134 research outputs found

    Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

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    South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ2 = 7.72, P = 0.02). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P = 0.0001), HDL cholesterol (P = 0.009), LDL cholesterol (P = 0.02), and diabetes status (P < 0.05). Arylesterase activity was only associated with HDL cholesterol (P = 0.003). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients

    Cardiovascular disease risk profile and microvascular complications of diabetes: comparison of Indigenous cohorts with diabetes in Australia and Canada

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    <p>Abstract</p> <p>Background</p> <p>Indigenous populations of Australia and Canada experience disproportionately high rates of chronic disease. Our goal was to compare cardiovascular (CVD) risk profile and diabetes complications from three recent comprehensive studies of diabetes complications in different Indigenous populations in Australia and Canada.</p> <p>Methods</p> <p>We compared participants from three recent studies: remote Indigenous Australians (2002-2003, n = 37 known diabetes), urban Indigenous Australians (2003-2005, n = 99 known diabetes), and remote Aboriginal Canadians (2001-2002, n = 188 known diabetes).</p> <p>Results</p> <p>The three groups were similar for HbA1c, systolic BP, diabetes duration. Although leaner by body-mass-index criteria, remote Indigenous Australians displayed a more adverse CVD risk profile with respect to: waist-hip-ratio (1.03, 0.99, 0.94, remote Indigenous Australians, urban Indigenous Australians, remote Canadians, p < 0.001); HDL-cholesterol (0.82, 0.96, 1.17 mmol/L, p < 0.001); urine albumin-creatinine-ratio (10.3, 2.4, 4.5 mg/mmol); and C-reactive protein. With respect to diabetes complications, microalbuminuria (50%, 25%, 41%, p = 0.001) was more common among both remote groups than urban Indigenous Australians, but there were no differences for peripheral neuropathy, retinopathy or peripheral vascular disease.</p> <p>Conclusions</p> <p>Although there are many similarities in diabetes phenotype in Indigenous populations, this comparison demonstrates that CVD risk profiles and diabetes complications may differ among groups. Irrespective, management and intervention strategies are required from a young age in Indigenous populations and need to be designed in consultation with communities and tailored to community and individual needs.</p

    Assessing the association of the HNF1A G319S variant with C-reactive protein in Aboriginal Canadians: a population-based epidemiological study

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    <p>Abstract</p> <p>Background</p> <p>C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased risk of developing cardiovascular disease. Common variants of the hepatocyte nuclear factor 1A (<it>HNF1A) </it>gene encoding HNF-1α have been associated with plasma CRP in predominantly European Caucasian samples. <it>HNF1A </it>might therefore have an impact on vascular disease and diabetes risk that is mediated by CRP. In an Aboriginal Canadian population, a private polymorphism, <it>HNF1A </it>G319S, was associated with increased prevalence of type 2 diabetes. However, it has not been investigated whether this association is mediated by CRP. We aimed to investigate whether CRP was mediating the association between <it>HNF1A </it>G319S and type 2 diabetes in an Aboriginal Canadian population with a high prevalence of diabetes.</p> <p>Methods</p> <p>A total of 718 individuals who participated in a diabetes prevalence and risk factor survey were included in the current analysis. Participants were genotyped for <it>HNF1A </it>G319S. Fasting plasma samples were analyzed for CRP. Fasting plasma glucose and a 75-g oral glucose tolerance test were obtained to determine type 2 diabetes.</p> <p>Results</p> <p>The prevalence rate of type 2 diabetes was 17.4% (125/718) using the 1999 World Health Organization definition and was higher among S319 allele carriers compared to G/G homozygotes (p < 0.0001). Among participants without type 2 diabetes, CRP levels were higher among G/G homozygotes (1.64 [95% confidence interval 1.35-2.00] mg/l) than in S319 carriers (1.26 [1.04-1.54] mg/l) (p = 0.009) after adjustment for age, sex, 2-h post-load glucose, waist circumference, and serum amyloid A. CRP levels were elevated among those with diabetes after similar adjustment (4.39 [95% confidence interval 3.09-6.23] and 4.44 [3.13-6.30] mg/L, respectively), and no significant difference in CRP was observed between S319 carriers and non-carriers (p = 0.95).</p> <p>Conclusions</p> <p>CRP levels were lower in S319 allele carriers of the <it>HNF1A </it>gene compared to non-carriers among individuals without diabetes, but this difference was not present among those with diabetes, who uniformly had elevated CRP levels. Therefore, while <it>HNF1A </it>appears to influence CRP concentrations in the non-diabetic state, chronic elevation of CRP is unlikely mediating the association between the <it>HNF1A </it>polymorphism and the high prevalence of type 2 diabetes in this Aboriginal population.</p

    Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample

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    <p>Abstract</p> <p>Background</p> <p>Common polymorphisms in the promoter of the <it>APOC3 </it>gene have been associated with hypertriglyceridemia and may impact on phenotypic expression of the metabolic syndrome (MetS). The rs7566605 marker, located near the <it>INSIG2 </it>gene, has been found to be associated with obesity, making it also a potential genetic determinant for MetS. The objective of this study is to examine the <it>APOC3 </it>-455T>C and the <it>INSIG2 </it>rs7566605 polymorphisms as potential genetic determinants for MetS in a multi-ethnic sample.</p> <p>Methods</p> <p>Subjects were genotyped for both the <it>APOC3 </it>-455T>C and <it>INSIG2 </it>rs7566605 polymorphisms, and classified for the presence or absence of MetS (NCEP ATP III and IDF definitions). The total study population included 2675 subjects (≥18 years of age) from six different geographical ancestries.</p> <p>Results</p> <p>For the overall study population, the prevalence of MetS was 22.6% (NCEP ATP III definition). Carriers of ≥1 copy of <it>APOC3 </it>-455C were more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of the association was related not only to a higher proportion of -455C carriers meeting the triglyceride and high-density lipoprotein cholesterol criteria, but also the blood pressure criteria compared with wild-type homozygotes. Plasma apo C-III concentrations were not associated with <it>APOC3 </it>-455T>C genotype. The <it>INSIG2 </it>rs7566605 polymorphism was not associated with MetS or measures of obesity.</p> <p>Conclusion</p> <p>Meta-analysis of the sample of multiple geographic ancestries indicated that the functional -455T>C promoter polymorphism in <it>APOC3 </it>was associated with an approximately 2-fold increased risk of MetS, whereas the <it>INSIG2 </it>rs7566605 polymorphism was not associated with MetS.</p

    HNF1A G319S variant, active cigarette smoking and incident type 2 diabetes in Aboriginal Canadians: a population-based epidemiological study

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    <p>Abstract</p> <p>Background</p> <p>In a recent report of large-scale association analysis, a type 2 diabetes susceptibility locus near <it>HNF1A </it>was identified in predominantly European descent populations. A population-specific G319S polymorphism in <it>HNF1A </it>was previously identified in Aboriginal Canadians who have a high prevalence of type 2 diabetes. We aimed to investigate the association of the <it>HNF1A </it>G319S polymorphism with incident type 2 diabetes and to assess whether clinical risk variables for type 2 diabetes influence the association in an Aboriginal population.</p> <p>Methods</p> <p>Of 606 participants who were free of diabetes at baseline in 1993-1995, 540 (89.1%) participated in 10-year follow-up assessments in 2003-2005. Fasting glucose and a 75-g oral glucose tolerance test were obtained to determine incident type 2 diabetes. Participants were genotyped for the <it>HNF1A </it>G319S polymorphism. Interviewers administered questionnaires on smoking behavior.</p> <p>Results</p> <p>The incidence rates of type 2 diabetes were 14.2% (55/388) in major allele homozygotes and 31.2% (29/93) in minor allele carriers (p < 0.001). The <it>HNF1A </it>G319S carrier status was associated with incident type 2 diabetes (odds ratio [OR] 3.78 [95% CI 2.13-6.69]) after adjustment for age, sex, hypertension, triglyceride, HDL cholesterol, and waist circumference. A statistical interaction was observed between <it>HNF1A </it>G319S and baseline active cigarette smoking on the development of type 2 diabetes with similar adjustment (p = 0.006). When participants were stratified by baseline smoking status, <it>HNF1A </it>G319S carriers who were active smokers had increased risk of developing diabetes (OR 6.91 [95% CI 3.38-14.12]), while the association was attenuated to non-significance among non-smokers (1.11 [0.40-3.08]).</p> <p>Conclusions</p> <p>The <it>HNF1A </it>G319S variant is associated with incident type 2 diabetes in Aboriginal Canadians. Furthermore, cigarette smoking appears to amplify incident diabetes risk in carriers of <it>HNF1A </it>G319S.</p

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

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    Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care
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