Faculty Bibliography

BACKGROUND:SUDOSCAN® non-invasively measures peripheral small fiber and autonomic nerve activity using electrochemical skin conductance. Since neuropathy and nephropathy are microvascular Type 2 diabetes (T2D) complications, relationships between skin conductance, estimated glomerular filtration rate (eGFR), and urine albumin:creatinine ratio (UACR) were assessed. METHODS:Two hundred five African Americans (AA) with T2D, 93 AA non-diabetic controls, 185 European Americans (EA) with T2D, and 73 EA non-diabetic controls were evaluated. Linear models were fitted stratified by population ancestry and T2D, adjusted for covariates. RESULTS:Relative to EA, AA had lower skin conductance (T2D cases p<0.0001; controls p<0.0001). Skin conductance was also lower in T2D cases vs. controls in each population (p<0.0001, AA and EA). Global skin conductance was significantly associated with eGFR in AA and EA with T2D; adjusting for age, gender, BMI, and HbA1c, positive association was detected between skin conductance and eGFR in AA T2D cases (parameter estimate 3.38, standard error 1.2; p=5.2E(-3)), without association in EA T2D cases (p=0.22). CONCLUSIONS:Noninvasive measurement of skin conductance strongly associated with eGFR in AA with T2D, replicating results in Hong Kong Chinese. SUDOSCAN® may prove useful as a low cost, non-invasive screening tool to detect undiagnosed diabetic kidney disease in populations of African ancestry.

CONTEXT/BACKGROUND:Bone mineral density (BMD) and calcified atherosclerotic plaque (CP) demonstrate inverse relationships. Sclerostin, an endogenous regulator of the Wnt pathway and bone formation, has been associated with impaired osteoblast activation and may play a role in vascular calcification. OBJECTIVE:Our objective was to assess the relationships between sclerostin, BMD, and CP. DESIGN/METHODS:Generalized linear models were fitted to test for associations between sclerostin, volumetric BMD (vBMD), and CP. PARTICIPANTS/METHODS:A targeted population of 450 unrelated African Americans (AAs) with type 2 diabetes (T2D) was 56% female with mean/SD/median age of 55.4/9.5/55.0 years and a diabetes duration of 10.3/8.2/8.0 years. MAIN OUTCOME MEASURES/METHODS:Plasma sclerostin, computed tomography-derived thoracic and lumbar vertebrae trabecular vBMD, coronary artery, carotid artery, and aortoiliac CP were measured. RESULTS:Plasma sclerostin was 1119/401/1040 pg/mL, thoracic vBMD was 206.3/52.4/204.8 mg/cm3, lumbar vBMD was 180.7/47.0/179.0 mg/cm3, coronary artery CP score was 284/648/13, carotid artery CP score was 46/132/0, and aortoiliac CP score was 1613/2910/282. Sclerostin levels were higher in men than women (P<.0001). Before and after adjusting for age, sex, body mass index, blood pressure, smoking, hemoglobin A1c, and low-density lipoprotein-cholesterol, plasma sclerostin levels were positively associated with thoracic and lumbar vertebrae vBMD (P<.0001). Sex-stratified analyses verified significant relationships in both men and women (both P<.001). Sclerostin was not associated with CP except for an inverse relationship with carotid CP in men (fully adjusted model, P=.03). CONCLUSIONS:In this cross-sectional study of AA men and women with T2D, circulating sclerostin was positively associated with vBMD in the spine in both sexes and inversely associated with carotid artery CP in men. Sclerostin may play a role in skeletal mineral metabolism in AA but fails to explain inverse relationships between BMD and CP.

PURPOSE:The purpose of this study is to describe (1) the receipt of diabetes self-management education (DSME) in a large, diverse cohort of US youth with type 1 diabetes (T1DM), (2) the segregation of self-reported DSME variables into domains, and (3) the demographic and clinical characteristics of youth who receive DSME. METHODS:Data are from the US population-based cohort SEARCH for Diabetes in Youth. A cross-sectional analysis was employed using data from 1273 youth <20 years of age at the time of diagnosis of T1DM. Clusters of 19 self-reported DSME variables were derived using factor analysis, and their associations with demographic and clinical characteristics were evaluated using polytomous logistic regression. RESULTS:Nearly all participants reported receiving DSME content consistent with "survival skills" (eg, target blood glucose and what to do for low or high blood glucose), yet gaps in continuing education were identified (eg, fewer than half of the participants reported receiving specific medical nutrition therapy recommendations). Five DSME clusters were explored: receipt of specific MNT recommendations, receipt of diabetes information resources, receipt of clinic visit information, receipt of specific diabetes information, and met with educator or nutritionist. Factor scores were significantly associated with demographic and clinical characteristics, including race/ethnicity, socioeconomic status, and diabetes self-management practices. CONCLUSIONS:Health care providers should work together to address reported gaps in DSME to improve patient care.

AIMS/OBJECTIVE: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 m(2), 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.

