The Journal of Steroid Biochemistry and Molecular Biology
Vitamin D and diabetes☆
Introduction
Diabetes, a chronic condition associated with serious morbidity, increased mortality and accelerated health care costs, is rapidly becoming a global epidemic. The total number of people with diabetes worldwide is expected to rise from 171 million in 2000 to 366 million by 2030 [1]. Although the majority of new cases are due to type 2 diabetes, the incidence of type 1 diabetes has been increasing as well. The growing incidence and prevalence of diabetes highlights the need for innovative approaches for the management and prevention of the disease. Epidemiologic data suggest that 9 out of 10 cases of type 2 diabetes could be attributed to modifiable habits and lifestyle [2]; however, lifestyle changes are difficult to achieve and maintain long term. Much less is known about modifiable risk factors for type 1 diabetes. Therefore, identification of modifiable risk factors for prevention of both types of diabetes is needed. Recently, there has been increasing evidence from animal and human studies, to suggest that vitamin D may play a role in modifying risk of diabetes [3].
Section snippets
Potential mechanisms of action of vitamin D on glucose metabolism
Type 1 diabetes is due to autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency. For type 2 diabetes to develop, impaired pancreatic beta-cell function, insulin resistance and systemic inflammation are often present. There are several lines of evidence to support that vitamin D influences all these pathways [3].
A role for vitamin D in pancreatic beta-cell function might be mediated by the binding of circulating 1,25-dihydroxyvitamin D to the beta-cell vitamin D
Observational studies for type 1 diabetes
Vitamin D insufficiency has long been suspected to be a risk factor for type 1 diabetes. Indirect evidence comes from studies that have reported higher incidence and prevalence of type 1 diabetes in countries at higher latitude compared to counties at lower latitude [5]. There is also seasonal variation in the birth date of patients who subsequently develop type 1 diabetes, with risk increasing with births in the spring-summer months, which suggest an effect of lower sunshine in utero [6]. Type
Observational studies for type 2 diabetes
Several cross-sectional studies have examined the association between vitamin D status and prevalence of glucose intolerance or type 2 diabetes. Although most have reported an inverse association between vitamin D status and glucose intolerance, others failed to show such an association (studies reviewed by Pittas et al. [3]).
Two longitudinal cohort studies from the US and one study from Finland (which analyzed two separate cohorts) have reported an association between vitamin D status and risk
Summary of evidence from the human studies on type 1 and 2 diabetes
Although cross-sectional studies have reported relatively consistent associations between low vitamin D status and prevalent type 1 or type 2 diabetes [3], [26], the evidence from longitudinal observational studies is sparse and inconclusive and, therefore, definite conclusions cannot be drawn for a variety of reasons: recall bias in the case-control studies in type 1 diabetes when the predictor (vitamin D status) was ascertained by recall years after the diagnosis of diabetes, considerable
Optimal intake of vitamin D in relation to diabetes
The optimal vitamin D intake and 25OHD concentration is currently hotly debated and there is growing consensus that vitamin D intakes above the current recommendations may be associated with better health outcomes. In the US, currently recommended intakes for vitamin D are 400 IU/day for those aged 51–70 years and 600 IU/day for those aged >70 years [27] but these intakes are currently under review by the US Institute of Medicine. Based on the available studies reviewed here, it is difficult to
Conclusions and future directions
An inverse association between vitamin D status and both types of diabetes is suggested by observational studies. However, the lack of large prospective observational studies that have measured 25(OH)D as the exposure variable prior to ascertainment of the outcome and the lack of randomized trials specifically designed to test the effects of vitamin D on diabetes limits drawing any definitive conclusions. To better define the clinical role of vitamin D as a potential intervention for prevention
Acknowledgements
Funded by NIH Research grants R01DK76092 and R01DK79003 (to AGP, funded by the National Institute of Diabetes and Digestive and Kidney Disease, and the NIH Office of Dietary Supplements), R21DK78867 (to AGP, funded by the National Institute of Diabetes and Digestive and Kidney Disease) and US Department of Agriculture Agreement 58-1950-9001 (to BDH).
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Special issue selected article from the 14th Vitamin D Workshop held at Brugge, Belgium on October 4–8, 2009.