Faculty Bibliography

AIMS/OBJECTIVE:To evaluate cardiovascular risk factors and heart rate variability (HRV) in young adults with type 2 diabetes and arterial stiffness and to explore the relationship between HRV and arterial stiffness. METHODS:We studied 185 young adults with youth-onset T2D enrolled in the SEARCH for Diabetes in Youth Study. Cardiovascular risk factors and HRV were compared between individuals with and without type 2 diabetes and arterial stiffness (defined as a pulse wave velocity greater than the 90th percentile of healthy controls, >6.767 m/s). Semiparametric regression evaluated the independent relationship between HRV and PWV. RESULTS:Participants with T2D and arterial stiffness were more likely to be older, non-Hispanic Black, have higher systolic and diastolic blood pressure, greater adiposity and obesity-related dyslipidemia (higher triglycerides and lower HDLC). Participants with T2D and arterial stiffness also had lower overall HRV (lower SDNN) with parasympathetic loss (lower RMSSD and PNN50), p < 0.05. Lower HRV tended to be but was not significantly associated with arterial stiffness after adjustment for age, race/ethnicity, sex and cardiovascular risk factors (beta coefficient = -1.11, p = 0.08). CONCLUSIONS:Youth with T2D and arterial stiffness have a worse cardiovascular risk profile, specifically risk factors related to the metabolic syndrome and lower HRV.

Introduction/UNASSIGNED:-nephropathy. Methods/UNASSIGNED:A global gene expression analysis was performed in human primary renal tubule cell lines derived from 50 African American individuals. Follow-up gene knock out, cell-based rescue, and microscopy experiments were performed. Results/UNASSIGNED:G0, G1, and G2 were created; G0 cells appeared to promote mitochondrial fusion, whereas G1 and G2 induced mitochondrial fission. The mitochondrial dynamic regulator Mdivi-1 significantly preserved cell viability and mitochondrial cristae structure and reversed mitochondrial fission induced by overexpression of G1 and G2. Conclusion/UNASSIGNED:-nephropathy.

BACKGROUND:"Energy drinks" are heavily marketed to the general public, across the age spectrum. The efficacy of decaffeinated energy drinks in enhancing subjective feelings of energy (s-energy) is controversial. OBJECTIVE:The authors sought to test the efficacy of the caffeine-free version of a popular energy drink compared with a placebo drink. METHODS:This study was a randomized, double-blind, placebo-controlled, crossover trial in 223 healthy men and women aged 18-70 y with intention-to-treat and completers analysis. Participants were randomly assigned to consumption of either the decaffeinated energy drink or a placebo drink on testing day 1, and the other drink a week later. A battery of computer-based mood and cognitive tests to assess s-energy was conducted at baseline and at 0.5, 2.5, and 5 h post-ingestion. The main outcome measures were 1) mood, which was assessed by using a General Status Check Scale and the Profile of Mood States 2nd edition brief form, and 2) cognitive measures, including the N-back task (reaction time and accuracy), Reaction Time test, Flanker task (distraction avoidance), and Rapid Visual Information Processing test. RESULTS:No statistically significant or meaningful benefits were observed for any outcome measure, including mood and cognitive measures. Analyses of mean differences, slopes, and median differences were consistent. CONCLUSIONS:No differences were detected across a range of mood/cognitive/behavioral/s-energy-level tests after consumption of the energy drink compared with a placebo drink in this diverse sample of adults. Thus, we found strong evidence that the energy drink is not efficacious in enhancing s-energy levels, nor any related cognitive or behavioral variables measured. In light of federal regulations, these findings suggest that labeling and marketing of some products which claim to provide these benefits may be unsubstantiated. This trial was registered at www.clinicaltrials.gov as NCT02727920.

Introduction/UNASSIGNED:genotypes. Methods/UNASSIGNED:APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. Results/UNASSIGNED:The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. Conclusion/UNASSIGNED:genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

Two renal-risk variants in the apolipoprotein L1 gene (APOL1) in African American (AA) deceased donors (DD) are associated with shorter renal allograft survival after transplantation. To identify additional genes contributing to allograft survival, a genome-wide association study was performed in 532 AA DDs. Phenotypic data were obtained from the Scientific Registry of Transplant Recipients. Association and single nucleotide polymorphism (SNP)-by-APOL1 interaction tests were conducted using death-censored renal allograft survival accounting for relevant covariates. Replication and inverse-variance weighted meta-analysis were performed using data from 250 AA DD in the Genomics of Transplantation study. Accounting for APOL1, multiple SNPs near the Nudix Hydrolase 7 gene (NUDT7) showed strong independent effects (p=1.6x10^-8 -2.2x10^-8 ). Several SNPs in the Translocation protein SEC63 homolog (SEC63; p=2x10^-9 -3.7x10^-8 ) and plasmacytoma variant translocation 1 (PVT1) genes (p=4.0x10^-8 -7x10^-8 ) modified the effect of APOL1 on allograft survival. SEC63 is expressed in human renal tubule cells and glomeruli and PVT1 is associated with diabetic kidney disease. Overall, associations were detected for 41 SNPs (p=2x10^-9 -5x10^-8 ) contributing independently or interacting with APOL1 to impact renal allograft survival after transplantation from AA DD. Given the small sample size of the discovery and replication sets, independent validations and functional genomic efforts are needed to validate these results.

