RESUMEN
AIMS: To investigate the effect of short-term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes. METHODS: In a double-blind placebo-controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100,000 IU vitamin D2 (ergocalciferol) or 100,000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C-reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation. RESULTS: The mean [standard deviation (s.d.)] 25-hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: -0.05% [95% confidence interval (CI) -0.11, 0.02] or -0.51 mmol/mol (95% CI -1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI -0.04, 0.08) or 0.19 mmol/mol (95% CI -0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: -0.68 m/s (95% CI -1.31, -0.05); D3 versus placebo -0.73 m/s (95% CI -1.42, -0.03)]. No important safety issues were identified. CONCLUSIONS: Short-term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Colecalciferol/uso terapéutico , Diabetes Mellitus Tipo 2/prevención & control , Suplementos Dietéticos , Ergocalciferoles/uso terapéutico , 25-Hidroxivitamina D 2/sangre , Adulto , Anciano , Calcifediol/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Colecalciferol/administración & dosificación , Colecalciferol/efectos adversos , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Inglaterra/epidemiología , Ergocalciferoles/administración & dosificación , Ergocalciferoles/efectos adversos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Riesgo , Rigidez VascularAsunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Diabetes Mellitus/etiología , Neuropatías Diabéticas/prevención & control , Raquitismo/prevención & control , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/uso terapéutico , Biomarcadores/sangre , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/etiología , Angiopatías Diabéticas/prevención & control , Suplementos Dietéticos , Femenino , Historia del Siglo XVII , Historia del Siglo XX , Humanos , Masculino , Embarazo , Raquitismo/etiología , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
BACKGROUND: Vitamin-D deficiency and vitamin-D receptor genotype (VDR) are risk factors for several disorders with inflammatory components, including coronary heart disease (CHD) and diabetes, though the mechanisms involved are unclear. AIM: To examine the hypothesis that vitamin D status modulates the matrix metalloproteinase (MMP) system in a population with a high prevalence of vitamin D deficiency, a situation affecting susceptibility to CHD and diabetes. DESIGN: Prospective cross-sectional, interventional and embedded studies. METHODS: Circulating MMP2,9, the inhibitor TIMP-1 and C-reactive protein (CRP) were measured during studies of vitamin-D deficiency as a risk factor for type 2 diabetes and CHD in 171 healthy British Bangladeshi adults, free of known diabetes or major illness. Vitamin D status, VDR genotype, body-build, blood pressure, lipid and insulin profiles, glucose tolerance, fibrinogen, PAI-1, folate and homocysteine were measured. Vitamin-D-deficient subjects were re-assessed after 1 years' supplementation. MMP, TIMP-1 and CRP levels were measured in 41 subjects halfway through 5-year follow-up. Independent determinants of circulating concentrations of MMP9, TIMP-1 and CRP were assessed by multiple regression analysis. RESULTS: Vitamin D status was the sole determinant of circulating MMP9 (inversely) and an independent determinant of CRP (inversely). Determinants of TIMP-1 were MMP9, systolic blood-pressure (directly) and VDR genotype (TaqI). Significant reductions in MMP9 (-68%), TIMP-1 (-38%) and CRP (-23%) concentrations followed vitamin-D supplementation. DISCUSSION: Vitamin-D insufficiency is associated with increased circulating MMP2,9 and CRP, correctable by supplementation. This finding provides a possible mechanism for tissue damage in chronic inflammatory conditions, including CHD and diabetes.