Specialized High�Protein Oral Nutrition Supplement Improves Home Nutrient Intake of Malnourished Older Adults Without Decreasing Usual Food Intake

Background: Reduced nutrient intake is common in patients after hospitalization, contributing to increased risk for readmissionand mortality. Oral nutrition supplements can improve nutrition status and clinical outcomes, but intake of food is prioritized byclinicians. This study examines the impact of a high-protein oral nutrition supplement (S-ONS) on nutrient intake post discharge. Methods: In a subset of patients (14 S-ONS and 16 placebo) from the NOURISH (Nutrition effect On Unplanned ReadmIssionsand Survival in Hospitalized patients) trial, 24-hour dietary recalls were conducted on 3 randomly selected days during the weeksof 30, 60, and 90 days post discharge. Nutrient intake was estimated using Nutrition Data System for Research software. Adequateenergy and protein intake were dened as 30 kcal/kg/d and 1.2 g/kg/d, respectively. Dietary Reference Intakes (DRIs) were usedfor other nutrients. Results: Less than half of patients met the requirements for energy, protein, and 12 micronutrients from foodintake alone during the study. Energy and protein intakes from food were not diminished relative to placebo. Considering nutrientintake from both food and S-ONS, 50% and 71% of patients receiving S-ONSs met energy and protein goals respectively at 90 days(compared with 29% and 36%, in the placebo group), and 100% met the DRI for total carbohydrate, iron, phosphorus, copper,selenium, thiamin, and riboavin at all time points, all of which were consumed at higher amounts vs placebo. Conclusion: Threemonths of S-ONS consumption increases intake of numerous nutrients without decreasing nutrient intake from food in oldermalnourished adults post discharge

Spontaneous Weight Change during Chronic Hepatitis C Treatment: Association with Virologic Response Rates

Objective: We examined weight changes during chronic hepatitis C (CHC) therapy and association with virologic response. Methods: Weight changes were compared between subjects achieving rapid, early, and sustained virologic response rates (RVR, EVR, and SVR). RVR, EVR and SVR were compared among patients with or without weight loss of ≥ 0.5 body mass index (BMI) units (kg/m2) at 4, 12, 48 weeks. Results: CHC therapy was initiated in 184 cases. Median pretreatment BMI was 27.7 (18.4-51.3) with 38% overweight and 31% obese (BMI ≥25 and ≥ 30, respectively). Among patients with liver biopsies (n = 90), steatosis was present in 31.6%; fibrosis grade of 1-2/6 in 46%, 3-4 in 37.3% and 5-6 in 14.7%. Mean weight loss at 4, 12, 24 and 48 weeks of therapy were 1.2, 2.6, 3.8 and 3.3 kg, respectively. After 4 and 12 weeks of treatment, 38% and 54.3% had a BMI decrement of ≥ 0.5 kg/m2. For genotype 1, weight loss at 4 weeks was associated with significantly higher EVR (90.0% vs. 70%, p = 0.01) and a tendency towards better RVR and SVR (42.9% vs. 26.0% and 55.2% vs. 34.8%, respectively, p = 0.08). In multivariate analysis, weight loss at 4 weeks was independently associated with EVR (OR 6.3, p = 0.02) but was not significantly associated with RVR or SVR Conclusions: Spontaneous weight loss at 4 and 12 weeks of CHC therapy was associated with improved EVR. Weight loss at 4 weeks was an independent predictor of EVR but not SVR

Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial

SummaryBackgroundHospitalized, malnourished older adults have a high risk of readmission and mortality.ObjectiveEvaluation of a high-protein oral nutritional supplement (HP-HMB) containing beta-hydroxy-beta-methylbutyrate on postdischarge outcomes of nonelective readmission and mortality in malnourished, hospitalized older adults.DesignMulticenter, randomized, placebo-controlled, double-blind trial.SettingInpatient and posthospital discharge.PatientsOlder (≥65 years), malnourished (Subjective Global Assessment [SGA] class B or C) adults hospitalized for congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease.InterventionsStandard-of-care plus HP-HMB (n = 328) or a placebo supplement (n = 324), 2 servings/day.MeasurementsPrimary composite endpoint was 90-day postdischarge incidence of death or nonelective readmission. Other endpoints included 30- and 60-day postdischarge incidence of death or readmission, length of stay (LOS), SGA class, body weight, and activities of daily living (ADL).ResultsThe primary composite endpoint was similar between HP-HMB (26.8%) and placebo (31.1%). No between-group differences were observed for 90-day readmission rate, but 90-day mortality was significantly lower with HP-HMB relative to placebo (4.8% vs. 9.7%; relative risk 0.49, 95% confidence interval [CI], 0.27 to 0.90; p = 0.018). The number-needed-to-treat to prevent 1 death was 20.3 (95% CI: 10.9, 121.4). Compared with placebo, HP-HMB resulted in improved odds of better nutritional status (SGA class, OR, 2.04, 95% CI: 1.28, 3.25, p = 0.009) at day 90, and an increase in body weight at day 30 (p = 0.035). LOS and ADL were similar between treatments.LimitationsLimited generalizability; patients represent a selected hospitalized population.ConclusionsAlthough no effects were observed for the primary composite endpoint, compared with placebo HP-HMB decreased mortality and improved indices of nutritional status during the 90-day observation period.Clinical trial registrationwww.ClinicalTrials.gov NCT01626742

Serotonin transporter (SERT) and translocator protein (TSPO) expression in the obese ob/ob mouse

Background: An ever growing body of evidences is emerging concerning metabolism hormones, neurotransmitters or stress-related biomarkers as effective modulators of eating behavior and body weight in mammals. The present study sought at examining the density and affinity of two proteins related to neurotransmission and cell metabolism, the serotonin transporter SERT and the cholesterol import-benzodiazepine site TSPO (translocator protein), in a rodent leptin-lacking mutant, the obese ob/ob mouse. Binding studies were thus carried out in brain or peripheral tissues, blood platelets (SERT) and kidneys (TSPO), of ob/ob and WT mice supplied with a standard diet, using the selective radiochemical ligands [(3)H]-paroxetine and [(3)H]-PK11195. Results: We observed comparable SERT number or affinity in brain and platelets of ob/ob and WT mice, whilst a significantly higher [(3)H]-PK11195 density was reported in the brain of ob/ob animals. TSPO binding parameters were similar in the kidneys of all tested mice. By [(3)H]-PK11195 autoradiography of coronal hypothalamic-hippocampal sections, an increased TSPO signal was detected in the dentate gyrus (hippocampus) and choroids plexus of ob/ob mice, without appreciable changes in the cortex or hypothalamic-thalamic regions. Conclusions: These findings show that TSPO expression is up-regulated in cerebral regions of ob/ob leptin-deficient mice, suggesting a role of the translocator protein in leptin-dependent CNS trophism and metabolism. Unchanged SERT in mutant mice is discussed herein in the context of previous literature as the forerunner to a deeper biochemical investigation

Metabolic Regulation in Progression to Autoimmune Diabetes

Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes