In this cross-sectional analysis of a population-based sample of septuagenarians, we found that the 25(OH)D3
concentration was inversely associated with the risk of newly diagnosed type 2 diabetes after adjustment for BMI and other established risk factors for type 2 diabetes. Subjects with 25(OH)D3
concentration below 50 nmol/L had the doubled risk of newly diagnosed diabetes compared with those having higher serum concentrations. Therefore, our data suggest an inverse association between the serum concentration of 25(OH)D3
and the odds of newly diagnosed type 2 diabetes, thereby suggesting a protective role of vitamin D against the development of the disease, as suggested previously (13
). In further support of this association, we observed an increasing concentration of HbA1c
with decreasing 25(OH)D3
concentration, and this association was independent of BMI, serum triacylglycerides, smoking status, and sex. Vitamin D deficiency showed a much weaker OR for type 2 diabetes previously diagnosed, as could perhaps have been anticipated, given the vigorous clinical management of the disease and the longer time interval between disease development and the assessment of vitamin D status. The confidence interval for the OR for the two groups of type 2 diabetes continues to overlap considerably, and therefore, the slight difference should not be overinterpreted ().
is considered an indicator of average blood glucose concentrations during the preceding 2 to 3 months and, thus, a long-term marker of glucose homeostasis (14
). Abnormalities may be a result of changes in insulin secretion and insulin-stimulated uptake of glucose in muscle and fat tissue. In vitro studies and laboratory animal studies suggest possible mechanisms for the effects of the active form of vitamin D, i.e., 1,25(OH)2
D, on both insulin secretion and insulin sensitivity as reviewed by Pittas and Dawson-Hughes (15
). For instance, in mice expressing a functionally inactive mutant vitamin D receptor, blood glucose concentrations were increased and serum insulin was reduced, as was insulin mRNA. Pancreatic β-cells express the vitamin D receptor and the enzyme 1-α-hydroxylase, thus suggesting that the active form of vitamin D has a functional role in these cells. Even though the current study cannot elucidate the likely mechanisms involved, our results appear highly plausible given the findings in experimental studies.
In this Faroese population of septuagenarians, 37% are obese (11
). Increased fat mass adversely influences glucose metabolism, in part by increasing insulin resistance, and is also linked with lower 25(OH)D concentrations in serum (16
). Therefore, we adjusted our data for BMI. The results suggest that the negative impact of vitamin D deficiency on HbA1c
and newly diagnosed type 2 diabetes risk is independent of increased fat mass. However, because BMI does not distinguish visceral from subcutaneous fat, some misclassification of adiposity may have occurred, thereby possibly causing some uncertainty in regard to the relative influence of serum 25(OH)D3
and adiposity in diabetes development.
Our study results are comparable with studies on vitamin D status and type 2 diabetes in younger populations (4
), and the current study extends this association to 70 years of age and older. Vitamin D status is known to be lower in the elderly compared with the young as the subcutaneous synthesis of vitamin D decreases with increasing age, due to a reduced concentration of 7-dehydrocholesterol in the skin (1
) and reduced absorption of oral vitamin D (8
). Hence, if the relationship between vitamin D status and glucose homeostasis is causal, the age-related decline in circulating concentration of 25(OH)D may augment the increase in risk of type 2 diabetes with age. In addition, our results suggest that this relationship is not the result of increased fish intake, in agreement with the existing, somewhat equivocal evidence in regard to this effect (21
). These differences may be a result of variations in fish intake to inherent differences in the populations examined and the study designs.
Among the strengths of our study, we examined a general population sample with a high prevalence of both vitamin D deficiency (11
) and type 2 diabetes. However, the current study is limited by its cross-sectional design and its single measurement of vitamin D status. Nonetheless, a recent study demonstrated excellent tracking and that the correlation of serum 25(OH)D3
concentrations sampled 14 years apart was similar to that seen for other cardiovascular risk factors and that most subjects with vitamin D deficiency were still deficient 14 years later (23
Patients with type 2 diabetes and elevated HbA1c
concentrations are at increased risk of cardiovascular disease and total mortality compared with patients with lower HbA1c
). Thus, clinical management focuses on glycemic control, including treatment of other modifiable cardiovascular risk factors to reduce the macro- as well as microvascular complications. The inverse association between serum 25(OH)D3
suggests that vitamin D supplementation could be considered a possible means for supporting glycemic control of type 2 diabetes. However, some intervention studies have shown inconclusive results on the effect of vitamin D on HbA1c
and type 2 diabetes (15
). For example, the Women Health’s Initiative demonstrated that daily supplementation with 10 µg of vitamin D3
for a median follow-up time of 7 years did not reduce the risk of type 2 diabetes in postmenopausal women (25
). However, the doses used were probably too low to bring about the necessary concentrations of circulating 25(OH)D3
. Therefore, further randomized clinical intervention studies are needed to elucidate the impact of vitamin D on the risk of type 2 diabetes.
In summary, our study extends previous findings that a high vitamin D status protects against type 2 diabetes in younger subjects to subjects older than 70 years. Likewise, our findings suggest an inverse association between HbA1c and 25(OH)D3 also in the elderly. Because our study has a cross-sectional design, formal confirmation requires intervention studies with appropriate doses to elucidate whether vitamin D supplementation could be used to counter the worldwide epidemic of type 2 diabetes. In this regard, the need to identify the necessary daily intake of vitamin D should include the possible effect on reducing the risk of type 2 diabetes, with special emphasis on the dietary needs of the elderly.