OBJECTIVE: Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS: In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin.RESULTS: The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06–1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = −0.05 [−0.06 to −0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35–2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12–1.70).CONCLUSIONS: Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.

Epigenetic markers are potential biomarkers for diabetes and related complications. Using a prospective cohort from the Hong Kong Diabetes Register, we perform two independent epigenome-wide association studies to identify methylation markers associated with baseline estimated glomerular filtration rate (eGFR) and subsequent decline in kidney function (eGFR slope), respectively, in 1,271 type 2 diabetes subjects. Here we show 40 (30 previously unidentified) and eight (all previously unidentified) CpG sites individually reach epigenome-wide significance for baseline eGFR and eGFR slope, respectively. We also develop a multisite analysis method, which selects 64 and 37 CpG sites for baseline eGFR and eGFR slope, respectively. These models are validated in an independent cohort of Native Americans with type 2 diabetes. Our identified CpG sites are near genes enriched for functional roles in kidney diseases, and some show association with renal damage. This study highlights the potential of methylation markers in risk stratification of kidney disease among type 2 diabetes individuals.

Background: To investigate the expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in renal ischemia-reperfusion injury and explore its role in acute kidney injury. Methods: 18 mice were randomly divided into a sham operation group (Sham) and an ischemia-reperfusion group (IR) in which animals were sacrificed at 6 h or 12 h after surgery. The kidneys were harvested to measure the expression of MALAT1 mRNA. HK2 cells were treated with cobalt chloride (CoCl₂) to mimic hypoxia or transfected with siRNA to knockdown MALAT1 before CoCl₂ treatment. After that, MALAT1 was analyzed by RT-PCR (reverse transcription-polymerase chain reaction). HIF-1ɑ (hypoxia-inducible factor-1 alpha) and NF-κB (nuclear factor-kappa B) was measured by Western blot. The concentrations of IL-6 (interleukin-6) and TNF-ɑ (tumor necrosis factor-alpha) in the media were detected by ELISA (enzyme-linked immunosorbent assay). Results: The expression of MALAT1 in the IR (6 h/12 h) group was significantly higher than that in the sham group. In HK2 cells, MALAT1 was significantly increased at 1 h, 3 h, and 6 h after CoCl₂ treatment but had reduced to the basal level at 12 h and 24 h. Knockdown of MALAT1 by siRNA significantly up-regulated the expression of HIF-1ɑ and NF-κB proteins in CoCl₂-treated HK2 cells. In addition, the concentrations of IL-6 and TNF-ɑ were increased by MALAT1 siRNA transfection in CoCl₂-treated HK2 cells. Conclusion: The expression of MALAT1 is increased in renal ischemia-reperfusion injury. It is likely that MALAT1 inhibits the hypoxia-induced inflammatory response through the NF-κB pathway.

To assess the efficacy and safety of double J (DJ) stented, external stented and stent-less procedures in pediatric pyeloplasty by adopting a network meta-analysis (NMA). Electronic databases including PubMed, Cochrane Library, Web of science and Embase database were retrieved. The trials that compared double J (DJ) stented, external stented or stent-less procedures in pediatric pyeloplasty were identified. A network meta-analysis was conducted with the software of STATA 14.0. Probability-based ranking results were performed to identify the best treatment, and publication bias was analyzed by funnel plots. 15 studies with 1731 participants were enrolled in the analysis, including 4 randomized controlled trials (RCT) and 11 retrospective studies. The NMA results revealed that no significant differences were detected in the outcomes of operative time, operative success, hospital stay, improvement of renal functions, overall complications and redo pyeloplasty. DJ stented and external stented procedures were associated with more postoperative pain than that of stent-less procedures [DJ stented: OR = 4.47, 95%CI(1.05,19.08); external stented: OR = 5.83, 95%CI(0.09,1.43)]. DJ stented procedure had a lower rate of urine leakage than those of external stented procedure [OR = 0.18, 95%CI (0.04, 0.76)] and stent-less procedure [OR = 0.07, 95%CI=(0.01, 0.34)]. No significant difference was observed in other types of complications such as urinary tract infection (UTI), stent migration, recurrent ureteropelvic junction obstruction (UPJO) and fever. The probabilities of ranking results indicated that the DJ stented procedure was the best treatment in the outcomes of hospital stay, operative success, improvement of renal functions, and the complication of urine leakage. Stent-less procedure showed its advantages in the outcomes of operative time, flank pain and UTI. External stented procedure had the lowest rate of overall complications and redo pyeloplasty. There were no obvious differences in operative time, operative success, hospital stay, improvement of renal functions, overall complications between external stented, DJ stented and stent-less procedures for pediatric pyeloplasty. When considering the ranking results, the DJ stented procedure seemed to be more beneficial for pediatric pyeloplasty than the other methods. However, with the limitation of our study, additional high-quality studies are needed for further evaluation.

Long non-coding RNA (lncRNA) is a kind of non-coding RNA with transcripts more than 200 bp in length. LncRNA can interact with the miRNA as a competing endogenous RNA (ceRNA) to regulate the expression of target genes, which play a significa...

Papillary renal cell carcinoma (PRCC) is the second most common subtype of renal cell carcinoma, and it lacks effective therapeutic targets and prognostic molecular biomarkers. Attention has been increasingly focused on long noncoding RNAs (lncRNAs), which can act as competing endogenous RNA (ceRNA) to compete for shared microRNAs (miRNAs) in the tumorigenesis of human tumors. Therefore, to clarify the functional roles of lncRNAs with respect to the mediated ceRNA network in PRCC, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 289 PRCC tissues and 32 normal tissues in The Cancer Genome Atlas. As a result, we identified 2,197 differentially expressed mRNAs (DEmRNAs) and 84 differentially expressed miRNAs (DEmiRNAs) using a threshold of |log2 (fold change)| >2.0 and an adjusted P-value <0.05. To determine the hub DEmRNAs that could be key target genes, a weighted gene co-expression network analysis was performed. A total of 28 hub DEmRNAs were identified as potential target genes. Seven dysregulated DEmiRNAs were identified that were significantly associated with the 28 hub potential target genes. In addition, we found that 16 differentially expressed lncRNAs were able to interact with the DEmiRNAs. Finally, we used Cytoscape software to visualize the ceRNA network with these differently expressed molecules. From these results, we believe that the identified ceRNA network plays a crucial role in the process of PRCC deterioration, and some of the identified genes are strongly related to clinical prognosis.