Diabetes In African Americans Research Articles

Admixture mapping of serum vitamin D and parathyroid hormone concentrations in the African American—Diabetes Heart Study

Vitamin D and intact parathyroid hormone (iPTH) concentrations differ between individuals of African and European descent and may play a role in observed racial differences in bone mineral density (BMD). These findings suggest that mapping by admixture linkage disequilibrium (MALD) may be informative for identifying genetic variants contributing to these ethnic disparities. Admixture mapping was performed for serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, vitamin D-binding protein (VDBP), bioavailable vitamin D, and iPTH concentrations and computed tomography measured thoracic and lumbar vertebral volumetric BMD in 552 unrelated African Americans with type 2 diabetes from the African American—Diabetes Heart Study. Genotyping was performed using a custom Illumina ancestry informative marker (AIM) panel. For each AIM, the probability of inheriting 0, 1, or 2 copies of a European-derived allele was determined. Non-parametric linkage analysis was performed by testing for association between each AIM using these probabilities among phenotypes, accounting for global ancestry, age, and gender. Fine-mapping of MALD peaks was facilitated by genome-wide association study (GWAS) data. VDBP levels were significantly linked in proximity to the protein coding locus (rs7689609, LOD=11.05). Two loci exhibited significant linkage signals for 1,25-dihydroxyvitamin D on 13q21.2 (rs1622710, LOD=3.20) and 12q13.2 (rs11171526, LOD=3.10). iPTH was significantly linked on 9q31.3 (rs7854368, LOD=3.14). Fine-mapping with GWAS data revealed significant known (rs7041 with VDBP, P=1.38×10−82) and novel (rs12741813 and rs10863774 with VDBP, P<6.43×10−5) loci with plausible biological roles. Admixture mapping in combination with fine-mapping has focused efforts to identify loci contributing to ethnic differences in vitamin D-related traits.

Aldosterone, Renin, and Diabetes Mellitus in African Americans: The Jackson Heart Study.

Previous research has suggested that activation of the renin-angiotensin-aldosterone system may promote insulin resistance and β-cell dysfunction, but the association with incident diabetes in African Americans is unknown. We examined the association of aldosterone and renin with insulin resistance, β-cell function, and incident diabetes in a large African American cohort. The Jackson Heart Study is a prospective study of the development and progression of cardiovascular disease in African Americans. Participants were recruited from the tricounty area of metropolitan Jackson, Mississippi. A total of 5301 African American adults, aged 21–94 years, were assessed at baseline and through 12 years of follow-up. Data on aldosterone, renin, and risk factors were collected at baseline (2000–2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at baseline and through 12 years of follow-up. Participants were excluded for missing data on baseline covariates or diabetes follow-up. Cox regression was used to estimate hazard ratios (HR) for incident diabetes using sequential modeling adjusting for age, sex, education, occupation, systolic blood pressure, current smoking, physical activity, dietary intake, and body mass index. Aldosterone, renin, and diabetes risk factors were measured. Outcomes included the homeostatic model assessment of insulin resistance (HOMA-IR) and incident diabetes. Among 3234 participants over a median of 8.0 years of follow-up, there were 554 cases of incident diabetes. Every 1% increase in log-transformed aldosterone was associated with a 0.18% higher log-transformed HOMA-IR in cross-sectional analyses of nondiabetic participants (P < .001). Log-transformed aldosterone and renin levels in the fifth vs first quintile were associated with a 78% (HR 1.78, 95% confidence interval 1.35–2.34) and 35% (HR 1.35, 95% confidence interval 1.06–1.72) increase in diabetes risk, respectively, in fully adjusted models. Activation of the renin-angiotensin-aldosterone system may play a significant role in the development of insulin resistance and diabetes in African Americans.

Plasma FGF23 and Calcified Atherosclerotic Plaque in African Americans with Type 2 Diabetes Mellitus

Background: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial. Methods: Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate. Results: The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m², urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up. Conclusions: Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.

Association of ADIPOQ gene with type 2 diabetes and related phenotypes in African American men and women: the Jackson Heart Study.

BackgroundAfrican Americans experience disproportionately higher prevalence of type 2 diabetes and related risk factors. Little research has been done on the association of ADIPOQ gene on type 2 diabetes, plasma adiponectin, blood glucose, HOMA-IR and body mass index (BMI) in African Americans. The objective of our research was to assess such associations with selected SNPs. The study included a sample of 3,020 men and women from the Jackson Heart Study who had ADIPOQ genotyping information. Unadjusted and adjusted regression models with covariates were used with type 2 diabetes and related phenotypes as the outcome stratified by sex.ResultsThere was no association between selected ADIPOQ SNPs with type 2 diabetes, blood glucose, or BMI in men or women. There was a significant association between variant rs16861205 and lower adiponectin in women with minor allele A in the fully adjusted model (β(SE) p = −.13(0.05), 0.003). There was also a significant association with variant rs7627128 and lower HOMA-IR among men with minor allele A in the fully adjusted model (β(SE) p = −0.74(0.20), 0.0002).ConclusionsThese findings represent new insights regarding the association of ADIPOQ gene and type 2 diabetes and related phenotypes in African American men and women.

Novel Risk Factors for Type 2 Diabetes in African-Americans.

In the USA, compared to whites, African-Americans are disproportionately impacted by the diabetes epidemic. Traditional diabetes risk factors, such as obesity, are more common among African-Americans, but these traditional risk factors do not explain all of the disparity in diabetes risk. Recent research has identified novel environmental, lifestyle, physiologic, and genetic risk factors for diabetes, some of which appear to impact African-Americans more than whites. This manuscript reviews the recent literature to highlight some of these novel risk factors that may be contributing to the racial disparity in diabetes risk. Further study is needed of the modifiable risk factors for development of interventions to reduce the risk of diabetes in African-Americans, as well as other high-risk populations.

Genetics of Type 2 Diabetes in African Americans.

Type 2 diabetes (T2D) is a global health problem showing substantial ethnic disparity in disease prevalence. African Americans have one of the highest prevalence of T2D in the USA but little is known about their genetic risks. This review summarizes the findings of genetic regions and loci associated with T2D and related glycemic traits using linkage, admixture, and association approaches in populations of African ancestry. In particular, findings from genome-wide association and exome chip studies suggest the presence of both ancestry-specific and shared loci for T2D and glycemic traits. Among the European-identified loci that are transferable to individuals of African ancestry, allelic heterogeneity as well as differential linkage disequilibrium and risk allele frequencies pose challenges and opportunities for fine mapping and identification of causal variant(s) by trans-ancestry meta-analysis. More genetic research is needed in African ancestry populations including the next-generation sequencing to improve the understanding of genetic architecture of T2D.

Effects of Type 2 Diabetes on Brain Structure and Cognitive Function: African American-Diabetes Heart Study MIND.

Rates 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. African 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. Lower 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. Markers 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.

Associations Between Diabetes and Cognitive Function in Socioeconomically Diverse African American and White Men and Women.

To examine whether race and poverty (income <125% of the federal poverty limit), modifies associations between diabetes and cognition in a biracial, urban-dwelling sample. Cross-sectional data for 2066 participants (mean age = 47.6 years, 56.8% women, 56.2% African American, 38.6% below poverty) from the first wave of the Healthy Aging in Neighborhoods of Diversity across the Life Span study were used for analyses. Eleven tests measured cognitive function. Interactions among diabetes, race, and poverty status with cognition were assessed in multiple regression analyses. Significant interactions among diabetes, race, and poverty status were observed. Among African Americans below poverty, diabetic individuals performed lower than nondiabetic individuals on California Verbal Learning Test Free Recall Short Delay (z = -0.444 [0.123] versus z = -0.137 [0.045]) and Long Delay (z = -0.299 [0.123] versus z = -0.130 [0.045]), Digit Span Backward (z = -0.347 [0.109] versus z = -0.072 [0.041]), and the Brief Test of Attention (z = -0.452 [-0.099] versus z = -0.099 [0.047]), and higher on Category Fluency (z = 0.114 [0.117] versus z = -0.118 [0.044]). No consistent differences between diabetic and nondiabetic individuals were found for African American and white participants above poverty. Diabetes was associated with poorer verbal memory, working memory, and attention among African Americans living in poverty. Diabetic African Americans below poverty may have increased risk of cognitive deficit at a younger age. Improving health literacy, doctor-patient communication, and multidisciplinary medical care for impoverished individuals may reduce differences. Additional research is needed to clarify mechanisms underlying these associations.

