RESUMO
Vitamin D deficiency is a common issue, particularly in obese populations, and is tested by assessing serum 25(OH)D concentrations. This study aimed to identify factors that contribute to the vitamin D status in fifty morbidly obese individuals recruited prior to bariatric surgery. Data collected included serum 25(OH)D concentrations, dietary and supplement intake of vitamin D, sun exposure measures, skin colour via spectrophotometry, and genotype analysis of several single nucleotide polymorphisms in the vitamin D metabolism pathway. Results showed a significant correlation between serum 25(OH)D concentrations and age, and serum 25(OH)D and ITAC score (natural skin colour). Natural skin colour accounted for 13.5% of variation in serum 25(OH)D, with every 10° increase in ITAC score (i.e., lighter skin) leading to a 9 nmol/L decrease in serum 25(OH)D. Multiple linear regression using age, ITAC score, and average UV index in the three months prior to testing, significantly predicted serum 25(OH)D concentrations (R² = 29.7%). Single nucleotide polymorphisms for all vitamin D genes tested, showed lower serum 25(OH)D for those with the rare genotype compared to the common genotype; this was most pronounced for fok1 and rs4588, where those with the rare genotype were insufficient (<50 nmol/L), and those with the common genotype were sufficient (≥50 nmol/L). Assessing vitamin D status in individuals with morbid obesity requires testing of 25(OH)D, but potential risk factors for this population include natural skin colour and age.
Assuntos
Índice de Massa Corporal , Obesidade Mórbida/sangue , Pigmentação da Pele , Luz Solar , Vitamina D/sangue , Estudos Transversais , Dieta , Comportamento Alimentar , Humanos , Inquéritos e QuestionáriosRESUMO
AIM: To assess the impact of vitamin D supplementation (cholecalciferol) on the insulin sensitivity and metabolic health of patients with chronic kidney disease (CKD). METHODS: Twenty-eight adult patients with CKD stages 3-4 were recruited from the outpatient department of the Princess Alexandra Hospital (Brisbane, Australia) to a double-blind randomized trial of cholecalciferol (vitamin D3) 2000 IU/day or placebo for 6 months. Metabolic parameters at baseline were compared with 20 non-CKD adults. The primary outcome was an improvement in insulin resistance (glucose disposal rate, GDR) at 6 months (quantified by hyperinsulinaemic euglycaemic clamp). Carbohydrate and lipid oxidation rates were assessed by indirect calorimetry. RESULTS: At baseline, patients were significantly insulin-resistant compared with lean younger non-CKD individuals (n = 9; GDR 3.42 vs. 5.76 mg/kg per minute, P = 0.001), but comparable with their age-, gender- and weight-matched non-CKD counterparts (n = 11; 3.42 vs. 3.98 mg/kg per minute, P = 0.4). 25-Hydroxyvitamin D did not change in the placebo group, but rose from 95 ± 37 to 146 ± 25 nmol/L with treatment (P = 0.0001). Post treatment, there was no difference in GDR between groups (GDR 3.38 vs. 3.52 mg/kg per minute, ancova P = 0.4). There was a relative increase in hyperinsulinaemic oxidative disposal of glucose with treatment (within-group P = 0.03). CONCLUSION: Supplementation with cholecalciferol in CKD 3-4 results in appreciable increases in 25-hydroxyvitamin D concentrations, but does not increase insulin sensitivity. The insulin resistance observed was similar among age-, sex- and body mass index-matched individuals with and without CKD. Whether renal dysfunction per se has any influence on the insulin sensitivity of an individual should be the subject of future work.
Assuntos
Colecalciferol/uso terapêutico , Resistência à Insulina , Doenças Metabólicas/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Vitaminas/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Doenças Metabólicas/etiologia , Insuficiência Renal Crônica/complicações , Índice de Gravidade de Doença , Falha de TratamentoRESUMO
Nutrapharmacology, or the use of bioactive food compounds at pharmacological doses is emerging as a therapeutic approach to target the complex metabolic dysregulations in ageing and obesity-related chronic disease. Resveratrol, a polyphenol found in the skin of grapes, and other edible plants and related food products, has received extensive attention through the link with the French paradox, and later with its chemopreventive activity demonstrated in vitro and in animal cancer models. A plethora of laboratory investigations has provided evidence for the multi-faceted properties of resveratrol and suggests that resveratrol may target ageing and obesity-related chronic disease by regulating inflammation and oxidative stress. A number of obstacles stand in the path to clinical usage however, not least the lack of clinical evidence to date, and the myriad of doses and formulations available. Further, data on the effects of resveratrol consumption in a capsule vs. food form is conflicting, and there are uncertain effects of long term dosing. The review will summarize the human pharmacokinetic and pharmacodynamic published data, and the topics for research if resveratrol is to become a multi-target therapeutic agent addressing chronic disease.
Assuntos
Antioxidantes/farmacocinética , Doença Crônica/prevenção & controle , Dieta , Estilbenos/farmacocinética , Envelhecimento/fisiologia , Antioxidantes/farmacologia , Suplementos Nutricionais , Alimentos , Humanos , Resveratrol , Estilbenos/farmacologiaRESUMO
BACKGROUND: Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation. METHODS/DESIGN: This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m(2); aged >or=18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1beta, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study. DISCUSSION: To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.