Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Study.
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SUBMITTER: Beeri MS
PROVIDER: S-EPMC6324406 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Depression has been identified as a risk factor for dementia among patients with type 2 diabetes mellitus but the cognitive domains and patient groups most affected have not been identified.To determine whether comorbid depression in patients with type 2 diabetes accelerates cognitive decline.A 40-month cohort study of participants in the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) trial.Fifty-two clinics organized into 6 clinical networks across the United States and Canada.Two thousand nine hundred seventy-seven participants with type 2 diabetes at high risk for cardiovascular events.The Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and the modified Stroop test were used to assess cognition. The 9-item Patient Health Questionnaire was used to assess depression.Mixed-effects statistical models were used to analyze cognitive test outcomes incorporating depression as a time-dependent covariate.Participants with scores indicative of depression (9-item Patient Health Questionnaire, ?10) showed greater cognitive decline during 40-month follow-up on all tests, with the following differences in estimated least squares means: Digit Symbol Substitution Test, 0.72 (95% CI, 0.25 to 1.19; P = .003), Rey Auditory Verbal Learning Test, 0.18 (95% CI, 0.07 to 0.29; P = .001), and Stroop interference, -1.06 (95% CI, -1.93 to -0.18; P = .02). This effect of depression on risk of cognitive decline did not differ according to previous cardiovascular disease; baseline cognition or age; or intensive vs standard glucose-lowering treatment, blood pressure treatment, lipid treatment, or insulin treatment. Addition of demographic and clinical covariates to models did not significantly change the cognitive decline associated with depression.Depression in patients with type 2 diabetes was associated with greater cognitive decline in all domains, across all treatment arms, and in all participant subgroups assessed. Future randomized trials will be necessary to determine if depression treatment can lower the risk of cognitive decline in patients with diabetes.
| S-EPMC4212406 | biostudies-literature
Project description:IntroductionHigh blood glucose levels may be responsible for the increased risk for dementia in diabetic patients.MethodsA secondary data analysis merging electronic medical records (EMRs) with data collected from the Indianapolis-Ibadan Dementia project (IIDP). Of the enrolled 4105 African Americans, 3778 were identified in the EMR. Study endpoints were dementia, mild cognitive impairment (MCI), or normal cognition. Repeated serum glucose measurements were used as the outcome variables.ResultsDiabetic participants who developed incident dementia had a significant decrease in serum glucose levels in the years preceding the diagnosis compared to the participants with normal cognition (P = .0002). They also had significantly higher glucose levels up to 9 years before the dementia diagnosis (P = .0367).DiscussionHigh glucose levels followed by a decline occurring years before diagnosis in African American participants with diabetes may represent a powerful presymptomatic metabolic indicator of dementia.
| S-EPMC5318260 | biostudies-literature
Project description:BackgroundAlbuminuria is associated with cognitive impairment in people with type 2 diabetes mellitus (T2DM). The brain volume correlates of albuminuria in people with T2DM have not been well investigated.MethodsWe examined 502 individuals with T2DM (9-12 years duration; mean age ~62 years) who had a brain MRI at baseline and at 40 months. Baseline MRI findings were examined by the presence or absence of albuminuria (≥30mg/g creatinine). Changes in MRI findings were examined by whether albuminuria was persistent, intermittent, or absent during follow-up.ResultsAt baseline, participants with albuminuria (28.7% of the cohort) had more abnormal white matter volume (AWMV) than participants without albuminuria on unadjusted analysis. This difference was attenuated with adjustment for systolic blood pressure, which was higher in participants with albuminuria than in those without albuminuria. During ~3.5 years of follow-up, participants with persistent albuminuria (15.8%) had a greater increase in new AWMV than participants without albuminuria (59.8%) or those with intermittent albuminuria on unadjusted analysis. This difference was attenuated with adjustment for age and systolic blood pressure. There were no significant differences in gray matter volume and total brain volume between participants with or without albuminuria at baseline or during follow-up. There was no significant effect modification of these findings by estimated glomerular filtration rate (eGFR) at baseline or change in eGFR during follow-up.ConclusionsIn this diabetic cohort, baseline albuminuria and persistent albuminuria were not independently associated with any significant differences in brain volume measurements compared with participants without albuminuria.
| S-EPMC4888390 | biostudies-literature
Project description:Background and purposeRates of type 2 diabetes are higher among African Americans compared with individuals of European ancestry. The purpose of this investigation was to determine the relationship between MR imaging measures of brain structure (volume of GM, WM, WM lesions) and cognitive function in a population of African Americans with type 2 diabetes. These MR imaging measures of brain structure are affected by type 2 diabetes-associated macrovascular and microvascular disease and may be associated with performance on tasks of cognitive function in the understudied African American population.Materials and methodsAfrican Americans with type 2 diabetes enrolled in the African American-Diabetes Heart Study MIND study (n = 263) were evaluated across a broad range of cognitive domains and imaged with brain MR imaging. Associations between cognitive parameters and MR imaging measures of whole-brain GM, WM, and WM lesion volumes were assessed by using adjusted multivariate models.ResultsLower GM volume was associated with poorer performance on measures of general cognitive function, working memory, and executive function. Higher WM lesion volume was associated with poorer performance on a smaller subset of cognitive domains compared with GM volume but included aspects of working memory and executive function. There were no statistically significant associations with WM volume.ConclusionsMarkers of cortical atrophy and WM lesion volume are associated with cognitive function in African Americans with type 2 diabetes. These associations are described in an African American cohort with disease control similar to that of individuals of European ancestry, rather than underserved African Americans with poor access to health care. Interventions to reduce cortical atrophy and WM disease may improve cognitive outcomes in this understudied population.