Can L-Cysteine and Vitamin D Rescue Vitamin D and Vitamin D Binding Protein Levels in Blood Plasma of African American Type 2 Diabetic Patients?

Aims: Vitamin D (VD) deficiency has become a worldwide epidemic, particularly affecting African Americans (AA). VD deficiency has been implicated in the excessive rate of complications associated with diabetes in AA. Blood levels of VD binding protein (VDBP) and glutathione (GSH) are lower in AA compared with those in Caucasians. This study tested the hypothesis that lower GSH levels are linked to VDBP and VD deficiency in AA-type 2 diabetic (AA-T2D) patients. Blood was analyzed from T2D and nondiabetic subjects (N). Experiments examining GSH deficiency and l-cysteine (LC) supplementation were performed using THP-1 monocytes. Results: Plasma levels of LC, GSH, VDBP, and VD were significantly lower in AA-T2D compared with age-matched AA-N or Caucasian-T2D. Lower levels of LC and GSH showed a significant positive correlation with lower VDBP and VD levels in AA-T2D. GSH deficiency investigated using an antisense approach depleted VDBP/vitamin D receptor (VDR); LC supplementation caused significant upregulation of GSH and of VDBP/VDR, while supplementation with VD+LC caused a significantly greater GSH and VDBP/VDR upregulation compared with that of VD alone in monocytes. Innovation and Conclusion: The reported observations suggest that VD deficiency may be linked to GSH and LC status and lead to a novel hypothesis that supplementation with LC in combination with VD will be effective in increasing VD levels and reducing health disparities in AA. Antioxid. Redox Signal. 23, 688–693.

Abstract P157: Serum Vitamin D is Not Associated With Risk of Incident Diabetes in African Americans: The Jackson Heart Study

A recent meta-analysis of cohort studies with participants primarily of European ancestry, concluded that the risk of incident diabetes was inversely proportional to serum 25-hydroxy-vitamin D levels (25-OH-D). African Americans have lower levels of vitamin D than European Americans. But, lower levels of vitamin D do not seem to carry the same risk for low bone density or vascular calcification for African Americans. We sought to test the hypothesis that low vitamin D elevates the risk of diabetes in African Americans. During 2001-5, 5301 African American adults in Jackson, MS, were examined and blood samples drawn; mean age was 55±13. Serum 25-OH-D2 and 25-OH-D3 were measured from stored frozen serum; mean total 25-OH-D (25-OH-D2 plus 25-OH-D3) =14.5±6.7ng/ml. A seasonal pattern was evident for 25-OH-D3 but not for 25-OH-D2 levels. A cosinor model adjusted for seasonality of 25-OH-D3; mean annualized concentrations and seasonal amplitude were significantly higher for men and for persons of normal BMI compared to overweight or obese persons. Total 25-OH-D, as the sum of predicted annualized mean 25-OH-D3 and measured 25-OH-D2, was used in subsequent analysis. The analysis evaluated 3363 participants after exclusions for missing serum vitamin D (n=141), prevalent diabetes (n=1152), incomplete ascertainment of diabetes (n=62), or no follow-up (n=725). During a mean follow-up of 7.1 years, there were 584 new cases of diabetes. Using a Cox Proportional Hazards model controlling for age and sex, the risk of incident diabetes was significantly and inversely associated with total serum 25-OH-D; after adding BMI to the model, 25-OH-D was not significantly associated with risk of diabetes (Table 1). Physical activity, smoking, and alcohol use did not predict incident diabetes in any model. In conclusion, we found that in this cohort of African-Americans, with low mean 25-OH-D and a relatively narrow range of 25-OH-D, the risk of incident diabetes was not associated with serum 25-OH-D levels after controlling for sex, age, and BMI.

