We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2003–2006 and limited our analysis to the population ≥18 years old (⁶). We defined subjects as having diabetes if they answered yes to the question: “Have you ever been told by a doctor that you have diabetes?” or the subject reported current use of insulin or an oral antihyperglycemic medication (⁷).

Information about A1C measurements using boronate-affinity high-performance liquid chromatography, Diasorin RIA method for 25(OH)D measurement, and Elecsys parathyroid (PTH) immunoassay can be found on the NHANES Web site (⁸).

The association between A1C and 25(OH)D levels overall, by age-group and by reported history of diabetes is shown in Table 1. We observed an inverse association in the 35–74 year old group (P = 0.0045) after adjusting for multiple covariates. We did not detect a statistically significant association in the youngest age-group (18–34 years old) or the oldest age-group (≥75 years old). Of note, PTH levels and dietary supplement use were also negatively associated with A1C in the 35–74 year age-group (P = 0.0002, <0.0001, respectively). We also observed the inverse association between vitamin D and A1C levels in individuals who did not report a history of diabetes (P = 0.0282) but not among those with diabetes. We detected a statistically significant interaction between vitamin D status and age in relation to A1C (P = 0.0266), but no significant interaction of vitamin D status with diabetes status or BMI (regardless of diabetes status).

We observed an inverse association between vitamin D status and A1C level in this sample of U.S. adults 35–74 years of age and among all subjects who did not report history of diabetes. Plausible biological mechanisms may involve insulin secretion and sensitivity (²,⁹,¹⁰). We did not observe this relationship in subjects 18–34 years of age in which the low prevalence of an abnormal A1C (1.5%) could have made an association difficult to detect statistically. Alternatively, this may reflect an age threshold for the effect of vitamin D status on glucose homeostasis. The apparent absence of an association in subjects who reported a history of diabetes or were 75 years of age or older could have been due to their smaller sample sizes and/or confounding by treatment status.

A major strength of our study is the analysis of a large representative sample of the U.S. adult population. We also adjusted for PTH, which may affect insulin sensitivity (¹¹). However, our study has important limitations. The cross-sectional design makes it difficult to establish temporality between vitamin D status and A1C levels, and the analysis derives from only a single measurement of A1C and vitamin D levels. Also, we could not account for diabetes treatment nor medication compliance in the analysis.

Our findings are consistent with similar studies in smaller sized, non-U.S. populations. In one New Zealand study of 250 overweight and obese adults age >18 years, investigators observed a weak, inverse relation between A1C and vitamin D3 levels (¹²). A study of 7,198 British Caucasians showed a nonlinear inverse relationship between vitamin D and A1C (¹³). Our findings also cohere with investigations relating vitamin D status to diabetes from the Third NHANES (¹⁰) and the Medical Research Council Ely Prospective Study 1990–2000 (¹⁴).

In conclusion, this analysis supports an inverse association between vitamin D status and A1C levels in the U.S. adult population 35–74 years of age, which is nearly two-thirds of all U.S. adults (¹⁵), and subjects who do not report a history of diabetes. This suggests a mechanistic link among serum vitamin D concentrations, glucose homeostasis, and the evolution of diabetes in a large segment of U.S. adults at the population level. These findings also highlight the need to consider screening for vitamin D insufficiency in individuals with an elevated A1C level and vice versa. This is important in populations at high risk for both conditions, such as the obese and racial/ethnic minorities. Whether vitamin D supplementation can delay the onset of diabetes remains to be established. Therefore, future studies to clarify the efficacy of vitamin D supplementation in preventing diabetes and pre-diabetes are warranted, especially in populations at high risk.

The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

V.L.F. was supported by in part by National Institutes of Health (NIH) Grant 5R01CA129140. B.S.G. was supported in part by NIH Grant 1R21DK078352.

No potential conflicts of interest relevant to this article were reported.