1,569 research outputs found
The incidence of rheumatoid arthritis is predicted by rheumatoid factor titer in a longitudinal population study.
No full text
Investigation into laser re-melting of inconel 625 HVOF coating blended with WC
No full textHigh velocity oxy-fuel (HVOF) spraying of Diamalloy 1005 powders mixed with WC particles onto steel (304) is considered and laser re-melting of the resulting coatings is examined. Laser re-melting process is modeled to determine the melt layer thickness while temperature increase is formulated using the Fourier heating law. The morphological and metallurgical analyses prior and post laser re-melting process are carried out using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). X-ray diffraction (XRD) technique is used to determine the residual stress developed in the coating while the analytical formulation is adopted to predict the residual stress levels at the coating base material interface. The indentation tests are carried out to determine the Young’s modulus and fracture toughness of the coating prior to laser re-melting. Corrosion resistance of coating is measured using potentiodynamic polarization technique prior and post laser treatment process. The predictions of the melt layer thickness are in good agreement with experimental results. The presence of WC particles modifies temperature rise and its gradient in the coating while affecting the Young’s modulus, residual stress levels, and fracture toughness of the coating. The differences in the thermal properties of Inconel 625 powders and WC particles result in formation of small size cellular structure through polyphase solidification. WC dissolution in the central region of the large polycrystalline cells is observed due to the loss of carbon through carbonic gas formation. The results of corrosion tests prevail that significant improvement of corrosion resistance can be achieved after laser treatment process
Variants Associated with HDL-C Levels: Assessment for Association with Type 2 Diabetes in American Indians
No full textPrevious epidemiological studies in Pima Indians have identified a protective role for higher HDL-C against the onset of T2D in women. In this study, we analyzed 35 SNPs from established HDL-C loci for association with HDL-C, T2D and related traits. Genotyping and analysis of these SNPs in 2,717 full-heritage Pima Indians informative for T2D status and lipid levels identified a significant association (P<0.05) for 14 SNPs with HDL-C. An un-weighted multialleleic genetic risk score analysis (GRS) including the 35 SNPs was significantly associated with HDL-C (P=3.6×10-6), however the 21 SNPs not associated with HDL-C did not had any effect on HDL-C levels even in combination (GRS [21 SNPs], P=0.08). Therefore, only 14 SNPs were further genotyped in 4,993 American Indian samples informative for T2D (2,777 informative for lipid levels) and analyzed for association with HDL-C, T2D and related traits in the combined sample. In this analysis, 6 of the 14 SNPs at the CETP, DOCK6, PPP1R3B, ABCA1 and APOA1-C3-A4-A5 loci reached genome wide significance (P<4.9×10-7)for HDL-C association. The GRS analysis including the 14 loci in the combined samples negatively correlated with HDL-C levels (ß= -0.92mg/dL, P=3.1x10-48) and had a strong positive correlation with insulin resistance as estimated by homeostasis assessment (HOMA-IR, P=8.6x10-5, ß (SD units) = 0.015). The GRS correlated positively with T2D (P=0.007, OR=1.03), but there was no interaction with gender (P=0.74). When analyzed individually, SNPs at the CETP, HNF4A and KLF14 loci significantly associated with type 2 diabetes only in female subjects (3.2×10-4 - 7.7×10-5), such that the HDL-C lowering allele increased the risk for T2D. The T2D risk alleles for the SNPs at the CETP and KLF14 loci were associated with increased insulin resistance in female subjects as estimated by HOMA-IR (P<0.05). In conclusion, our studies suggest a modest effect of the genetic predisposition for lower HDL-C on the risk for T2D in American Indians
One-Hour Plasma Glucose Compared With 2-Hour Plasma Glucose in Relation to Diabetic Retinopathy in American Indians
No full textOBJECTIVE
We compared the ability of 1- and 2-h plasma glucose concentrations (1h-PG and 2h-PG, respectively), derived from a 75-g oral glucose tolerance test (OGTT), to predict retinopathy. 1h-PG and 2h-PG concentrations, measured in a longitudinal study of an American Indian community in the southwestern U.S., a population at high risk for type 2 diabetes, were analyzed to assess the usefulness of the 1h-PG to identify risk of diabetic retinopathy (DR).
RESEARCH DESIGN AND METHODS
Cross-sectional (n = 2,895) and longitudinal (n = 1,703) cohorts were assessed for the prevalence and incidence of DR, respectively, in relation to deciles of 1h-PG and 2h-PG concentrations. Areas under the receiver operating characteristic (ROC) curves for 1h-PG and 2h-PG were compared with regard to predicting DR, as assessed by direct ophthalmoscopy.