Markers of endothelial dysfunction and inflammation predict progression of diabetic nephropathy in African Americans with type 1 diabetes

African Americans with early onset type 1 diabetes mellitus are at a high risk for severe diabetic nephropathy and end-stage renal disease. In order to determine whether baseline plasma levels of inflammatory markers predict incidence of overt proteinuria or renal failure in African Americans with type 1 diabetes mellitus we reexamined data of 356 participants in our observational follow-up study of 725 New Jersey African-Americans with Type 1 diabetes. At baseline and 6-year follow-up, a detailed structured clinical interview was conducted to document medical history including kidney dialysis or transplant, other diabetic complications, and renal-specific mortality. Plasma levels of 28 inflammatory biomarkers were measured using a multiplex bead analysis system. After adjusting for baseline age, glycohemoglobin and other confounders, the baseline plasma levels of intercellular adhesion molecule-1(s-ICAM-1) in the upper two quartiles were respectively associated with a 3 to 5-fold increases in the risk of progression from none or microalbuminuria to overt proteinuria. Baseline plasma levels of the chemokine eotaxin in the upper quartile were significantly associated with a 7-fold increase in risk of incident renal failure. These associations were independent of traditional risk factors for progression of diabetic nephropathy. Thus, in type 1 diabetic African Americans, s-ICAM-1 predicted progression to overt proteinuria and eotaxin predicted progression to renal failure.

Factors Affecting Clinical Depression in Diabetic Geriatric Population

Introduction: Diabetes mellitus is a common metabolic disorder affecting about 10% - 25% of the elderly population. The mechanisms, linking diabetes and major depressive disorders are unknown. Obesity is the risk factor for both diabetes mellitus and depression. The goal of this study was to explore if BMI of elderly diabetic patients with depression differed from BMI of the diabetic individuals without depression. Further, we aimed to explore the association of age, gender, health insurance status, ethnicity influence and systolic blood pressure (SBP) and diastolic blood pressure (DBP) with clinical depression in geriatric diabetics. Methods: Nursing home residents were recruited from an outpatient internal medicine clinic in a teaching university setting. After given written consent, patients received Public Health Questionnaire-9 (PHQ-9) in either English or Spanish language. Results: While the clinically depressed diabetic participants did not differ from that of the non-depressed diabetic participants with respect to age (70.6 ± 6.1 vs. 72.1 ± 4.8; p = 0.111), gender (47.2% of males vs. 57.1% of females; p = 0.754), or ethnicity (69% explain vs. 71%, p = 1.000), race did appear to differ in depression status: Caucasian, African-American, and others were respectively 37%, 48%, and 15% vs. 32%, 16%, 52%, p = 0.0003). Neither the BMI (p > 0.499) nor Hemoglobin A1c (p > 0.839) differed between the clinically depressed and non-depressed participants when controlled for these race differences. Conclusion: In our sample, diabetic African Americans are three times more likely to be depressed. Diabetic Caucasians also experience higher rates of clinical depression. However, diabetics with depression did not differ from diabetics without depression with regard to their age, gender, BMI, HbA1C, health insurance status, systolic blood pressure or diastolic blood pressure.

Global Gene Expression Profiling in Omental Adipose Tissue of Morbidly Obese Diabetic African Americans.

Adipose tissues play important role in the pathophysiology of obesity-related diseases including type 2 diabetes (T2D). To describe gene expression patterns and functional pathways in obesity-related T2D, we performed global transcript profiling of omental adipose tissue (OAT) in morbidly obese individuals with or without T2D. Twenty morbidly obese (mean BMI: about 54 kg/m2) subjects were studied, including 14 morbidly obese individuals with T2D (cases) and 6 morbidly obese individuals without T2D (reference group). Gene expression profiling was performed using the Affymetrix U133 Plus 2.0 human genome expression array. Analysis of covariance was performed to identify differentially expressed genes (DEGs). Bioinformatics tools including PANTHER and Ingenuity Pathway Analysis (IPA) were applied to the DEGs to determine biological functions, networks and canonical pathways that were overrepresented in these individuals. At an absolute fold-change threshold of 2 and false discovery rate (FDR) < 0.05, 68 DEGs were identified in cases compared to the reference group. Myosin X (MYO10) and transforming growth factor beta regulator 1 (TBRG1) were upregulated. MYO10 encodes for an actin-based motor protein that has been associated with T2D. Telomere extension by telomerase (HNRNPA1, TNKS2), D-myo-inositol (1, 4, 5)-trisphosphate biosynthesis (PIP5K1A, PIP4K2A), and regulation of actin-based motility by Rho (ARPC3) were the most significant canonical pathways and overlay with T2D signaling pathway. Upstream regulator analysis predicted 5 miRNAs (miR-320b, miR-381-3p, miR-3679-3p, miR-494-3p, and miR-141-3p,) as regulators of the expression changes identified. This study identified a number of transcripts and miRNAs in OAT as candidate novel players in the pathophysiology of T2D in African Americans.

