Circulating Vitamin D Metabolites and Kidney Disease in Type 1 Diabetes

Samuel Lunenfeld Research Institute (B.Z.), Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1X5
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 09/2012; 97(12). DOI: 10.1210/jc.2012-2852
Source: PubMed


Context:Impaired vitamin D metabolism may contribute to the development and progression of diabetic kidney disease.Objective:The aim of the study was to test associations of circulating vitamin D metabolites with risks of incident microalbuminuria, impaired glomerular filtration rate (GFR), and hypertension in type 1 diabetes.Design:We performed a cohort study of 1193 participants in the Diabetes Control and Complications Trial (DCCT), a randomized clinical trial of intensive diabetes therapy, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We measured plasma concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT and tested associations with incident microalbuminuria, impaired GFR, and hypertension over up to 16 yr of EDIC follow-up.Results:At the time metabolites were measured, mean age was 32.4 yr; mean duration of diabetes, 7.5 yr; mean iothalamate GFR, 132.9 ml/min/1.73 m(2); and geometric mean albumin excretion rate, 11.8 mg/24 h. Over follow-up, 166 cases of microalbuminuria, 54 cases of impaired GFR, and 541 cases of hypertension were observed. Compared with 25(OH)D of at least 30 ng/ml, 25(OH)D below 20 ng/ml was associated with a 65% higher risk of microalbuminuria (95% confidence interval, 7 to 154%) in adjusted analyses. Low concentrations of 24,25-dihydroxyvitamin D, but not 1,25-dihydroxyvitamin D, were also associated with increased risk of microalbuminuria. No circulating vitamin D metabolite was associated with risk of impaired GFR or hypertension.Conclusions:Low plasma concentrations of 25(OH)D and 24,25-dihydroxyvitamin D are associated with increased risk of microalbuminuria in type 1 diabetes. In contrast, we did not find evidence linking impaired vitamin D metabolism to early GFR loss or the development of hypertension.

