Publications

In progressive familial intrahepatic cholestasis type 2 (PFIC-2), severe steatorrhea is often documented. However, pancreatic exocrine secretion has not yet been studied. In 14 children with PFIC-2, pancreatic function was assessed using standard fecal tests. Normal fecal lipase concentrations excluded isolated lipase deficiency. No differences in fecal elastase-1 concentrations and chymotrypsin activities were detected between PFIC-2 patients with or without steatorrhea, nor between these patients and healthy subjects. In conclusion, pancreatic exocrine function in patients with PFIC-2 is normal. Steatorrhea observed in those patients is not related to pancreatic insufficiency.

OBJECTIVES

To determine whether the failure of the orexigenic hormone ghrelin to increase as it normally does with weight loss contributes to impaired weight recovery in older persons.

DESIGN

Prospective diet intervention study.

SETTING

University of Washington Medical Center from 2001 through 2005.

PARTICIPANTS

Twenty-one younger (18-35) and 18 older (> or =70) men and women.

INTERVENTION

Two weeks of a weight-maintaining diet were followed in sequence by 2 weeks of 30% calorie restriction, then 4 weeks of ad libitum food intake.

MEASUREMENTS

Twenty-four-hour plasma ghrelin levels, dual x-ray absorptiometry scan for body composition, resting energy expenditure, and calorie intakes were measured.

RESULTS

Both younger and older subjects lost weight with calorie restriction and failed to fully regain their baseline weight. The older adults trended toward increasing their calorie intake above their baseline level during the ad libitum period (111+/-66 kcal, P=.11), whereas the younger individuals did not (-236+/-95 kcal, P=.02). There was no statistically significant difference between the two cohorts in 24-hour ghrelin levels before or after calorie restriction. Ghrelin levels in the two cohorts increased equivalently after calorie restriction and decreased after ad libitum food consumption resumed.

CONCLUSION

Ghrelin levels in healthy older individuals respond appropriately in a compensatory manner to changes in body weight and calorie intake.

OBJECTIVE

Although prior research demonstrated that improving diabetes self-efficacy can improve self-management behavior, little is known about the applicability of this research across race/ethnicity and health literacy levels. We examined the relationship between diabetes self-efficacy and self-management behavior in an urban, diverse, low-income population with a high prevalence of limited health literacy.

RESEARCH DESIGN AND METHODS

We administered an oral questionnaire in Spanish and English to patients with type 2 diabetes at two primary care clinics at a public hospital. We measured self-efficacy, health literacy, and self-management behaviors using established instruments. We performed multivariate regressions to explore the associations between self-efficacy and self-management, adjusting for clinical and demographic factors. We tested for interactions between self-efficacy, race/ethnicity, and health literacy on self-management.

RESULTS

The study participants were ethnically diverse (18% Asian/Pacific Islander, 25% African American, 42% Latino/a, and 15% white), and 52% had limited health literacy (short version of the Test of Functional Health Literacy in Adults score <23). Diabetes self-efficacy was associated with four of the five self-management domains (P < 0.01). After adjustment, with each 10% increase in self-efficacy score, patients were more likely to report optimal diet (0.14 day more per week), exercise (0.09 day more per week), self-monitoring of blood glucose (odds ratio 1.16), and foot care (1.22), but not medication adherence (1.10, P = 0.40). The associations between self-efficacy and self-management were consistent across race/ethnicity and health literacy levels.

CONCLUSIONS

Self-efficacy was associated with self-management behaviors in this vulnerable population, across both race/ethnicity and health literacy levels. However, the magnitude of the associations suggests that, among diverse populations, further study of the determinants of and barriers to self-management is warranted. Policy efforts should be focused on expanding the reach of self-management interventions to include ethnically diverse populations across the spectrum of health literacy.

Among individuals receiving highly active antiretroviral therapy (HAART), injection drug users (IDUs) are less likely to achieve HIV suppression. The present study examined individual-level, interpersonal, and structural factors associated with achieving undetectable plasma viral load (UVL) among US IDUs receiving recommended HAART. Data were from baseline assessments of the INSPIRE (Interventions for Seropositive Injectors-Research and Evaluation) study, a 4-site, secondary HIV prevention intervention for heterosexually active IDUs. Of 1113 study participants at baseline, 42% (n = 466) were currently taking recommended HAART (34% were female, 69% non-Hispanic black, 26% recently homeless; median age was 43 years), of whom 132 (28%) had a UVL. Logistic regression revealed that among those on recommended HAART, adjusted odds of UVL were at least 3 times higher among those with high social support, stable housing, and CD4 > 200; UVL was approximately 60% higher among those reporting better patient-provider communication. Outpatient drug treatment and non-Hispanic black race and an interaction between current drug use and social support were marginally negatively significant. Among those with high perceived support, noncurrent drug users compared with current drug users had a greater likelihood of UVL; current drug use was not associated with UVL among those with low support. Depressive symptoms (Brief Symptom Inventory) were not significant. Results suggest the major role of social support in facilitating effective HAART use in this population and suggest that active drug use may interfere with HAART use by adversely affecting social support. Interventions promoting social support functioning, patient-provider communication, stable housing, and drug abuse treatment may facilitate effective HAART use in this vulnerable population.

An alpha1-adrenergic receptor (alpha1-AR) antagonist increased heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), but it is unknown whether this adverse result was due to alpha1-AR inhibition or a nonspecific drug effect. We studied cardiac pressure overload in mice with double KO of the 2 main alpha1-AR subtypes in the heart, alpha 1A (Adra1a) and alpha 1B (Adra1b). At 2 weeks after transverse aortic constriction (TAC), KO mouse survival was only 60% of WT, and surviving KO mice had lower ejection fractions and larger end-diastolic volumes than WT mice. Mechanistically, final heart weight and myocyte cross-sectional area were the same after TAC in KO and WT mice. However, KO hearts after TAC had increased interstitial fibrosis, increased apoptosis, and failed induction of the fetal hypertrophic genes. Before TAC, isolated KO myocytes were more susceptible to apoptosis after oxidative and beta-AR stimulation, and beta-ARs were desensitized. Thus, alpha1-AR deletion worsens dilated cardiomyopathy after pressure overload, by multiple mechanisms, indicating that alpha1-signaling is required for cardiac adaptation. These results suggest that the adverse cardiac effects of alpha1-antagonists in clinical trials are due to loss of alpha1-signaling in myocytes, emphasizing concern about clinical use of alpha1-antagonists, and point to a revised perspective on sympathetic activation in heart failure.