17
views
0
recommends
+1 Recommend
2 collections
    0
    shares

          The flagship journal of the Society for Endocrinology. Learn more

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A pilot interventional study to evaluate the impact of cholecalciferol treatment on HbA1c in type 1 diabetes (T1D)

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Higher 25(OH)D3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c.

          Aims

          (1) To assess the baseline 25(OH)D3 status in a Manchester cohort of children with type 1 diabetes (T1D). (2) To determine the effect of cholecalciferol administration on HbA1c.

          Methods

          Children with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OH)D3 level <50 nmol/L were treated with a one-off cholecalciferol dose of 100,000 (2–10 years) or 160,000 (>10 years) units. HbA1c levels before and after treatment were recorded.

          Results

          Vitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OH)D3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1c ( r = −0.484, P < 0.01). In treated participants, there was no significant difference in mean HbA1c at 3 months ( t = 1.010, P = 0.328) or at 1 year ( t = −1.173, P = 0.248) before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level.

          Conclusion

          We report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities.

          Type 1 and type 2 diabetes are characterized by progressive beta-cell failure. Apoptosis is probably the main form of beta-cell death in both forms of the disease. It has been suggested that the mechanisms leading to nutrient- and cytokine-induced beta-cell death in type 2 and type 1 diabetes, respectively, share the activation of a final common pathway involving interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and Fas. We review herein the similarities and differences between the mechanisms of beta-cell death in type 1 and type 2 diabetes. In the insulitis lesion in type 1 diabetes, invading immune cells produce cytokines, such as IL-1beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. IL-1beta and/or TNF-alpha plus IFN-gamma induce beta-cell apoptosis via the activation of beta-cell gene networks under the control of the transcription factors NF-kappaB and STAT-1. NF-kappaB activation leads to production of nitric oxide (NO) and chemokines and depletion of endoplasmic reticulum (ER) calcium. The execution of beta-cell death occurs through activation of mitogen-activated protein kinases, via triggering of ER stress and by the release of mitochondrial death signals. Chronic exposure to elevated levels of glucose and free fatty acids (FFAs) causes beta-cell dysfunction and may induce beta-cell apoptosis in type 2 diabetes. Exposure to high glucose has dual effects, triggering initially "glucose hypersensitization" and later apoptosis, via different mechanisms. High glucose, however, does not induce or activate IL-1beta, NF-kappaB, or inducible nitric oxide synthase in rat or human beta-cells in vitro or in vivo in Psammomys obesus. FFAs may cause beta-cell apoptosis via ER stress, which is NF-kappaB and NO independent. Thus, cytokines and nutrients trigger beta-cell death by fundamentally different mechanisms, namely an NF-kappaB-dependent mechanism that culminates in caspase-3 activation for cytokines and an NF-kappaB-independent mechanism for nutrients. This argues against a unifying hypothesis for the mechanisms of beta-cell death in type 1 and type 2 diabetes and suggests that different approaches will be required to prevent beta-cell death in type 1 and type 2 diabetes.
            • Record: found
            • Abstract: found
            • Article: not found

            Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis.

            To assess whether vitamin D supplementation in infancy reduces the risk of type 1 diabetes in later life. This was a systematic review and meta-analysis using Medline, Embase, Cinahl, Cochrane Central Register of Controlled Trials and reference lists of retrieved articles. The main outcome measure was development of type 1 diabetes. Controlled trials and observational studies that had assessed the effect of vitamin D supplementation on risk of developing type 1 diabetes were included in the analysis. Five observational studies (four case-control studies and one cohort study) met the inclusion criteria; no randomised controlled trials were found. Meta-analysis of data from the case-control studies showed that the risk of type 1 diabetes was significantly reduced in infants who were supplemented with vitamin D compared to those who were not supplemented (pooled odds ratio 0.71, 95% CI 0.60 to 0.84). The result of the cohort study was in agreement with that of the meta-analysis. There was also some evidence of a dose-response effect, with those using higher amounts of vitamin D being at lower risk of developing type 1 diabetes. Finally, there was a suggestion that the timing of supplementation might also be important for the subsequent development of type 1 diabetes. Vitamin D supplementation in early childhood may offer protection against the development of type 1 diabetes. The evidence for this is based on observational studies. Adequately powered, randomised controlled trials with long periods of follow-up are needed to establish causality and the best formulation, dose, duration and period of supplementation.
              • Record: found
              • Abstract: found
              • Article: found

              Global Consensus Recommendations on Prevention and Management of Nutritional Rickets

              Background: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. Evidence: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. Process: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. Results: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. Conclusion: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                May 2017
                05 April 2017
                : 6
                : 4
                : 225-231
                Affiliations
                [1 ]Division of Developmental Biology & Medicine School of Medical Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK
                [2 ]Department of Biochemistry Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
                [3 ]Department of Paediatric Endocrinology Royal Manchester Children’s Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester, UK
                [4 ]Department of General Paediatrics Royal Manchester Children’s Hospital, Central Manchester Foundation Hospitals NHS Trust, Manchester, UK
                Author notes
                Correspondence should be addressed to P E Clayton; Email: peter.clayton@ 123456manchester.ac.uk
                Article
                EC170045
                10.1530/EC-17-0045
                5632717
                28381562
                a6a95506-7b59-4fd7-af5c-e24364501b09
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 19 March 2017
                : 5 April 2017
                Categories
                Research

                diabetes,bone,paediatric endocrinology,vitamin d,hba1c
                diabetes, bone, paediatric endocrinology, vitamin d, hba1c

                Comments

                Comment on this article

                Related Documents Log