| S-EPMC4857016 | biostudies-literature
Project description:Aims/hypothesisThe Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, a double 2x2 factorial parallel-group randomised clinical trial, tested whether intensive compared with standard management of hyperglycaemia, BP or lipid levels reduced cognitive decline and brain atrophy in 2977 people with type 2 diabetes. We describe the results of the observational extension study, ACCORDION MIND (ClinicalTrials.gov registration no. NCT00182910), which aimed to measure the long-term effects of the three ACCORD interventions on cognitive and brain structure outcomes approximately 4 years after the trial ended.MethodsParticipants (mean diabetes duration 10 years; mean age 62 years at baseline) received a fourth cognitive assessment and a third brain MRI, targeted at 80 months post-randomisation. Primary outcomes were performance on the Digit Symbol Substitution Test (DSST) and total brain volume (TBV). The contrast of primary interest compared glycaemic intervention groups at the ACCORDION visit; secondary contrasts were the BP and lipid interventions.ResultsOf the surviving ACCORD participants eligible for ACCORDION MIND, 1328 (68%) were re-examined at the ACCORDION follow-up visit, approximately 47 months after the intensive glycaemia intervention was stopped. The significant differences in therapeutic targets for each of the three interventions (glycaemic, BP and lipid) were not sustained. We found no significant difference in 80 month mean change from baseline in DSST scores or in TBV between the glycaemic intervention groups, or the BP and lipid interventions. Sensitivity analyses of the sites with ≥70% participation at 80 months revealed consistent results.Conclusions/interpretationThe ACCORD interventions did not result in long-term beneficial or adverse effects on cognitive or brain MRI outcomes at approximately 80 months follow-up. Loss of separation in therapeutic targets between treatment arms and loss to follow-up may have contributed to the lack of detectable long-term effects.Trial registrationClinicalTrials.gov NCT00182910.
| S-EPMC5633725 | biostudies-literature
Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD - Imaging)
| PRJNA1079425 | ENA
Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD - Imaging)
| PRJNA1079426 | ENA
Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD-BioLINCC)
| PRJNA1075472 | ENA
Project description:Diabetic nephropathy is the leading cause of end-stage renal disease. The urinary albumin to creatinine ratio is used as a predictor for the development of nephropathy but it is neither sensitive nor specific. Here we used liquid chromatography/mass spectrometry on urine of eight normoalbuminuric patients with type 2 diabetes from the VA Diabetes Trial to identify candidate markers for loss of renal function. Initial verification of seven markers (agrin, haptoglobin, mannan-binding lectin serine protease 2, LAMP-2, angiotensinogen, NGAL, and uromodulin) in the urine of an additional 30 patients showed that haptoglobin was the best predictor of early renal functional decline. We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio <300 mg/g). In comparing the highest to lowest tertiles, the odds ratio for having early renal function decline was 2.70 (CI: 1.15, 6.32) using the haptoglobin to creatinine ratio compared with 2.50 (CI 1.14, 5.48) using the albumin to creatinine ratio after adjusting for treatment group and use of ACE inhibitors. Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance. Thus, the haptoglobin to creatinine ratio may be useful to predict patients with type 2 diabetes at risk of nephropathy before the development of macroalbuminuria or reduced glomerular filtration rate.
| S-EPMC3672380 | biostudies-literature
Project description:African Americans (AAs) are disproportionately affected by metabolic diseases and adverse drug events, with limited publicly available genomic and transcriptomic data to advance the knowledge of the molecular underpinnings or genetic associations to these diseases or drug response phenotypes. To fill this gap, we obtained 60 primary hepatocyte cultures from AA liver donors for genome-wide mapping of expression quantitative trait loci (eQTL) using LAMatrix. We identified 277 eGenes and 19,770 eQTLs, of which 67 eGenes and 7,415 eQTLs are not observed in the Genotype-Tissue Expression Project (GTEx) liver eQTL analysis. Of the eGenes found in GTEx only 25 share the same lead eQTL. These AA-specific eQTLs are less correlated to GTEx eQTL in effect sizes and have larger Fst values compared to eQTLs found in both cohorts (overlapping eQTLs). We assessed the overlap between GWAS variants and their tagging variants with AA hepatocyte eQTLs and demonstrated that AA hepatocyte eQTLs can decrease the number of potential causal variants at GWAS loci. Additionally, we identified 75,002 exon QTLs of which 48.8% are not eQTLs in AA hepatocytes. Our analysis provides the first comprehensive characterization of AA hepatocyte eQTLs and highlights the unique discoveries that are made possible due to the increased genetic diversity within the African ancestry genome.
2020-03-27 | GSE147628 | GEO