OBJECTIVE:To estimate the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in a pilot study among youth participating in the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS/METHODS:DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI) (examination for foot abnormalities, distal vibration perception, and ankle reflexes). An MNSI exam (MNSIE) score >2 is diagnostic for DPN. RESULTS:The MNSIE was completed in 399 subjects, including 329 youth with type 1 diabetes (mean age 15.7 ± 4.3 years, duration 6.2 ± 0.9 years) and 70 with type 2 diabetes (mean age 21.6 ± 4.1 years, duration 7.6 ± 1.8 years). Glycated hemoglobin (A1C) was similar in both groups (8.8 ± 1.8% for type 1 vs. 8.5 ± 2.9% for type 2). The prevalence of DPN was significantly higher in youth with type 2 compared with those with type 1 diabetes (25.7 vs. 8.2%; P < 0.0001). In unadjusted analyses, diabetes type, older age, longer duration of diabetes, increased waist circumference, elevated blood pressure, lower HDL cholesterol, and presence of microalbuminuria (urinary albumin-to-creatinine ratio >30 mg/g) were associated with DPN. The association between diabetes type and DPN remained significant after adjustment for age and sex (odds ratio 2.29 [95% CI 1.05-5.02], P = 0.03). CONCLUSIONS:DPN prevalence among youth with type 2 diabetes approached rates reported in adult populations with diabetes. Our findings suggest not only that youth with diabetes are at risk for DPN but also that many already show measurable signs of DPN.

Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This article provides evidence in support of differential allele frequency distributions that underlie the higher rates of nondiabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biological factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The present era of precision medicine will couple one's genetic makeup with specific therapies to reduce rates of disease based on the presence of disease-specific alleles.

Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.

OBJECTIVES/OBJECTIVE:To examine whether the types of medical nutrition therapies (MNTs) taught to and used by youth with type 1 diabetes (T1D) vary by sociodemographic characteristics and cardiovascular (CVD) risk factors. DESIGN/METHODS:Cross-sectional study. SETTING/METHODS:The SEARCH for Diabetes in Youth study is a population-based cohort of individuals with clinical diagnosed diabetes. PARTICIPANTS/METHODS:A total of 1,191 individuals with T1D. MAIN OUTCOME MEASURES/METHODS:Types of MNTs and frequency of use. ANALYSIS/METHODS:Bivariate analysis and multivariate linear regression (P < .05) RESULTS: More race/ethnic minorities (vs whites), individuals with parents with less than a high school education (vs high school or higher education), and overweight/obese (vs underweight/normal weight) were taught additional MNTs. For underweight/normal weight individuals exclusively taught carbohydrate counting, those who used this approach "often" had lower hemoglobin A1c (8.6% vs 8.9%) and triglycerides (73.5 vs 84.1 mg/dL) than those who used it "sometimes/never." "Often" use of additional MNTs beyond carbohydrate counting was not associated with better mean values for CVD risk factors. CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:In individuals with T1D, race/ethnic minorities, individuals with parents with less than a high school education, and overweight/obese individuals are taught more MNTs. Further research is needed to understand the effectiveness of the various MNTs on CVD risk factors, and to identify how to translate nutrition knowledge to behavior and metabolic status.

Previous studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs) compared with European Americans (EAs). This finding might be attributable to the higher prevalence of cardiovascular disease (CVD) risk factors and poorer access to healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and good access to healthcare would have comparable or lower levels of WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and to test for association between WMH and race. The unadjusted mean WMH score from the Diabetes Heart Study-Mind was 1.9 in AAs and 2.3 in EAs (P = .3244). Among those with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9 in AAs and 3.9 in EAs (P = .0503). Adjustment for age and sex produced no statistically significant differences in WMH score between AAs and EAs. These independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden of WMH in AAs.

BACKGROUND:Cigarette smoking is the major cause of chronic obstructive pulmonary disease and emphysema. Recent studies suggest that susceptibility to cigarette smoke may vary by race/ethnicity; however, they were generally small and relied on self-reported race/ethnicity. OBJECTIVE:To test the hypothesis that relationships of smoking to lung function and per cent emphysema differ by genetic ancestry and self-reported race/ethnicity among Caucasians, African-Americans, Hispanics and Chinese-Americans. DESIGN/METHODS:Cross-sectional population-based study of adults age 45-84 years in the USA. MEASUREMENTS/METHODS:Principal components of genetic ancestry and continental ancestry estimated from one million genome-wide single nucleotide polymorphisms; pack-years of smoking; spirometry measured for 3344 participants; and per cent emphysema on computed tomography for 8224 participants. RESULTS:The prevalence of ever-smoking was: Caucasians, 57.6%; African-Americans, 56.4%; Hispanics, 46.7%; and Chinese-Americans, 26.8%. Every 10 pack-years was associated with -0.73% (95% CI -0.90% to -0.56%) decrement in the forced expiratory volume in 1 s to forced vital capacity (FEV1 to FVC) and a 0.23% (95% CI 0.08% to 0.38%) increase in per cent emphysema. There was no evidence that relationships of pack-years to the FEV1 to FVC, airflow obstruction and per cent emphysema varied by genetic ancestry (all p>0.10), self-reported race/ethnicity (all p>0.10) or, among African-Americans, African ancestry. There were small differences in relationships of pack-years to the FEV1 among male Chinese-Americans and to the FEV1 to FVC ratio with African and Native American ancestry among male Hispanics only. CONCLUSIONS:In this large cohort, there was little to no evidence that the associations of smoking to lung function and per cent emphysema differed by genetic ancestry or self-reported race/ethnicity.