5 results on '"Srivastava, PM"'
Search Results
2. Does left ventricular hypertrophy affect cognition and brain structural integrity in type 2 diabetes? Study design and rationale of the Diabetes and Dementia (D2) study.
- Author
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Patel SK, Restrepo C, Werden E, Churilov L, Ekinci EI, Srivastava PM, Ramchand J, Wai B, Chambers B, O'Callaghan CJ, Darby D, Hachinski V, Cumming T, Donnan G, Burrell LM, and Brodtmann A
- Subjects
- Aged, Aged, 80 and over, Australia epidemiology, Case-Control Studies, Cognitive Dysfunction epidemiology, Cognitive Dysfunction psychology, Dementia epidemiology, Dementia psychology, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 psychology, Female, Humans, Hypertrophy, Left Ventricular epidemiology, Hypertrophy, Left Ventricular psychology, Longitudinal Studies, Male, Middle Aged, Research Design, Surveys and Questionnaires, Brain diagnostic imaging, Cognitive Dysfunction diagnostic imaging, Dementia diagnostic imaging, Diabetes Mellitus, Type 2 diagnostic imaging, Hypertrophy, Left Ventricular diagnostic imaging
- Abstract
Background: Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer's disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline., Methods: The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months., Discussion: The D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk., Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12616000546459 ), date registered, 28/04/2016.
- Published
- 2017
- Full Text
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3. Genetic Variation in Kruppel like Factor 15 Is Associated with Left Ventricular Hypertrophy in Patients with Type 2 Diabetes: Discovery and Replication Cohorts.
- Author
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Patel SK, Wai B, Lang CC, Levin D, Palmer CNA, Parry HM, Velkoska E, Harrap SB, Srivastava PM, and Burrell LM
- Subjects
- Adult, Aged, Alleles, Diabetes Mellitus, Type 2 complications, Echocardiography, Female, Genotype, Humans, Hypertrophy, Left Ventricular complications, Hypertrophy, Left Ventricular genetics, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk Factors, Diabetes Mellitus, Type 2 pathology, Genetic Variation, Hypertrophy, Left Ventricular pathology, Kruppel-Like Transcription Factors genetics, Nuclear Proteins genetics
- Abstract
Left ventricular (LV) hypertrophy (LVH) is a heritable trait that is common in type 2 diabetes and is associated with the development of heart failure. The transcriptional factor Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy in experimental models. This study investigated if KLF15 gene variants were associated with LVH in type 2 diabetes. In stage 1 of a 2-stage approach, patients with type 2 diabetes and no known cardiac disease were prospectively recruited for a transthoracic echocardiographic assessment (Melbourne Diabetes Heart Cohort) (n=318) and genotyping of two KLF15 single nucleotide polymorphisms (SNPs) (rs9838915, rs6796325). In stage 2, the association of KLF15 SNPs with LVH was investigated in the Genetics of Diabetes Audit and Research in Tayside Scotland (Go-DARTS) type 2 diabetes cohort (n=5631). The KLF15 SNP rs9838915 A allele was associated in a dominant manner with LV mass before (P=0.003) and after (P=0.001) adjustment for age, gender, body mass index (BMI) and hypertension, and with adjusted septal (P<0.0001) and posterior (P=0.004) wall thickness. LVH was present in 35% of patients. Over a median follow up of 5.6years, there were 22 (7%) first heart failure hospitalizations. The adjusted risk of heart failure hospitalization was 5.5-fold greater in those with LVH and the rs9838915 A allele compared to those without LVH and the GG genotype (hazard ratio (HR) 5.5 (1.6-18.6), P=0.006). The association of rs9838915 A allele with LVH was replicated in the Go-DARTS cohort. We have identified the KLF15 SNP rs9838915 A allele as a marker of LVH in patients with type 2 diabetes, and replicated these findings in a large independent cohort. Studies are needed to characterize the functional importance of these results, and to determine if the SNP rs9838915 A allele is associated with LVH in other high risk patient cohorts., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
4. The CTGF gene -945 G/C polymorphism is not associated with cardiac or kidney complications in subjects with type 2 diabetes.