RESULTS
Prevalence and incidence of DR, based on direct ophthalmoscopy, changed in a similar manner across the distributions of 1h-PG and 2h-PG concentrations. ROC analysis showed that 1h-PG and 2h-PG were of similar value in identifying prevalent and incident DR using direct ophthalmoscopy. 1h-PG cut points of 230 and 173 mg/dL were comparable to 2h-PG cut points of 200 mg/dL (type 2 diabetes) and 140 mg/dL (impaired glucose tolerance), respectively.
CONCLUSIONS
1h-PG is a useful predictor of retinopathy risk, has a predictive value similar to that of 2h-PG, and may be considered as an alternative glucose time point during an OGTT
Differential methylation of genes in individuals exposed to maternal diabetes in utero
No full textAims/hypothesis
Individuals exposed to maternal diabetes in utero are more likely to develop metabolic and cardiovascular diseases later in life. This may be partially attributable to epigenetic regulation of gene expression. We performed an epigenome-wide association study to examine whether differential DNA methylation, a major source of epigenetic regulation, can be observed in offspring of mothers with type 2 diabetes during the pregnancy (OMD) compared with offspring of mothers with no diabetes during the pregnancy (OMND).
Methods
DNA methylation was measured in peripheral blood using the Illumina HumanMethylation450K BeadChip. A total of 423,311 CpG sites were analysed in 388 Pima Indian individuals, mean age at examination was 13.0 years, 187 of whom were OMD and 201 were OMND. Differences in methylation between OMD and OMND were assessed.
Results
Forty-eight differentially methylated CpG sites (with an empirical false discovery rate ≤0.05), mapping to 29 genes and ten intergenic regions, were identified. The gene with the strongest evidence was LHX3, in which six CpG sites were hypermethylated in OMD compared with OMND (p ≤ 1.1 × 10−5). Similarly, a CpG near PRDM16 was hypermethylated in OMD (1.1% higher, p = 5.6 × 10−7), where hypermethylation also predicted future diabetes risk (HR 2.12 per SD methylation increase, p = 9.7 × 10−5). Hypermethylation near AK3 and hypomethylation at PCDHGA4 and STC1 were associated with exposure to diabetes in utero (AK3: 2.5% higher, p = 7.8 × 10−6; PCDHGA4: 2.8% lower, p = 3.0 × 10−5; STC1: 2.9% lower, p = 1.6 × 10−5) and decreased insulin secretory function among offspring with normal glucose tolerance (AK3: 0.088 SD lower per SD of methylation increase, p = 0.02; PCDHGA4: 0.08 lower SD per SD of methylation decrease, p = 0.03; STC1: 0.072 SD lower per SD of methylation decrease, p = 0.05). Seventeen CpG sites were also associated with BMI (p ≤ 0.05). Pathway analysis of the genes with at least one differentially methylated CpG (p < 0.005) showed enrichment for three relevant biological pathways.
Conclusions/interpretation
Intrauterine exposure to diabetes can affect methylation at multiple genomic sites. Methylation status at some of these sites can impair insulin secretion, increase body weight and increase risk of type 2 diabetes
Autoantibodies Against PFDN2 Are Associated With An Increased Risk of Type 2 Diabetes: A Case-Control Study
No full textBackgroundThe adaptive immune system is involved in type 2 diabetes mellitus (T2DM), indicating the presence of unidentified autoantibodies that might be useful biomarkers for emerging immunomodulatory therapy. A prior microarray study with a small number of participants suggested the association of novel autoantibodies with T2DM in Southwest American Indians. We therefore sought to determine whether antibodies against 14 target proteins are associated with T2DM in a large case-control study.
MethodsParticipants were adults (age 20-59y) of Southwest American Indian heritage. Plasma antibodies against 14 possible target proteins were measured in 476 cases with T2DM of less than 5years duration and compared with 424 controls with normal glucose regulation.
ResultsHigher levels of antibodies against prefoldin subunit 2 (PFDN2) were associated with T2DM (P=.0001; Bonferroni-corrected threshold for multiple tests=0.0036 [=0.05]). The association between anti-PFDN2 antibodies and T2DM remained in multivariable logistic regression (odds ratio 1.27; 95% confidence interval, 1.09-1.49; per one SD difference in anti-PFDN2 antibody). The odds of T2DM were increased in the highest anti-PFDN2 antibody quintile by 66% compared with the lowest quintile. Differences in anti-PFDN2 antibodies were most prominent among cases with earlier onset of disease (ie, age 20-39y) compared with controls.
