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A 19-SNP coronary heart disease gene score profile in subjects with type 2 diabetes: the coronary heart disease risk in type 2 diabetes (CoRDia study) study baseline characteristics.

ABSTRACT: The coronary risk in diabetes (CoRDia) trial (n = 211) compares the effectiveness of usual diabetes care with a self-management intervention (SMI), with and without personalised risk information (including genetics), on clinical and behavioural outcomes. Here we present an assessment of randomisation, the cardiac risk genotyping assay, and the genetic characteristics of the recruits.Ten-year coronary heart disease (CHD) risk was calculated using the UKPDS score. Genetic CHD risk was determined by genotyping 19 single nucleotide polymorphisms (SNPs) using Randox's Cardiac Risk Prediction Array and calculating a gene score (GS). Accuracy of the array was assessed by genotyping a subset of pre-genotyped samples (n = 185).Overall, 10-year CHD risk ranged from 2-72 % but did not differ between the randomisation groups (p = 0.13). The array results were 99.8 % concordant with the pre-determined genotypes. The GS did not differ between the Caucasian participants in the CoRDia SMI plus risk group (n = 66) (p = 0.80) and a sample of UK healthy men (n = 1360). The GS was also associated with LDL-cholesterol (p = 0.05) and family history (p = 0.03) in a sample of UK healthy men (n = 1360).CHD risk is high in this group of T2D subjects. The risk array is an accurate genotyping assay, and is suitable for estimating an individual's genetic CHD risk. Trial registration This study has been registered at ClinicalTrials.gov; registration identifier NCT01891786.

SUBMITTER: Beaney KE

PROVIDER: S-EPMC5048451 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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A 19-SNP coronary heart disease gene score profile in subjects with type 2 diabetes: the coronary heart disease risk in type 2 diabetes (CoRDia study) study baseline characteristics.

Beaney Katherine E KE Ward Claire E CE Bappa Dauda A S DA McGale Nadine N Davies Anna K AK Hirani Shashivadan P SP Li KaWah K Howard Philip P Vance Dwaine R DR Crockard Martin A MA Lamont John V JV Newman Stanton S Humphries Steve E SE

Cardiovascular diabetology 20161003 1

<h4>Background</h4>The coronary risk in diabetes (CoRDia) trial (n = 211) compares the effectiveness of usual diabetes care with a self-management intervention (SMI), with and without personalised risk information (including genetics), on clinical and behavioural outcomes. Here we present an assessment of randomisation, the cardiac risk genotyping assay, and the genetic characteristics of the recruits.<h4>Methods</h4>Ten-year coronary heart disease (CHD) risk was calculated using the UKPDS score ...[more]

PMID: 27716211

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Project description:BackgroundMany patients with type 2 diabetes fail to achieve good glycaemic control. Poor control is associated with complications including coronary heart disease (CHD). Effective self-management and engagement in health behaviours can reduce risks of complications. However, patients often struggle to adopt and maintain these behaviours. Self-management interventions have been found to be effective in improving glycaemic control. Recent developments in the field of genetics mean that patients can be given personalised information about genetic- and lifestyle-associated risk of developing CHD. Such information may increase patients' motivation to engage in self-management. The Coronary Risk in Diabetes (CoRDia) trial will compare the effectiveness of a self-management intervention, with and without provision of personalised genetic- and lifestyle-associated risk information, with usual care, on clinical and behavioural outcomes, the cognitive predictors of behaviour, and psychological wellbeing.Methods/designParticipants will be adults aged 25-74 years registered with general practices in the East of England, diagnosed with type 2 diabetes, with no history of heart disease, and with a glycated haemoglobin level of ≥6.45% (47 mmol/mol). Consenting participants will be randomised to one of three arms: usual care control, group self-management only, group self-management plus personalised genetic- and lifestyle-associated risk information. The self-management groups will receive four weekly 2-hour group sessions, focusing on knowledge and information sharing, problem solving, goal setting and action planning to promote medication adherence, healthy eating, and physical activity. Primary outcomes are glycaemic control and CHD risk. Clinical data will be collected from GP records, including HbA1c, weight, body mass index, blood pressure, and HDL and total cholesterol. Self-reported health behaviours, including medication adherence, healthy eating and physical activity, and cognitive outcomes will be assessed by questionnaire. Measures will be taken at baseline, 3 months (questionnaire only), 6 months and 12 months post-baseline.DiscussionThis study will determine whether the addition of personalised genetic- and lifestyle-associated CHD risk information to a group self-management intervention improves diabetes control and CHD risk compared with group self-management and usual care. Effectiveness of the combined intervention on health behaviours cognitions theorised to predict them, and psychological outcomes will also be investigated.Trial registrationThis study has been registered at ClinicalTrials.gov; registration identifier NCT01891786 , registered 28 June 2013.

