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Diabetic nephropathy (DN) is a major complication in diabetic patients. Microalbuminuria testing is used to identify renal disease; however, its predictive value is questionable. We aimed to identify urinary biomarkers to early diagnosis nephropathy before identifiable alternations in kidney function or urine albumin excretion occurs. Proteomic approaches were used to identify potential urinary biomarkers and enzyme-linked immunosorbent assay was performed to verify the results. The data identified haptoglobin (HPT) and α-1-microglobulin/bikunin precursor (AMBP) as two biomarkers with the highest ability to distinguish between healthy individuals and patients with nephropathy, and between diabetic patients with and without DN. Further, the HPT-to-creatinine ratio (HCR) was evaluated as an independent predictor of early renal functional decline (ERFD) in a cohort with an average follow-up of 4.2 years. The area under the curve (AUC) value for ERFD prediction was significantly improved when the HCR biomarker was included in the model with albumin to creatinine ratio (ACR) and baseline characteristics (AUC values were 0.803 and 0.759 for HCR and ACR, respectively; p value was 0.0423 for difference between models). In conclusion, our results suggest that HCR represents an early indicator of nephropathy, and a marker related to ERFD among diabetic patients in Taiwan. [ABSTRACT FROM AUTHOR]

Adiponectin (APN) is suggested to be a potential biomarker for predicting diabetic retinopathy (DR) risk, but the association between APN and DR has been inconsistent in observational studies. We used a Mendelian randomization (MR) analysis to evaluate if circulating APN levels result in DR. We applied three different genetic risk scores (GRS): GRS All combined all 47 single nucleotide polymorphisms (SNPs), which from a genome-wide association study (GWAS) database-catalog reach significance level; GRS Limited comprised 16 GRS All -SNPs with a rigorous threshold ( p < 5.0 × 10 -8 for GWAS), and GRS APN combined 5 SNPs significantly associated with APN level. The MR-inverse-variance weighted method analysis showed that for each 1-SD increase in genetically induced increase in plasma APN, the OR of having DR was β = 0.20 (95% CI: -0.46-0.85, p = 0.553) for GRS APN , 0.61 (95% CI: 0.10-1.13, p = 0.020) for GRS All , and 0.57 (95% CI: -0.06 to 1.20, p = 0.078) for GRS Limited . Sensitivity analysis, including MR-egger regression and the weighted-median approach, did not provide evidence of the pleiotropic effect of IVs. Limited evidence for the causal role of APN in DR risk among Taiwanese diabetic patients was shown based on MR analysis in the present study.

Objective: Diabetic nephropathy (DN) and diabetic retinopathy (DR) comprise major microvascular complications of diabetes that occur with a high concordance rate in patients and are considered to potentially share pathogeneses. In this case-control study, we sought to investigate whether DR-related single nucleotide polymorphisms (SNPs) exert pleiotropic effects on renal function outcomes among patients with diabetes., Research Design and Methods: A total of 33 DR-related SNPs were identified by replicating published SNPs and via a genome-wide association study. Furthermore, we assessed the cumulative effects by creating a weighted genetic risk score and evaluated the discriminatory and prediction ability of these genetic variants using DN cases according to estimated glomerular filtration rate (eGFR) status along with a cohort with early renal functional decline (ERFD)., Results: Multivariate logistic regression models revealed that the DR-related SNPs afforded no individual or cumulative genetic effect on the nephropathy risk, eGFR status or ERFD outcome among patients with type two diabetes in Taiwan., Conclusion: Our findings indicate that larger studies would be necessary to clearly ascertain the effects of individual genetic variants and further investigation is also required to identify other genetic pathways underlying DN., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Adiponectin (APN) and its receptors have been reported to be associated with metabolic phenotypes. To better understand the effects of APN levels and its receptors on diabetic retinopathy (DR), we investigated the association of the plasma APN level and variations in APN-related genes with DR, individually and in combination.Patients with type 2 diabetes (T2D; N = 1604), above 20 years of age from the Taiwanese population participated in the study. Demographic information, blood pressure, and serological markers were recorded at enrollment. Genomic DNA was isolated and genotyped. The plasma APN levels were measured by enzyme-linked immunosorbent assay.T2D patients with DR (N = 632) had diabetes for a longer duration, and had higher HbA1c, and systolic and diastolic blood pressure compared to those without DR (N = 972) (P < .001, for all the parameters). Overall, 10 single nucleotide polymorphisms (SNPs) in ADIPOQ and CDH13 susceptibility loci were associated with DR. Gene risk score (GRS) was calculated based on 10 SNPs for each subject and the cumulative effect of genes was observed. Among the subjects with plasma APN level (N = 518), natural logarithm (LN) of APN (LN [APN]; odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.19-2.25) and GRS (OR = 1.90, 95% CI = 1.11-3.26 for middle range of GRS, and OR = 2.61, 95% CI = 1.48-4.59 for high range of GRS) were independent risk factors for DR after adjustment for other parameters.In conclusion, the plasma APN level and the genetic variations in adiponectin receptors were associated with DR.