- Author
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Patel SK, Wai B, Macisaac RJ, Grant S, Velkoska E, Ord M, Panagiotopoulos S, Jerums G, Srivastava PM, and Burrell LM
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- Aged, Albuminuria genetics, Chi-Square Distribution, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 ethnology, Diabetic Nephropathies diagnosis, Diabetic Nephropathies ethnology, Diabetic Nephropathies physiopathology, Diastole genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Glomerular Filtration Rate genetics, Humans, Hypertrophy, Left Ventricular diagnostic imaging, Hypertrophy, Left Ventricular ethnology, Hypertrophy, Left Ventricular physiopathology, Kidney physiopathology, Linear Models, Male, Middle Aged, Multivariate Analysis, Phenotype, Promoter Regions, Genetic, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic ethnology, Renal Insufficiency, Chronic physiopathology, Risk Assessment, Risk Factors, Systole genetics, Ultrasonography, Ventricular Dysfunction, Left diagnostic imaging, Ventricular Dysfunction, Left ethnology, Ventricular Dysfunction, Left physiopathology, Ventricular Function, Left genetics, Victoria epidemiology, White People genetics, Connective Tissue Growth Factor genetics, Diabetes Mellitus, Type 2 genetics, Diabetic Nephropathies genetics, Hypertrophy, Left Ventricular genetics, Polymorphism, Genetic, Renal Insufficiency, Chronic genetics, Ventricular Dysfunction, Left genetics
- Abstract
Background: Connective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF -945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis. This study investigated the association of the CTGF -945 G/C promoter variant with cardiac complications (left ventricular (LV) hypertrophy (LVH), diastolic and systolic dysfunction) and chronic kidney disease (CKD) in type 2 diabetes., Methods: The CTGF -945 G/C polymorphism (rs6918698) was examined in 495 Caucasian subjects with type 2 diabetes. Cardiac structure and function were assessed by transthoracic echocardiography. Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albuminuria, and CKD defined as the presence of kidney damage (decreased kidney function (eGFR <60 ml/min/1.73 m2) or albuminuria)., Results: The mean age ± SD of the cohort was 62 ± 14 years, with a body mass index (BMI) of 31 ± 6 kg/m2 and median diabetes duration of 11 years [25th, 75th interquartile range; 5, 18]. An abnormal echocardiogram was present in 73% of subjects; of these, 8% had LVH alone, 74% had diastolic dysfunction and 18% had systolic ± diastolic dysfunction. CKD was present in 42% of subjects. There were no significant associations between the CTGF -945 G/C polymorphism and echocardiographic parameters of LV mass or cardiac function, or kidney function both before and after adjustment for covariates of age, gender, BMI, blood pressure and hypertension. CTGF -945 genotypes were not associated with the cardiac complications of LVH, diastolic or systolic dysfunction, nor with CKD., Conclusions: In Caucasians with type 2 diabetes, genetic variation in the CTGF -945 G/C polymorphism is not associated with cardiac or kidney complications.
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- 2012
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5. Association of ACE2 genetic variants with blood pressure, left ventricular mass, and cardiac function in Caucasians with type 2 diabetes.
- Author
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Patel SK, Wai B, Ord M, MacIsaac RJ, Grant S, Velkoska E, Panagiotopoulos S, Jerums G, Srivastava PM, and Burrell LM
- Subjects
- Adult, Aged, Angiotensin-Converting Enzyme 2, Blood Pressure genetics, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology, Female, Heart physiopathology, Humans, Hypertension diagnostic imaging, Hypertension epidemiology, Hypertension physiopathology, Hypertrophy, Left Ventricular diagnostic imaging, Hypertrophy, Left Ventricular physiopathology, Male, Middle Aged, Prevalence, Stroke Volume genetics, Ultrasonography, White People statistics & numerical data, Diabetes Mellitus, Type 2 physiopathology, Genetic Association Studies, Genetic Variation, Hypertension genetics, Hypertrophy, Left Ventricular genetics, Peptidyl-Dipeptidase A genetics, White People genetics
- Abstract
Background: Cardiovascular disease is common in diabetes, and is associated with activation of the renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE)2 is a recently described member of the RAS, and this study investigated whether ACE2 polymorphisms are associated with hypertension, left ventricular (LV) mass, and cardiac function in type 2 diabetes., Methods: Variants in ACE2 (rs1978124, rs2074192, rs4240157, rs4646156, rs4646188) were examined in 503 Caucasian subjects with type 2 diabetes. As ACE2 is located on the X chromosome, analyses were performed separately for men and women. Hypertension was defined by a history of hypertension, and/or antihypertensive medications or blood pressure (BP) >130/80 mm Hg. LV mass and systolic function (ejection fraction) were assessed by transthoracic echocardiography., Results: In men, hypertension was more prevalent with the ACE2 rs2074192 C allele (P = 0.023), rs4240157 G allele (P = 0.016) and rs4646188 T allele (P = 0.006). In men, the rs1978124 A allele was associated with a significantly lower ejection fraction compared to the G allele (62.3 ± 13.3 vs. 67.2 ± 10.9%, P = 0.002). This association remained significant after covariate adjustment for age, body mass index, hypertension, antihypertensive treatment, and BP. In women, the prevalence of hypertension was higher (P = 0.009) with the rs4240157 G allele, and the rs1978124 A allele was associated with significantly higher LV mass (P = 0.008)., Conclusions: In Caucasians with type 2 diabetes, genetic variation in ACE2 is associated with hypertension and reduced systolic function in men, and hypertension and increased LV mass in women.
- Published
- 2012
- Full Text
- View/download PDF
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