Diabetes is one of the most common chronic diseases among persons aged <20 years (1). Onset of diabetes in childhood and adolescence is associated with numerous complications, including diabetic kidney disease, retinopathy, and peripheral neuropathy, and has a substantial impact on public health resources (2,3). From 2002 to 2012, type 1 and type 2 diabetes incidence increased 1.4% and 7.1%, respectively, among U.S. youths (4). To assess recent trends in incidence of diabetes in youths (defined for this report as persons aged <20 years), researchers analyzed 2002-2015 data from the SEARCH for Diabetes in Youth Study (SEARCH), a U.S. population-based registry study with clinical sites located in five states. The incidence of both type 1 and type 2 diabetes in U.S. youths continued to rise at constant rates throughout this period. Among all youths, the incidence of type 1 diabetes increased from 19.5 per 100,000 in 2002-2003 to 22.3 in 2014-2015 (annual percent change [APC] = 1.9%). Among persons aged 10-19 years, type 2 diabetes incidence increased from 9.0 per 100,000 in 2002-2003 to 13.8 in 2014-2015 (APC = 4.8%). For both type 1 and type 2 diabetes, the rates of increase were generally higher among racial/ethnic minority populations than those among whites. These findings highlight the need for continued surveillance for diabetes among youths to monitor overall and group-specific trends, identify factors driving these trends, and inform health care planning.

Background/UNASSIGNED:Although older adults encompass almost half of patients with advanced chronic kidney disease, it remains unclear which long-term hemodialysis vascular access type, arteriovenous fistula or arteriovenous graft, is optimal with respect to effectiveness and patient satisfaction. Clinical outcomes based on the initial AV access type have not been evaluated in randomized controlled trials. This pilot study tested the feasibility of randomizing older adults with advanced kidney disease to initial arteriovenous fistula versus graft vascular access surgery. Methods/UNASSIGNED:Patients 65 years or older with pre-dialysis chronic kidney disease or incident end-stage kidney disease and no prior arteriovenous vascular access intervention were randomized in a 1:1 ratio to undergo surgical placement of a fistula or a graft after providing informed consent. Trial feasibility was evaluated as (i) recruitment of ≥ 70% of eligible participants, (ii) ≥ 50 to 70% of participants undergo placement of index arteriovenous access within 90 to 180 days of enrollment, respectively, (iii) ≥ 80% adherence to study-related assessments, and (iv) ≥ 70% of participants who underwent index arteriovenous access placement will have a follow-up duration of ≥ 12 months after index surgery date. Results/UNASSIGNED:Between September 2018 and October 2019, 81% (44/54) of eligible participants consented and were enrolled in the study; 11 had pre-dialysis chronic kidney disease, and 33 had incident or prevalent end-stage kidney disease. After randomization, 100% (21/21) assigned to arteriovenous fistula surgery and 78% (18/23) assigned to arteriovenous graft surgery underwent index arteriovenous access placement within a median (1st, 3rd quartile) of 5.0 (1.0, 14.0) days and 13.0 (5.0, 44.3) days, respectively, after referral to vascular surgery. The completion rates for study-specific assessments ranged between 40.0 and 88.6%. At median follow-up of 215.0 days, 5 participants expired, 7 completed 12 months of follow-up, and 29 are actively being followed. Assessments of grip strength, functional independence, and vascular access satisfaction were completed by > 85% of patients who reached pre-specified post-operative assessment time point. Conclusions/UNASSIGNED:Results from this study reveal it is feasible to enroll and randomize older adults with advanced kidney disease to one of two different arteriovenous vascular access placement surgeries. The study can progress with minor protocol adjustments to a multisite clinical trial. Trial registration/UNASSIGNED:Clinical Trials ID, NCT03545113.

AIM:SEARCH has recently reported that both prevalence and incidence of youth onset type 2 diabetes (YT2D) increased among most US race/ethnic groups in the early 2000s. This study reports on the incidence (2002-2013) and prevalence (2001, 2009) of YT2D in the Navajo Nation among youth age < 20 years from 2001 to 2013. METHODS:SEARCH sought to identify prevalent YT2D cases in 2001 (N = 75) and 2009 (N = 70) and all incident YT2D cases in three periods: 2002 to 2005 (N = 53), 2006 to 2009 (N = 68), and 2010 2013 (N = 90) in Navajo Nation. Denominators were based on the active Indian Health Service user population for eligible health care facilities. Prevalence (per 100 000) and period-specific incidence rates (per 100 000 person-years) were computed for youth aged 10 to 19 years. Changes in prevalence were tested with a two-sided skew-corrected inverted score test, while changes in incidence were tested with Poisson regression. RESULTS:YT2D prevalence was high but stable in 2001 and 2009, overall [146.6 (116.8, 184.0) vs 141.5 (112.0, 178.8), P = .65) and in all subgroups. In contrast, incidence rates increased particularly between the second and third periods overall and in most subgroups by age and by sex. CONCLUSIONS:These data confirm the high burden of YT2D among Navajo youth and suggest an increasing risk in more recent years. However, recent improvements in obesity reduction in this population demonstrate optimism for potential reductions in YT2D in Navajo Nation.

BACKGROUND/OBJECTIVES:HtR) can better predict blood pressures and lipid parameters in youth. PARTICIPANTS/METHODS:HtR. RESULTS:HtR (p = 0.003), but otherwise comparisons between alternative WHtR protocols were not significantly different. CONCLUSIONS:Among youth with recently diagnosed diabetes, measurements of WHtR by either waist circumference protocol similarly helped estimate current and prospective cardiometabolic risk biomarkers.