PE. Furthermore, (3) we aim to present the epidemiological data on isolated and parallel occurrence of GDM and PE and the pitfalls of their diagnostics (e.g. inconsistent criteria or screening systems) and (4) to discuss pathophysiological mechanisms responsible for concurrent manifestation of GDM and PE.
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prototypical complex disease with polygenic architecture playing an important role in determining susceptibility to develop the disease (and its complications) in subjects exposed to modifiable lifestyle factors. A current challenge is to quantify the degree of the individual's genetic risk using genetic risk scores (GRS) capturing the results of genome-wide association studies while incorporating possible ethnicity- or population-specific differences. METHODS: This study included three groups of T2DM (T2DM-I, N = 1,032; T2DM-II, N = 353; and T2DM-III, N = 399) patients and 2,481 diabetes-free subjects. The status of the microvascular and macrovascular diabetes complications were known for the T2DM-I patients. Overall, 21 single nucleotide polymorphisms (SNPs) were analyzed, and selected subsets were used to determine the GRS (both weighted - wGRS and unweighted - uGRS) for T2DM risk predictions (6 SNPs) and for predicting the risks of complications (7 SNPs). RESULTS: The strongest T2DM markers (P < 0.0001) were within the genes for TCF7L2 (transcription factor 7-like 2), FTO (fat mass and obesity associated protein) and ARAP1 (ankyrin repeat and PH domain 1). The T2DM-I subjects with uGRS values greater (Odds Ratio, 95 % Confidence Interval) than six had at least twice (2.00, 1.72-2.32) the risk of T2DM development (P < 0.0001), and these results were confirmed in the independent groups (T2DM-II 1.82, 1.45-2.27; T2DM-III 2.63, 2.11-3.27). The wGRS (>0.6) further improved (P < 0.000001) the risk estimations for all three T2DM groups. The uGRS was also a significant predictor of neuropathy (P < 0.0001), nephropathy (P < 0.005) and leg ischemia (P < 0.0005). CONCLUSIONS: If carefully selected and specified, GRS, both weighted and unweighted, could be significant predictors of T2DM development, as well as the diabetes complications development.
- MeSH
- celogenomová asociační studie MeSH
- diabetes mellitus 2. typu * komplikace genetika MeSH
- gen pro FTO genetika MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- komplikace diabetu * MeSH
- lidé MeSH
- rizikové faktory MeSH
- T-buňky - transkripční faktor 1 genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Gestational diabetes mellitus (GDM) represents a risk factor for both mother and her offspring in a short-term (perinatal morbidity) and long-term horizon (postpartum diabetes or foetal programming). Several studies focused at peri/postnatal outcomes of GDM mother ́s offspring, however relatively few (and none in Czech population) were designed as prospective. The aim of the study was to ascertain eventual anthropometric and developmental abnormalities and/or morbidity in offspring of GDM mothers compare to controls in a 5-year follow-up using a parent-reported parameters related to psychomotor development and common paediatric morbidities including a sub-study of offspring of GDM mothers experiencing adverse perinatal outcomes. METHODS: A 5 year follow up study of offspring of GDM mothers (n = 26) vs those with a normal pregnancy (n = 63). An electronic questionnaire was used to obtain the parameters (such as growth, psychomotor development, vaccination, morbidity history etc.) available to parents from the parent-held infant health record. Data on pregnancy and delivery were available from the previous study. RESULTS: Offspring of GDM mothers had delayed psychomotor development in early childhood, but in 5 years of age they seemed to gradually achieve results of a control group. Children with macrosomia had a higher percentile of weight-for-height and were significantly more frequently ill than those with a normal birth weight. Offspring of obese mothers had worse verbal language skills in early childhood and a higher percentile of weight-for-height. CONCLUSION: Maternal gestational diabetes and obesity can be considered an important determinant of postnatal offspring development and health status, which further advocates for broader implementation of preventive strategies.
- MeSH
- dítě MeSH
- gestační diabetes * MeSH
- index tělesné hmotnosti MeSH
- kojenec MeSH
- lidé MeSH
- morbidita MeSH
- následné studie MeSH
- obezita epidemiologie MeSH
- porodní hmotnost MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case-control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications. METHODS AND RESULTS: APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N = 1274; N = 829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR-RFLP in healthy nondiabetic controls (N = 2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI] = 0.88 [0.71-1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI] = 0.65 [0.42-0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI] = 0.50 [0.25-0.99]); and remains significant (P = 0.044) after adjustment for diabetes duration and BMI. CONCLUSION: Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.
- MeSH
- alely MeSH
- apolipoprotein E4 genetika metabolismus MeSH
- apolipoproteiny E genetika metabolismus MeSH
- diabetes mellitus 2. typu genetika metabolismus MeSH
- diabetická retinopatie genetika metabolismus MeSH
- dospělí MeSH
- frekvence genu genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
