Effect of vitamin D supplementation on glycaemic control and insulin resistance: A systematic review and meta-analysis

Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Diabetic Medicine (Impact Factor: 3.12). 04/2012; 29(8):e142-50. DOI: 10.1111/j.1464-5491.2012.03672.x
Source: PubMed


To systematically review the evidence for the effect of vitamin D supplementation on glycaemia, insulin resistance, progression to diabetes and complications of diabetes.
Systematic review and meta-analysis. We searched databases including MEDLINE, EMBASE and the Cochrane Library for randomized controlled trials comparing vitamin D or analogues with placebo. We extracted data on fasting glucose, glycaemic control, insulin resistance, insulin/C-peptide levels, micro- and macrovascular outcomes and progression from non-diabetes to diabetes. Studies were assessed independently by two reviewers according to a pre-specified protocol.
Fifteen trials were included in the systematic review. Trial reporting was of moderate, variable quality. Combining all studies, no significant improvement was seen in fasting glucose, HbA(1c) or insulin resistance in those treated with vitamin D compared with placebo. For patients with diabetes or impaired glucose tolerance, meta-analysis showed a small effect on fasting glucose (-0.32 mmol/l, 95%CI -0.57 to -0.07) and a small improvement in insulin resistance (standard mean difference -0.25, 95%CI -0.48 to -0.03). No effect was seen on glycated haemoglobin in patients with diabetes and no differences were seen for any outcome in patients with normal fasting glucose. Insufficient data were available to draw conclusions regarding micro- or macrovascular events; two trials failed to show a reduction in new cases of diabetes in patients treated with vitamin D.
There is currently insufficient evidence of beneficial effect to recommend vitamin D supplementation as a means of improving glycaemia or insulin resistance in patients with diabetes, normal fasting glucose or impaired glucose tolerance.

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    • "However, controlled supplementation trials with vitamin D or its analogues have not been able to produce similar results. In a recent systematic review and meta-analysis of 15 trials lasting from two months to 7 years, no significant improvements were seen in glucose homeostasis when all trials were included [3]. The results from the more recent trials have been inconsistent. "
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    ABSTRACT: Epidemiological evidence suggests a role for vitamin D in type 2 diabetes prevention. We investigated the effects of vitamin D3 supplementation on glucose metabolism and inflammation in subjects with prediabetes. A 5-month randomized, double-blind, placebo-controlled intervention with three arms (placebo, 40 μg/d, or 80 μg/d vitamin D3) was carried out among sixty-eight overweight (BMI 25-35) and aging (≥60 years) subjects from Finland, with serum 25-hydroxyvitamin D3 [25(OH)D3] < 75 nmol/L and either impaired fasting glucose or impaired glucose tolerance. Analyses included 66 subjects who completed the trial. Glucose metabolism was evaluated by fasting and 2-hour oral glucose tolerance test-derived indices and glycated hemoglobin. Inflammation was evaluated by high-sensitive C-reactive protein and five cytokines. Although a dose-dependent increase in serum 25(OH)D3 over the supplementation period was observed (P trend < 0.001), there were no other statistically significant differences in changes in the 13 glucose homeostasis indicators between the study groups other than increase in the 120 min glucose concentration (P trend = 0.021) and a decreasing trend both in 30 min plasma insulin (P trend = 0.030) and glycated hemoglobin (P trend = 0.024) concentrations. A borderline statistically significant decreasing trend in interleukin-1 receptor antagonist concentration was observed (P = 0.070). Vitamin D3 supplementation does not improve glucose metabolism in ageing subjects with prediabetes but may have modest anti-inflammatory effects.
    Full-text · Article · Jun 2015 · Journal of Diabetes Research
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    • "In view of the above findings, one can hypothesize that vitamin D supplementation decreases insulin resistance and reduces HbA1c levels in patients with diabetes. However, supplementation studies have not unambiguously found that vitamin D favors an improvement in glucose homeostasis parameters [9]. As it is well known that ageing and chronic kidney disease (CKD) are associated with changes in vitamin D metabolism and insulin resistance [10] [11], these studies would have been enriched by taking into account the impact of a number of factors on glucose metabolism, such as age, renal status, and antidiabetic medications but to name a few. "
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    ABSTRACT: Aim. To examine the relationship between plasma 25-hydroxyvitamin D (25(OH)D) levels and blood hemoglobin A1c (HbA1c) levels in diabetic patients at various stages of chronic kidney disease (CKD). Methods. We screened for data collected between 2003 and 2012. The correlation between 25(OH)D and HbA1c levels was studied in patients categorized according to the severity of CKD and their vitamin D status. A multivariate linear regression model was used to determine whether 25(OH)D and HbA1c levels were independently associated after adjustment for a number of covariates (including erythrocyte metformin levels). Results. We identified 542 reports from 245 patients. The mean HbA1c value was % in vitamin D sufficiency, % in insufficiency, and % in deficiency (). There was a negative correlation between 25(OH)D and HbA1c levels for the population as a whole (, ) and in the CKD severity subgroups (, and , for CKD stages 1–3 and 4-5, resp.). In the multivariate analysis, the 25(OH)D level was the only factor associated with HbA1c (). Conclusion. 25(OH)D levels were negatively correlated with HbA1c levels independently of study covariates.
    Full-text · Article · Aug 2014 · International Journal of Endocrinology
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    • "We hope this study will give new insight into this causality. Until now conflicting results are seen in observational studies and the few clinical trials performed, which could not confirm a causal association [7-14]. Factors for the lack of effect found in these studies includes: short trial duration, relatively low doses of vitamin D supplementation whether or not combined with calcium supplements, and heterogeneous study populations. "
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    ABSTRACT: Background: Besides the classical role of vitamin D on calcium and bone homeostasis, vitamin D deficiency has recently been identified as a contributing factor in the onset of insulin resistance in type 2 diabetes mellitus. However, it is uncertain whether vitamin D deficiency and poor glycaemic control are causally interrelated or that they constitute two independent features of type 2 diabetes mellitus. There are limited clinical trials carried out which measured the effect of vitamin D supplementation on glycaemic control.The objective of this study is to investigate the effect of vitamin D supplementation on glycaemic control and quality of life in patients with type 2 diabetes mellitus. Methods/design: In a randomised double-blind placebo-controlled trial conducted in five general practices in the Netherlands three hundred patients with type 2 diabetes mellitus treated with lifestyle advises or metformin or sulphonylurea-derivatives are randomised to receive either placebo or 50,000 IU Vitamin D3 at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and six months. Secondary outcome measures include blood pressure, anthropometric parameters, lipid profile, insulin resistance, quality of life, advanced glycation end products and safety profiles. Quality of life will be measured by The Short Form (SF-36) Health Survey questionnaire. Advanced glycation end products are measured by an AGE-reader. Discussion: This trial will be the first study exploring the effect of vitamin D supplementation on both glycaemic control and quality of life in patients with type 2 diabetes mellitus. Our findings will contribute to the knowledge of the relationship between vitamin D status and insulin resistance in patients with type 2 diabetes mellitus. Trial registration: The Netherlands trial register: NTR3154.
    Full-text · Article · Jul 2014 · BMC Endocrine Disorders
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