Weight Loss and Vitamin D Improve Hyporesponsiveness to Corticosteroids in Obese Asthma.

BACKGROUND AND OBJECTIVES: Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss. METHODS: The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 [51-59] years), 14 nonobese asthma patients (NOA) (11 females; 53 [43-60] years), 15 obese patients (OP) (13 females; 47 [45-60] years), and 19 healthy controls (HC) (14 females; 43 [34-56] years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2. RESULTS: We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP1 expression in OP and OA. CONCLUSION: The efficacy of weight loss to improve symptoms and lung function in OA may be due, at least in part, to the recovered anti-inflammatory effects of corticosteroids. Vitamin D deficiency may contribute to corticosteroid hyporesponsiveness in OA.

Evening chronotype associates with obesity in severely obese subjects: interaction with CLOCK 3111T/C.

BACKGROUND: Chronotype has been related to obesity and metabolic disturbances. However, little is known about the relationship between circadian preferences and genetic background in CLOCK genes with obesity and weight loss among severely obese patients after bariatric surgery. OBJECTIVES: The research goals were (1) to examine whether evening chronotype is related to obesity and weight loss evolution in severely obese followed during 6 years after bariatric surgery and (2) to examine potential interactions between circadian preferences and CLOCK 3111T/C for obesity in this population. SUBJECTS/METHODS: Participants (n=252, 79% female; age (mean±s.d.): 52±11 years; body mass index (BMI): 46.4±6.0 kg m-2) were grouped into evening and morning types. Obesity and weight loss parameters, energy and macronutrients intake, energy expenditure, chronotype, meal timing, sleep duration and CLOCK genotype were studied. RESULTS: Evening-type subjects showed significantly higher initial body weight (P=0.015) and BMI (P=0.014) than morning types. Moreover, evening-type, when compared with morning types, lost less weight (percentage of excess weight loss) after bariatric surgery (P=0.015). Weight-loss progression between the two chronotype groups differed significantly from the fourth year after the bariatric surgery toward a higher weight regain among evening types (P<0.05). We also detected a significant interaction between CLOCK 3111T/C SNP and chronotype for body weight at baseline (P<0.001). Specifically, among carriers of the risk allele C, evening types showed higher body weight than morning types (P=0.012). In addition, CLOCK 3111T/C SNP significantly associated with obesity and sleep duration in the older subjects. CONCLUSIONS: Evening chronotype is associated with higher obesity in severely obese subjects and with lower weight loss effectiveness after bariatric surgery. In addition, circadian preferences interact with CLOCK 3111T/C for obesity. The circadian and genetic assessment could provide tailored weight loss recommendations in subjects who underwent bariatric surgery.

Timing of food intake is associated with weight loss evolution in severe obese patients after bariatric surgery.

BACKGROUND: Recent research has demonstrated a relationship between the timing of food intake and weight loss in humans. However, whether the meal timing can be associated with weight loss in patients treated with bariatric surgery is unknown. OBJECTIVE: To evaluate the role of food-timing in the evolution of weight loss in a sample of 270 patients that underwent bariatric surgery with a follow-up of 6 years. METHODS: Participants (79% women; age [mean ± SD]: 52 ± 11 years; BMI: 46.5 ± 6.0 kg/m2) were classified according their weight loss response patterns after bariatric surgery: good weight-loss-responders (67.8%), primarily poor weight-loss-responders (10.8%) or secondarily poor weight-loss-responders (21.4%). Then, they were grouped in early-eaters and late-eaters, according to the timing of the main meal (before or after 15:00 h). Obesity and biochemical parameters, energy and macronutrients intake, energy expenditure, sleep duration, and chronotype were studied. RESULTS: The percentage of late eaters (after 15:00 h) was significantly higher in the primarily poor weight-loss-responders (∼70%) than in both secondarily poor weight-loss-responders (∼42%) and good weight-loss-responders (∼37%) (p = 0.011). Consistently, primarily poor weight-loss-responders had lunch later as compared to good and secondarily poor weight-loss-responders (p = 0.034). Age, gender and type of surgery were not determining. Surprisingly, obesity-related variables, biochemical parameters, pre-surgical total energy expenditure, sleep duration, chronotype, calorie intake and macronutrients distribution, were similar among groups. CONCLUSIONS: Weight loss effectiveness after bariatric surgery is related to the timing of the main meal. Our preliminary results suggest that the timing of food intake is important for weight regulation and that eating at the right time may be a relevant factor to consider in weight loss therapy even after bariatric surgery.

Systemic and immune manifestations in myelodysplasia: a multicenter retrospective study.

OBJECTIVE: The presence of systemic and/or immune manifestations in myelodysplasia has been currently reported. The influence of these manifestations on the natural outcome of myelodysplastic syndrome has to be considered. We present a multicenter retrospective study (2002-2009) of patients with myelodysplastic syndrome disclosing systemic and/or immune manifestations. METHODS: Forty-six patients with myelodysplasia presenting with systemic and/or immune manifestations were compared in terms of survival with 189 patients with myelodysplasia lacking these features. RESULTS: The clinical picture in these cases consisted of fever (13%), arthralgia or arthritis (13%), and cutaneous manifestations (67%). Four cases of systemic vasculitis have been reported in our series, and they have a worse prognosis. Immune anomalies were recorded in 29% of the cases, and the presence of cryoglobulins was also associated with a worse prognosis. CONCLUSION: A difference in survival between patients with myelodysplastic syndrome with systemic manifestations and patients lacking these manifestations has been observed in the presence of systemic vasculitis and/or cryoglobulins.