T2DM
Dotaz
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- Klíčová slova
- RO-28-1675, GKA 1, GKA 2, GKA 50, LY2121260, PSN-GK1, COMPOUND A, ARRY - 403,
- MeSH
- alosterická regulace účinky léků MeSH
- beta-buňky enzymologie fyziologie účinky léků MeSH
- diabetes mellitus 2. typu farmakoterapie genetika patofyziologie MeSH
- glukokinasa genetika metabolismus účinky léků MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P < 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P < 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population.
- MeSH
- celogenomová asociační studie MeSH
- chronická renální insuficience * genetika patologie MeSH
- diabetes mellitus 2. typu * genetika komplikace MeSH
- diabetické nefropatie * genetika MeSH
- genetická predispozice k nemoci * MeSH
- genetické rizikové skóre MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- progrese nemoci * MeSH
- rizikové faktory MeSH
- senioři MeSH
- sfingosin-N-acyltransferasa genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Ischemická choroba srdeční (ICHS) a ischemická choroba dolních končetin (ICHDK) jsou časté komplikace u pacientů s diabetem druhého typu (T2DM). Jejich včasná předpověď analýzou genetické predisposice by byla klinicky velmi významná. Porovnávali jsme polygenní skóre a výskyt ICHDK a ICHS u českých pacientů s T2DM. Metodika: Z 21 variant, analyzovaných u celkem 1 032 pacientů s T2DM (359 žen a 673 mužů) bylo vybráno 7 (v genech pro FTO, TCF7L2, IRS1, JAZF, ZMIZ, WFS1 a NOTCH2) pro stanovení neváženého polygenního skóre. Protektivní genotyp měl hodnotu 0, genotypy s alespoň jednou rizikovou alelou hodnotu 1. ICHS byla diagnostikována u 35,0 %, ICHDK u 17,5 % pacientů. Výsledky: Pozorovali jsme významný lineární trend výskytu ICHDK (P = 0,0002), ale ne ICHS (P = 0,25) v souvislosti s narůstajícím počtem rizikových alel – polygenní skóre P (pro trend) 0–2 3 4 5 6–7: ICHDK 4,6 % 14,7 % 16,0 % 21,0 % 23,5 %; P = 0,0002 vs ICHS 34,9 % 31,0 % 32,2 % 36,3 % 33,8 %; P = 0,25 ). Jedinci s polygenním skóre 6 a více mají oproti jedincům s hodnotami 0–2 OR (95% CI) pro výskyt ICHDK – 6,3 (1,9–21,3). Závěr: Polygenní skóre může být využito jako nástroj pro detekci jedinců se zvýšeným rizikem ICHDK, ale ne ICHS.
- Publikační typ
- abstrakt z konference MeSH
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
Sodium glucose co-transporter type 2 inhibitors (SGLT-2 inhibitors) are a class of antidiabetics, recently approved for the treatment of patients with T2DM. They feature cardioprotective and renoprotective action, while they exert beneficial effects on metabolic parameters. Non-alcoholic fatty liver disease (NAFLD) is a frequent co-morbidity in diabetic patients. Its prevalence reaches up to 70%. Since there is no specific treatment approved for NAFLD, both experimental and clinical studies have been recently conducted highlighting the efficacy and safety of SGLT-2 inhibitors mainly in animal models and secondarily in patients with T2DM and NAFLD. This class of antidiabetics seems very attractive, improving both glycemic control and liver function tests, while inhibiting NAFLD progression. However, further investigation is required to establish them as a first-line treatment option in T2DM patients with NAFLD, after thorough assessment of their efficacy and safety in clinical practice.
- MeSH
- diabetes mellitus 2. typu komplikace farmakoterapie metabolismus MeSH
- glifloziny MeSH
- glukosa metabolismus MeSH
- hypoglykemika farmakologie MeSH
- jaterní testy metody MeSH
- lidé MeSH
- nealkoholová steatóza jater komplikace farmakoterapie metabolismus MeSH
- transportér 2 pro sodík a glukózu MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- dopisy MeSH