The aim of this study is to explore the effect of genetic variation on diabetic retinopathy (DR) risk in a Taiwanese population. The logistic regression model was used to evaluate the relationship between DR status and risk factors, including the conventional parameters and genetic risk score (GRS). Candidate single nucleotide polymorphisms (SNPs) in GRS were selected based on previous reports with a combined P < 10 -4 (genome-wide association) and P < 0.05 (meta-analysis). In total, 58 SNPs in 44 susceptibility loci were selected, and four were used to calculate GRS. After adjustment for age, systolic blood pressure, diabetes duration, and HbA1c, the DR risk was 4.95 times higher for patients in the top GRS third tile than for those in the bottom third tile (95% CI = 2.99-8.18; P < 0.001). The addition of genetic information improved DR prediction, increasing the area under the curve (AUC) from 0.72 to 0.77 (P = 0.0024) and improving the sensitivity of the model such that 40 more subjects were reclassified into DR status. The developed multivariate logistic regression model combining conventional risk factors and the multilocus GRS can predict DR, thus enabling timely treatment to reduce blindness in T2D patients.

Human height can be described as a classical and inherited trait model. Genome-wide association studies (GWAS) have revealed susceptible loci and provided insights into the polygenic nature of human height. Familial short stature (FSS) represents a suitable trait for investigating short stature genetics because disease associations with short stature have been ruled out in this case. In addition, FSS is caused only by genetically inherited factors. In this study, we explored the correlations of FSS risk with the genetic loci associated with human height in previous GWAS, alone and cumulatively. We systematically evaluated 34 known human height single nucleotide polymorphisms (SNPs) in relation to FSS in the additive model (p < 0.00005). A cumulative effect was observed: the odds ratios gradually increased with increasing genetic risk score quartiles (p < 0.001; Cochran-Armitage trend test). Six affected genes-ZBTB38, ZNF638, LCORL, CABLES1, CDK10, and TSEN15-are located in the nucleus and have been implicated in embryonic, organismal, and tissue development. In conclusion, our study suggests that 13 human height GWAS-identified SNPs are associated with FSS risk both alone and cumulatively.

The purpose of this study is to characterize metallic elements associated with atmospheric particulate matter in the dry deposition plate, total suspended particulate, fine particles, and coarse particles at Taichung Harbor and Gong Ming Junior High School (airport) in central Taiwan at a sampling site from June 2013 to August 2013. The results indicated that: (1) the average concentrations of the metallic elements Cr and Cd were highest at the Gong Ming Junior High School (airport), and the average concentrations of the metallic elements Ni, Cu, and Pb were highest at the Taichung Harbor sampling site. (2) The high smelting industry density and export/import rate of heavily loaded cargos were the main reasons leading to these findings. (3) The average metallic element dry deposition and metallic element PM(2.5-10) all followed the order of Pb > Cr > Cu > Ni > Cd at the two sampling sites. However, the average metallic elements Cu and Pb were found to have the highest dry deposition velocities and concentrations in PM(2.5) for the two sampling sites in this study. (4) The correlation coefficients of ambient air particle dry deposition and concentration with wind speed at the airport were higher than those from the harbor sampling site. The wind and broad open spaces at Taichung Airport were the possible reasons for the increasing correlation coefficients for ambient air particle concentration and dry deposition with wind speed at the Taichung Airport sampling site.