Depletion of circulating progenitor cells precedes overt diabetes: A substudy from the VA enhanced fitness trial

BackgroundOne theory of aging and disease development is that chronic injury (pathology) results in activation of regenerative processes and initial repair, with overt disease arising only after exhaustion of reparative capability leads to inadequate repair. While depletion of circulating progenitor cells (CPCs) has been noted in diabetes, the degree to which CPC depletion predates and is associated with propensity to develop overt disease is unclear.MethodsThe Enhanced Fitness trial enrolled overweight/obese (body mass index > 25) sedentary patients with glucose intolerance but without overt diabetes. Baseline CPCs were measured in 129 patients based on the cell surface markers CD34, CD133, and aldehyde dehydrogenase (ALDH) activity. HgbA_1C, fasting insulin and glucose levels, and HOMA calculations were ascertained.ResultsLower counts of early angiogenic CPCs identified as CD34⁺, CD34⁺CD133⁺, and ALDH-bright (ALDH^br) cells were associated with impairments in glucose homeostasis as reflected by HgbA_1C, but not fasting insulin, glucose, or HOMA-IR. These associations remained when corrected for age and cardiovascular risk factors.Conclusions/InterpretationThe numbers of CD34⁺ and ALDH^br CPCs were significantly lower in patients with impaired glucose tolerance. Depletion of reparative capacity as reflected by loss of CPCs may presage overt disease as exemplified in this pre-diabetes model.     

The Association Between Obstructive Sleep Apnea and Hypertension by Race/Ethnicity in a Nationally Representative Sample

The association between obstructive sleep apnea (OSA) and hypertension by race/ethnicity has not been well characterized in a national sample. Adult participants in the 2007–2008 National Health and Nutrition Examination Survey were reviewed by self‐report of sleep apnea diagnosis, snorting, gasping or stopping breathing during sleep, and snoring to derive whether OSA was probable (pOSA). Multivariable logistic regression determined whether pOSA predicted hypertension in the overall cohort, and by body mass index (BMI) group and ethno‐racial strata. pOSA predicted hypertension in several groups: (1) Within BMI strata, there was a significant association among overweight individuals [odds ratio [OR], 1.82; 95% confidence interval [CI], 1.26–2.62); (2) In race/ethnicity subgroups, the association was significant among Hispanic/Latinos (OR, 1.69; 95% CI, 1.13–2.53) and whites (OR, 1.40; 95% CI, 1.07–1.84); (3) In models stratified by both race/ethnicity and BMI, pOSA predicted hypertension among overweight black/African Americans (OR, 4.74; 95% CI, 1.86–12.03), overweight whites (OR, 1.65; 95% CI, 1.06–2.57), and obese Hispanic/Latino participants (OR, 2.01; 95% CI, 1.16–3.49). A simple, self‐report tool for OSA was strongly associated with hypertension, and may serve as a potential future opportunity for OSA diagnosis.     

Toward the Operationalization and Examination of “Hitting Bottom” for Problematic Alcohol Use: A Literature Review

“Hitting bottom” among individuals with alcohol use disorders (AUDs) has empirical and theoretical support; however, it has never been operationalized and, therefore, remains largely unexplored. To operationalize and evaluate hitting bottom, it is important to understand the emergence of the construct, how it is used by researchers, and how it is perceived by individuals recovering from AUDs. Accordingly, the authors review extant literature on hitting bottom for individuals with AUDs. Specifically, the authors discuss historical evolution of “hitting bottom” to inform future research efforts to operationalize and evaluate the concept of hitting bottom for individuals with problematic alcohol use.     

Antibody levels correlate with detection of Trypanosoma cruzi DNA by sensitive polymerase chain reaction assays in seropositive blood donors and possible resolution of infection over time

BACKGROUND: The clinical significance of anti‐Trypanosoma cruzi low‐level reactive samples is incompletely understood. Polymerase chain reaction (PCR)‐positive rates and antibody levels among seropositive blood donors in three countries are described. STUDY DESIGN AND METHODS: Follow‐up samples were collected from T. cruzi–seropositive donors from 2008 through 2010 in the United States (n = 195) and Honduras (n = 58). Also 143 samples from Brazil in 1996 to 2002, originally positive by three serologic assays, were available and paired with contemporary follow‐up samples from these donors. All samples were retested with Ortho enzyme‐linked immunosorbent assay (ELISA). PCR assays were performed on coded sample panels by two laboratories (Blood Systems Research Institute [BSRI] and American Red Cross Holland Laboratory [ARC]) that amplified kinetoplast minicircle DNA sequences of T. cruzi. RESULTS: PCR testing at BSRI yielded slightly higher overall sensitivity and specificity (33 and 98%) compared with those at the ARC (28 and 94%). Among seropositive donors, PCR‐positive rates varied by country (p < 0.0001) for the BSRI laboratory: Brazil (57%), Honduras (32%), and the United States (14%). ELISA signal‐to‐cutoff ratios (S/CO) were significantly higher for PCR‐positive compared to PCR‐negative donors (p < 0.05 for all comparisons). Additionally, PCR‐negative Brazilian donors exhibited greater frequencies of antibody decline over time versus PCR‐positive donors (p = 0.003). CONCLUSION: For all three countries, persistent DNA positivity correlated with higher ELISA S/CO values, suggesting that high‐level seroreactivity reflects chronic parasitemia. Significant S/CO declines in 10% of the PCR‐negative Brazilian donors may indicate seroreversion after parasite clearance in the absence of treatment.