Project description:ObjectiveWe aimed to identify a lipidic profile associated with type 2 diabetes mellitus (T2DM) development in coronary heart disease (CHD) patients, to provide a new, highly sensitive model which could be used in clinical practice to identify patients at T2DM risk.MethodsThis study considered the 462 patients of the CORDIOPREV study (CHD patients) who were not diabetic at the beginning of the intervention. In total, 107 of them developed T2DM after a median follow-up of 60 months. They were diagnosed using the American Diabetes Association criteria. A novel lipidomic methodology employing liquid chromatography (LC) separation followed by HESI, and detection by mass spectrometry (MS) was used to annotate the lipids at the isomer level. The patients were then classified into a Training and a Validation Set (60-40). Next, a Random Survival Forest (RSF) was carried out to detect the lipidic isomers with the lowest prediction error, these lipids were then used to build a Lipidomic Risk (LR) score which was evaluated through a Cox. Finally, a production model combining the clinical variables of interest, and the lipidic species was carried out.ResultsLC-tandem MS annotated 440 lipid species. From those, the RSF identified 15 lipid species with the lowest prediction error. These lipids were combined in an LR score which showed association with the development of T2DM. The LR hazard ratio per unit standard deviation was 2.87 and 1.43, in the Training and Validation Set respectively. Likewise, patients with higher LR Score values had lower insulin sensitivity (P = 0.006) and higher liver insulin resistance (P = 0.005). The receiver operating characteristic (ROC) curve obtained by combining clinical variables and the selected lipidic isomers using a generalised lineal model had an area under the curve (AUC) of 81.3%.ConclusionOur study showed the potential of comprehensive lipidomic analysis in identifying patients at risk of developing T2DM. In addition, the lipid species combined with clinical variables provided a new, highly sensitive model which can be used in clinical practice to identify patients at T2DM risk. Moreover, these results also indicate that we need to look closely at isomers to understand the role of this specific compound in T2DM development. Trials registration NCT00924937.

Project description:Background: Observational studies have demonstrated that increased bone mineral density is associated with a higher risk of type 2 diabetes (T2D), but the relationship with risk of coronary heart disease (CHD) is less clear. Moreover, substantial uncertainty remains about the causal relevance of increased bone mineral density for T2D and CHD, which can be assessed by Mendelian randomisation studies. Methods: We identified 235 independent single nucleotide polymorphisms (SNPs) associated at p<5×10 -8 with estimated heel bone mineral density (eBMD) in 116,501 individuals from the UK Biobank study, accounting for 13.9% of eBMD variance. For each eBMD-associated SNP, we extracted effect estimates from the largest available GWAS studies for T2D (DIAGRAM: n=26,676 T2D cases and 132,532 controls) and CHD (CARDIoGRAMplusC4D: n=60,801 CHD cases and 123,504 controls). A two-sample design using several Mendelian randomization approaches was used to investigate the causal relevance of eBMD for risk of T2D and CHD. In addition, we explored the relationship of eBMD, instrumented by the 235 SNPs, on 12 cardiovascular and metabolic risk factors. Finally, we conducted Mendelian randomization analysis in the reverse direction to investigate reverse causality. Results: Each one standard deviation increase in genetically instrumented eBMD (equivalent to 0.14 g/cm 2) was associated with an 8% higher risk of T2D (odds ratio [OR] 1.08; 95% confidence interval [CI]: 1.02 to 1.14; p=0.012) and 5% higher risk of CHD (OR 1.05; 95%CI: 1.00 to 1.10; p=0.034). Consistent results were obtained in sensitivity analyses using several different Mendelian randomization approaches. Equivalent increases in eBMD were also associated with lower plasma levels of HDL-cholesterol and increased insulin resistance. Mendelian randomization in the reverse direction using 94 T2D SNPs or 52 CHD SNPs showed no evidence of reverse causality with eBMD. Conclusions: These findings suggest a causal relationship between elevated bone mineral density with risks of both T2D and CHD.

Dataset Information

A 19-SNP coronary heart disease gene score profile in subjects with type 2 diabetes: the coronary heart disease risk in type 2 diabetes (CoRDia study) study baseline characteristics.

Publications

A 19-SNP coronary heart disease gene score profile in subjects with type 2 diabetes: the coronary heart disease risk in type 2 diabetes (CoRDia study) study baseline characteristics.

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