Vitamin D functions are not limited to skeletal health benefits and may extend to preservation of insulin secretion and insulin sensitivity. This review summarizes the literature related to potential vitamin D influences on glucose homeostasis and insulin sensitivity. Cross-sectional data provide some evidence that circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with insulin resistance, although direct measurements of insulin sensitivity are required for confirmation. Reported associations with insulin secretion, however, are contradictory. Available prospective studies support a protective influence of high 25(OH)D concentrations on type 2 diabetes mellitus risk. There is a general lack of consistency in vitamin D intervention outcomes on insulin secretion and sensitivity, likely due to differences in subject populations, length of interventions, and forms of vitamin D supplementation. Vitamin D receptor gene polymorphisms and vitamin D interactions with the insulin like growth factor system may further influence glucose homeostasis. The ambiguity of optimal vitamin D dosing regimens and optimal therapeutic concentrations of serum 25(OH)D limit available intervention studies. Future studies, including cross-sectional and prospective, should be performed in populations at high risk for both vitamin D deficiency and type 2 diabetes mellitus. Well-designed, placebo-controlled, randomized intervention studies are required to establish a true protective influence of vitamin D on glucose homeostasis.

Vitamin D deficiency may increase the risk for metabolic syndrome. We determined the relationship of serum 25-hydroxyvitamin D (25(OH)D) with metabolic syndrome components in obese adolescent females and assessed whether vitamin D treatment corrects metabolic disturbances. Eighty postmenarchal adolescents (53 African American (AA) and 27 Caucasian American (CA)) were evaluated with blood pressures and fasting measurements of serum 25(OH)D, lipid profile, C-reactive protein, alanine transaminases (ALTs) and aspartate transaminases followed by an oral glucose tolerance test. A subgroup (n = 14) of vitamin D deficient subjects were re-evaluated following vitamin D treatment. Among all subjects, 25(OH)D was inversely associated with fasting glucose (r = −0.28, P = 0.02) and positively associated with low-density lipoprotein (LDL) cholesterol (r = 0.31, P = 0.008), independent of race and BMI. In analyses by race, adjusted for BMI, 25(OH)D was inversely associated with fasting insulin in CA (r = −0.42, P = 0.03) but not AA (r = 0.11, P = 0.43) whereas 25(OH)D was positively associated with ALT in AA, but not CA (r = 0.29, P = 0.04 vs. r = −0.21, P = 0.32). Fasting glucose improved in vitamin D treated subgroup (from 89.07 ± 8.3 mg/dl to 84.34 ± 8.4 mg/dl, P = 0.05). A trend toward improvement in fasting glucose remained after exclusion of four subjects whose serum 25(OH)D2 did not improve following treatment (P = 0.12). In conclusion, serum 25(OH)D was inversely associated with fasting glucose, and vitamin D treatment had beneficial effects on fasting glucose. Relationships of 25(OH)D with fasting insulin and ALT were ethnic specific. The positive relationship with LDL and ALT were suggestive of possible adverse influences of vitamin D.

Vitamin D deficiency is highly prevalent in obese, AA female adolescents and may promote insulin resistance. Our data suggest that a 25(OH)D concentration of 15 ng/ml or less may be the threshold by which vitamin D deficiency confers negative effects on insulin sensitivity.