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    • "This health claim is targeting men and women 60 years of age and older and the dose required is a daily consumption of 800 IU vitamin D, which can come from all sources. Further emerging vitamin D health relationships include physiological parameters like improved immune response (Baeke et al., 2010; Schwalfenberg, 2011; Hewison, 2012; White, 2012), improved respiratory health(Berry et al., 2011; Charan et al., 2012; Choi et al., 2013; Hirani, 2013) possibly also relate to reduced tuberculosis incidence (Nnoaham and Clarke, 2008; Martineau et al., 2011; Mitchell et al., 2011; Coussens et al., 2012; Salahuddin et al., 2013; Huaman et al., 2014); and reduced risk to develop autoimmune diseases like multiple sclerosis (Solomon and Whitham, 2010; Cantorna, 2012; Dobson et al., 2013) or type 1 diabetes (Hypponen et al., 2001; Holick, 2003; Ramos-Lopez et al., 2006; Baeke et al., 2010; De Boer et al., 2012; Dong et al., 2013; Van Belle et al., 2013). In chronic, non-communicable diseases, vitamin D deficiency is being discussed to possibly ameliorate the incidence of some neoplastic diseases like colorectal, lung, prostate, and breast cancers (Ng et al., 2008; Rosen et al., 2012; Welsh, 2012; Cheng et al., 2013); cardiovascular diseases (CVDs) including hypertension, myocardial infarction, stroke (Forman et al., 2007; Giovannucci et al., 2008; Gardner et al., 2011; Bischoff-Ferrari et al., 2012; Tamez and Thadhani, 2012; Karakas et al., 2013; Pilz et al., 2013a; Schroten et al., 2013); life-style diseases like obesity and type 2 diabetes (Pittas et al., 2007; González-Molero et al., 2012; Khan et al., 2013; Pilz et al., 2013b; Schottker et al., 2013; Tsur et al., 2013; Van Belle et al., 2013; Bouillon et al., 2014); diseases related to the decline in sight function including age-related macular degeneration (Parekh et al., 2007; Millen et al., 2011; Lee et al., 2012); and neurological disorders including Alzheimer and Parkinson disease (Buell and Dawson-Hughes, 2008; Annweiler et al., 2012; Eyles et al., 2013; Zhao et al., 2013). "
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    ABSTRACT: Vitamin D is a micronutrient that is needed for optimal health throughout the whole life. Vitamin D3 (cholecalciferol) can be either synthesized in the human skin upon exposure to the UV light of the sun, or it is obtained from the diet. If the photoconversion in the skin due to reduced sun exposure (e.g. in wintertime) is insufficient, intake of adequate vitamin D from the diet is essential to health. Severe vitamin D deficiency can lead to multitude of avoidable illnesses; among them are well known bone diseases like osteoporosis, a number of autoimmune diseases, many different cancers and some cardiovascular diseases like hypertension are being discussed. Vitamin D is found naturally in only very few foods. Foods containing vitamin D include some fatty fish, fish liver oils, and eggs from hens that have been fed vitamin D and some fortified foods in countries with respective regulations. Base on geographic location or food availability adequate vitamin D intake might not be sufficient on a global scale. The International Osteoporosis Foundation (IOF) has collected the 25-hydroxy-vitamin D plasma levels in populations of different countries using published data and developed a global vitamin D map. This map illustrates the parts of the world, where vitamin D did not reach adequate 25-hydroxyvitamin D plasma levels: 6.7 % of the papers report 25-hydroxyvitamin D plasma levels below 25 nmol/L, which indicates vitamin D deficiency, 37.3 % are below 50 nmol/Land only 11.9% found 25-hydroxy-vitamin D plasma levels above 75 nmol/L target as suggested by vitamin D experts. The vitamin D map is adding further evidence to the vitamin D insufficiency pandemic debate, which is also an issue in the developed world. Besides malnutrition, a condition where the diet does not match to provide the adequate levels of nutrients including micronutrients for growth and maintenance, we obviously have a situation where enough nutrients were consumed, but lacked to reach sufficient vitam
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    • "Moreover, participants with 25-hydroxyvitamin D levels <15 ng/mL had a 2.6-fold greater incidence of ESRD than those with levels ≥15 ng/mL during a long-term follow-up [19]. In addition, few studies demonstrated that low 25-hydroxyvitamin D levels were independently associated with albuminuria in CKD and type 1 diabetes, but they did not find evidence linking low concentrations of 25-hydroxyvitamin D to early GFR loss [20,21]. Thus, current data and our finding indicate that vitamin D deficiency/insufficiency is an extremely frequent condition in patients with CKD, especially those with an estimated GFR of less than 15 mL/min/1.73 "
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    ABSTRACT: Vitamin D insufficiency is associated with proteinuria and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined the significance of vitamin D insufficiency as a contributing factor for the development of ESRD in the Asian chronic kidney disease (CKD) population. Authors examined the relationship between vitamin D status and the staging of CKD using data from an outpatient clinic-based screening in 2,895 Thai CKD patients. Serum levels of 25-hydroxyvitamin D were analyzed according to CKD stages. Vitamin D deficiency and insufficiency were defined as a serum 25-hydroxyvitamin D concentration < 10 ng/mL and 10--30 ng/mL, respectively. The mean (SD) 25-hydroxyvitamin D levels were significantly lower according to severity of renal impairment (CKD stage 3a: 28.61+/-16.71 ng/mL, CKD stage 3b: 25.11+/-12.1 ng/mL, CKD stage 4 21.21+/-11.31 and CKD stage 5 18.84+/-9.01 ng/mL, p<0.001). The prevalence of vitamin D deficiency/insufficiency was from CKD stage 3a, 3b, 4 to 5, 66.6%, 70.9%, 74.6%, and 84.7% (p<0.001). The odds ratio (95% CI) of vitamin D insufficiency/deficiency (serum 25-hydroxyvitamin D <= 30 ng/mL) and vitamin D deficiency (serum 25-hydroxyvitamin D < 10 ng/mL) for developing ESRD, after adjustment for age, gender, hemoglobin, serum albumin, calcium, phosphate and alkaline phosphatase were 2.19 (95% CI 1.07 to 4.48) and 16.76 (95% CI 4.89 to 57.49), respectively. This study demonstrates that 25-hydroxyvitamin D insufficiency and deficiency are more common and associated with the level of kidney function in the Thai CKD population especially advanced stage of CKD.
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    • "The levels were lower during MS relapses than remission. [71] Type 1 diabetes mellitus de Boer et al. 2012 1193 / Low plasma concentrations of 25(OH)D and 24,25(OH) 2 D were associated with increased risk of microalbuminuria in T1DM. [79] Borkar et al. 2010 50 50 Plasma 25(OH)D levels were lower in T1DM children. "
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    ABSTRACT: Historically, vitamin D has been associated with the regulation of bone metabolism. However, increasing evidence demonstrates a strong association between vitamin D signaling and many biological processes that regulate immune responses. The discovery of the vitamin D receptor in multiple immune cell lineages, such as monocytes, dendritic cells, and activated T cells credits vitamin D with a novel role in modulating immunological functions and its subsequent role in the development or prevention of autoimmune diseases. In this review we, discuss five major areas in vitamin D biology of high immunological significance: (1) the metabolism of vitamin D; (2) the significance of vitamin D receptor polymorphisms in autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; (3) vitamin D receptor transcriptional regulation of immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells; (4) the prevalence of vitamin D insufficiency/deficiency in patients with multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; and finally, (5) the therapeutic effects of vitamin D supplementation on disease severity and progression.
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