ConclusionsAnti-PFDN2 antibodies are associated with T2DM and might be a useful biomarker. These findings indicate that autoimmunity may play a role in T2DM in Southwest American Indians, especially among adults presenting with young onset of disease
One-hour and two-hour postload plasma glucose concentrations are comparable predictors of type 2 diabetes mellitus in Southwestern Native Americans
No full textAims/hypothesis Elevated 2-h plasma glucose concentration (2 h-PG) during a 75 g OGTT predict the development of type 2 diabetes mellitus. However, 1-h plasma glucose concentration (1 h-PG) is associated with insulin secretion and may be a better predictor of type 2 diabetes. We aimed to investigate the association between 1 h-PG and 2 h-PG using gold standard methods for measuring insulin secretion and action. We also compared 1 h-PG and 2 h-PG as predictors of type 2 diabetes mellitus.
Methods This analysis included adult volunteers without diabetes, predominantly Native Americans of Southwestern heritage, who were involved in a longitudinal epidemiological study from 1965 to 2007, with a baseline OGTT that included measurement of 1 h-PG. Group 1 (n = 716) underwent an IVGTT and hyperinsulinaemic-euglycaemic clamp for measurement of acute insulin response (AIR) and insulin-stimulated glucose disposal (M), respectively. Some members of Group 1 (n = 490 of 716) and members of a second, larger, group (Group 2; n = 1946) were followed-up to assess the development of type 2 diabetes (median 9.0 and 12.8 years follow-up, respectively).
Results Compared with 2 h-PG (r = -0.281), 1 h-PG (r = -0.384) was more closely associated with AIR, whereas, compared with 1 h-PG (r = -0.340), 2 h-PG (r = -0.408) was more closely associated with M. Measures of 1 h-PG and 2 h-PG had similar abilities to predict type 2 diabetes, which did not change when both were included in the model. A 1 h-PG cut-off of 9.3 mmol/l provided similar levels of sensitivity and specificity as a 2 h-PG cut-off of 7.8 mmol/l; the latter is used to define impaired glucose tolerance, a recognised predictor of type 2 diabetes mellitus.
Conclusions/interpretation The 1 h-PG was associated with important physiological predictors of type 2 diabetes and was as effective as 2 h-PG for predicting type 2 diabetes mellitus. The 1 h-PG is, therefore, an alternative method of identifying individuals with an elevated risk of type 2 diabetes mellitus
Use of Whole Genome Sequence Data to Design a Custom Genotyping Array for American Indians
No full textAmerican Indians have high rates of T2D and obesity, both being heritable characteristics with a strong genetic influence. Yet, genomic studies in this ethnic group have been hampered because currently available genotyping arrays are not well suited for capturing unique genetic architecture or ethnic specific variation. The goal of our study was to thoroughly interrogate the Pima Indian genome for T2D or obesity loci by obtaining whole genome sequence data and designing a custom genotyping array that tags all common variations. Sequence data from 335 Pima Indians identified 13M variants of which ~4.9 M had a minor allele frequency (maf) ≥5% among the sequenced samples and 66,558 variants had a MAF between 1-5% and were potentially functional (altered coding sequence or splice site). Of these 4,986,735 variants (87,850 novel), 4,777,625 (96%) could be captured by 703,797 tag markers (R2>0.85 for redundancy). These tag markers along with 227 mitochondrial markers and 1050 ancestry informative markers were incorporated on a custom genotyping array. To date, 3637 Pima Indians with longitudinal data on T2D and BMI, of which 550 subjects had additional data on related metabolic traits, have been genotyped with this array. Further genotyping in 4060 additional American Indians with longitudinal data on T2D and BMI is ongoing for the “top” 700 variants (variants with lowest p value for association with T2D or BMI in the 3637 subjects). Among those variants currently genotyped in all samples (N=7697), a novel damaging R1420H mutation in ABCC8 (carrier rate of 3.3%) was identified where H-allele carriers had higher birth weights (consistent with higher insulin levels during fetal growth) and an increased risk for T2D (OR=2.02 [1.47-2.78]), and a damaging R611C (rs34052647) in LIPE was identified that associated with T2D (OR= 1.36 [1.18-1.57]) and supported a prior study of LIPE as a diabetes loci in the Old Order Amish
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