APOL1 associations with nephropathy, atherosclerosis, and all-cause mortality in African Americans with type 2 diabetes

Albuminuria and reduced eGFR associate with two apolipoprotein L1 gene (APOL1) variants in non-diabetic African Americans. Whether APOL1 associates with subclinical atherosclerosis and survival remains unclear. To determine this, 717 African American-Diabetes Heart Study participants underwent computed tomography to determine coronary artery, carotid artery, and aorta calcified atherosclerotic plaque mass scores in addition to the urine albumin:creatinine ratio (UACR), eGFR, and C-reactive protein. Associations between mass scores and APOL1 were assessed adjusting for age, gender, African ancestry, BMI, HbA1c, smoking, hypertension, use of statins and ACE inhibitors, albuminuria, and eGFR. Participants were 58.9% female with mean age 56.5 years, eGFR 89.5 ml/min/1.73m2, UACR 169.6 mg/g, coronary artery, carotid artery and aorta calcified plaque mass scores of 610, 171 and 5378, respectively. In fully adjusted models, APOL1 risk variants were significantly associated with lower levels of carotid artery calcified plaque (β −0.42, SE 0.18, dominant model), and marginally lower coronary artery plaque (β −0.36, SE 0.21; dominant model), but not with aorta calcified plaque, C-reactive protein, UACR, or eGFR. After a mean follow-up of 5.0 years, 89 participants died. APOL1 nephropathy risk variants were significantly associated with improved survival (hazard ratio 0.67 for 1 copy; 0.44 for 2 copies). Thus, APOL1 nephropathy variants associate with lower levels of subclinical atherosclerosis and reduced risk of death in African Americans with type 2 diabetes mellitus.

Montreal Cognitive Assessment and Modified Mini Mental State Examination in African Americans.

Background. Sparse data limit the interpretation of Montreal Cognitive Assessment (MoCA) scores, particularly in minority populations. Additionally, there are no published data on how MoCA scores compare to the widely used Modified Mini Mental State Examination (3MSE). We provide performance data on the MoCA in a large cohort of African Americans and compare 3MSE and MoCA scores, providing a “crosswalk” for interpreting scores. Methods. Five hundred and thirty African Americans with type 2 diabetes were enrolled in African American-Diabetes Heart Study-MIND, a cross-sectional study of cognition and structural and functional brain imaging. After excluding participants with possible cognitive impairment (n = 115), mean (SD) MoCA and 3MSE scores are presented stratified by age and education. Results. Participant mean age was 58.2 years (range: 35-83); 61% were female; and 64.9% had >12 years of education. Mean (SD) 3MSE and MoCA scores were 86.9 (8.2) and 19.8 (3.8), respectively. 93.5% of the cohort had a “positive” screen on the MoCA, scoring <26 (education-adjusted), compared with 47.5% on the 3MSE (cut-point < 88). A 3MSE score of 88 corresponded to a MoCA score of 20 in this population. Conclusion. The present data suggest the need for caution when applying proposed MoCA cutoffs to African Americans.

Type 2 Diabetes and Cognitive Decline Over 14 Years in Middle-Aged African Americans and Whites: The ARIC Brain MRI Study

Background: Diabetes predicts late-life dementia, but the association with rate of cognitive decline is inconsistent and has rarely been examined in non-white populations, despite the high prevalence of diabetes in African Americans. We evaluated the effect of diabetes on cognitive decline in middle-aged African Americans and whites. Methods: Atherosclerosis Risk in Communities (ARIC) Brain MRI Study participants (n = 1,886, mean age = 60, 49% African American) underwent assessments of verbal memory, processing speed, and verbal fluency four times over 14 years. Using race-stratified mixed linear effects models, we examined cognitive change for participants with prevalent (baseline) diabetes and incident (diagnosed after baseline) diabetes versus those without diabetes. Results: African Americans had more advanced diabetes, as indicated by fasting blood glucose levels, anti-diabetes medication use, and cardiovascular risk profiles. African Americans with prevalent diabetes experienced 41% greater annual decline in processing speed scores (p = 0.048) and 50% greater annual decline in verbal fluency scores (p = 0.042) than those without diabetes; incident diabetes was not associated with cognitive decline. Among whites, diabetes was not associated with cognitive decline. Conclusions: Prevalent diabetes was associated with greater cognitive decline in middle-aged African Americans, possibly reflecting adverse effects of longer duration and more advanced diabetes. i 2014 S. Karger AG, Basel

