Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes.

OBJECTIVE: Leptin therapy improves insulin sensitivity in people with leptin deficiency, but it is not known whether it improves insulin action in people who are not leptin deficient. The purpose of the current study was to determine whether leptin treatment has weight loss-independent effects on insulin action in obese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a randomized, placebo-controlled trial in obese subjects (BMI: 35.4 ± 0.6 kg/m(2); mean ± SE) with newly diagnosed type 2 diabetes. Subjects were randomized to treatment with placebo (saline), low-dose (30 mg/day), or high-dose (80 mg/day) recombinant methionyl human (r-Met hu) leptin for 14 days. Multiorgan insulin sensitivity before and after treatment was evaluated by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusions to measure glucose, glycerol, and fatty acid kinetics. RESULTS: Low-dose and high-dose leptin treatment resulted in a threefold (P < 0.01) and 150-fold (P < 0.001) increase in basal plasma leptin concentrations, respectively. However, neither low-dose nor high-dose therapy had an effect on insulin-mediated suppression of glucose, glycerol, or palmitate rates of appearance into plasma compared with placebo. In addition, leptin treatment did not increase insulin-mediated stimulation of glucose disposal compared with placebo (14.3 ± 3.1, 18.4 ± 3.6, 16.7 ± 2.4 vs. 17.5 ± 2.5, 20.7 ± 3.0, 19.1 ± 3.3 µmol/kg body wt/min before vs. after treatment in the placebo, low-dose, and high-dose leptin groups, respectively). CONCLUSIONS: r-Met hu leptin does not have weight loss-independent, clinically important effects on insulin sensitivity in obese people with type 2 diabetes.

Prevalence of anemia in skilled-nursing home residents.

Anemia is a frequent problem among older persons, the prevalence of which may be particularly high in skilled-nursing facilities but recent data in this regard is lacking. The purpose of this study was to define the prevalence of anemia and its association with hospitalization in skilled-nursing home residents. We retrospectively reviewed randomly selected charts among five skilled-nursing facilities within the National Geriatrics Research Consortium (NGRC). Among 900 chronically residing patients with completed chart information, the mean and median ages were 79 years and 82 years, respectively. Eighty-seven percent of patients were 65 years or greater. Applying the World Health Organization criteria for anemia (hemoglobin <12 g/dl for women and hemoglobin <13 g/dl for men), we found a 6-month point prevalence of 48%. The hospitalization rate was higher among those with more severe anemia. Few residents were treated with recombinant erythropoietin therapy or red blood cell transfusion. Anemia is very common in the nursing home, and despite being associated with increased morbidity; it is, for the most part, untreated in this setting. With an increased understanding of erythropoiesis and the availability of recombinant growth factors, future studies should evaluate the causes and potential benefits of treatment in terms of quality of life, reduced morbidity and health economics.

Anemia and its relationship to clinical outcome in heart failure.

BACKGROUND: Anemia is often observed in patients with chronic heart failure (CHF), but its implications for patient outcomes are not well understood. The goal of this study was to investigate the relationship between anemia, severity of CHF, and clinical outcomes. METHODS AND RESULTS: Hemoglobin concentration (Hb) was measured in 912 subjects with CHF enrolled in the Randomized Etanercept North American Strategy to Study Antagonism of Cytokines (RENAISSANCE) trial. In a subgroup of 69 subjects, cardiac MRI was performed at randomization and 24 weeks later. Anemia (Hb < or =12.0 g/dL) was present in 12% of subjects. Cox regression analysis indicated that for every 1-g/dL-higher baseline Hb, the risk of mortality was 15.8% lower (P=0.0009) and the risk of mortality or hospitalization for heart failure was 14.2% lower (P<0.0001). Greater CHF severity was associated with significantly lower Hb concentrations. An increase in Hb over time was associated with a decrease in left ventricular mass and lower mortality, whereas a decrease in Hb over time was associated with an increase in left ventricular mass and higher mortality. In multivariate analysis, anemia remained a significant, independent predictor of death or hospitalization for heart failure, with both outcomes being significantly higher in all NYHA classes. CONCLUSIONS: Anemia is frequently present in patients with CHF. Lower Hb is associated with greater disease severity, a greater left ventricular mass index, and higher hospitalization and mortality rates.

Mechanisms of unexplained anemia in the nursing home.

OBJECTIVES: To characterize anemia in elderly nursing home residents. DESIGN: Prospective multiinstitutional cohort study. SETTING: Five nursing homes. PARTICIPANTS: From retrospective analysis, residents found to be anemic using chart review were prospectively randomized. Of the 81 residents enrolled, 60 were anemic. MEASUREMENTS: Chart review for medical history and factors related to treatment or history of anemia, extensive laboratory evaluation for causes of anemia, and classification of anemia by two hematologists. RESULTS: Among the 60 anemic residents, the causes of anemia were idiopathic (n=27), iron-deficiency (n=14), anemia associated with chronic disease (n=8), anemia of renal insufficiency (n=6), and other (n=5). The eryrthropoietin (EPO) response to anemia was lower in residents with idiopathic anemia (IA) than in those with iron-deficiency anemia, and this correlated with renal function as estimated using calculated creatinine clearance. In this elderly population, advancing age was not correlated with lower EPO response. CONCLUSION: IA is common in nursing home residents. A lower EPO response contributes to the high prevalence of anemia in this setting and may be due, in part, to occult renal dysfunction.