Kidney Disease and Cognitive Function: African American-Diabetes Heart Study MIND

Aims: Albuminuria and reduced estimated glomerular filtration rate (eGFR) are linked with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were performed in unrelated AAs with T2D to determine relationships. Methods: Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol. Results: Participants had a mean ± SD age of 60.2 ± 9.7 years, 62.7% were female, T2D duration was 14.3 ± 8.9 years, eGFR 86.0 ± 23.2 ml/min/1.73 m², and UACR 155.8 ± 542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p = 0.014), MoCA (p = 0.0089), DSC (p = 0.0004), Stroop performance time (p = 0.003), Stroop errors (p = 0.032), and Stroop interference (p = 0.026). Higher eGFR was associated with better performance on DSC (p = 0.0071). Conclusions: In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.

Cerebral Structural Changes in Diabetic Kidney Disease: African American–Diabetes Heart Study MIND

OBJECTIVEAlbuminuria and reduced kidney function are associated with cognitive impairment. Relationships between nephropathy and cerebral structural changes remain poorly defined, particularly in African Americans (AAs), a population at higher risk for both cognitive impairment and diabetes than European Americans. We examined the relationship between urine albumin:creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and cerebral MRI volumes in 263 AAs with type 2 diabetes.RESEARCH DESIGN AND METHODSCross-sectional associations between renal parameters and white matter (WM), gray matter (GM), hippocampal, and WM lesion (WML) volumes were assessed using generalized linear models adjusted for age, education, sex, BMI, hemoglobin A1c (HbA1c) level, and hypertension.RESULTSParticipants had a mean (SD) age of 60.2 years (9.7 years), and 62.7% were female. Mean diabetes duration was 14.3 years (8.9 years), HbA1c level was 8.2% (2.2%; 66 mmol/mol), eGFR was 86.0 mL/min/1.73 m2 (23.2 mL/min/1.73 m2), and UACR was 155.8 mg/g (542.1 mg/g; median 8.1 mg/g). Those with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2 or UACR >30 mg/g) had smaller GM and higher WML volumes. Higher UACR was significantly associated with higher WML volume and greater atrophy (larger cerebrospinal fluid volumes), and smaller GM and hippocampal WM volumes. A higher eGFR was associated with larger hippocampal WM volumes. Consistent with higher WML volumes, participants with CKD had significantly poorer processing speed and working memory. These findings were independent of glycemic control.CONCLUSIONSWe found albuminuria to be a better marker of cerebral structural changes than eGFR in AAs with type 2 diabetes. Relationships between albuminuria and brain pathology may contribute to poorer cognitive performance in patients with mild CKD.

Personal Health Record Design Preferences for Minority Diabetic Patients

Facilitating treatment adherence (diet, exercise, medication, self-management technology use) among patients with a chronic disease poses a significant challenge to health care providers, particularly among minority populations. Racial and ethnic minorities experience higher rates of chronic disease prevalence and mortality and lower rates of health literacy, which has been widely linked to inferior health care quality. Health Information Technology (HIT) is a critical component of chronic disease treatment and has the ability to support patient self-management through the use of a Personal Health Record (PHR). However, current PHR systems are not designed for the largest and highest-risk segment of the chronic disease population, which are minorities. In an effort to address racial and ethnic disparities in PHRs, this research aims to evaluate minority design preferences in the patient population, develop a design database, and develop several design alternatives for use in future PHR testing and implementation. In this pilot, we focused on one of the highest risk chronic disease populations, African American diabetics. Data was collected from the Howard University Hospital Diabetes Treatment Center, using a previously launched patient portal as a baseline for all research activities. This research has the potential to inform PHR vendor design decision-making and future regulatory guidelines for HIT.

Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15×10−94<P<5×10−8, odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2×10−23 < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.