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In recent years, the relationships between vitamin D and factors involved in glucose homeostasis have received a great deal of attention. Few studies have been conducted using pediatric samples (1–3). Because the prevalence of deficient or insufficient vitamin D status is high among children and adolescents in the U.S. and is possibly increasing (4,5), any deleterious effect of suboptimal vitamin D status on glucose homeostasis is of interest, especially in light of concerns about increases in diabetes among youth in the U.S. (6). Most previous studies have used small, selected samples of adolescents. To provide additional insights into the associations between circulating concentrations of vitamin D and concentrations of insulin and glucose, we examined data from a large, representative sample of adolescents that included African Americans and Mexican Americans in the U.S.

ed small, selected samples of adolescents. To provide additional insights into the associations between circulating concentrations of vitamin D and concentrations of insulin and glucose, we examined data from a large, representative sample of adolescents that included African Americans and Mexican Americans in the U.S. RESEARCH DESIGN AND METHODS We used data from the National Health and Nutrition Examination Survey (NHANES) 2001–2006 (7). The participants were recruited using a multistage, stratified sampling design, which is an efficient approach to obtaining a sample representative of the civilian noninstitutionalized population. The participants were interviewed at home and were invited to attend a mobile examination center, where they were asked to complete additional questionnaires, to undergo various examinations, and to provide a blood sample. The study received approval from the NHANES Institutional Review Board, and participants were asked to sign an informed consent form. Details about the survey can be found elsewhere (7).

center, where they were asked to complete additional questionnaires, to undergo various examinations, and to provide a blood sample. The study received approval from the NHANES Institutional Review Board, and participants were asked to sign an informed consent form. Details about the survey can be found elsewhere (7). Serum concentrations of vitamin D (25-hydroxyvitamin D) were measured using the Diasorin 25-OH-vitamin D assay (Diasorin, Stillwater, MN), a radioimmunoassay (8). We created three categories of vitamin D concentrations: deficiency, <50 nmol/L; insufficiency, 50 to <75 nmol/L; and sufficiency, ≥75 nmol/L (9). The methods used to measure insulin (a Pharmacia insulin radioimmunoassay kit, a Tosoh AIA-PACK IRI, and a Merocodia insulin enzyme-linked immunosorbent assay), glucose (a Cobas Mira chemistry system and a Roche/Hitachi 911 analyzer), and HbA1c (Primus automated high-performance liquid chromatography models CLC330 and CLC385 and an HbA1c 2.2 Plus glycohemoglobin analyzer) are described elsewhere (7). Covariates included age, sex, race, or ethnicity (white, African American, Mexican American, other Hispanic, or mixed race), leisure-time physical activity, BMI percentiles, supplement use during the past months (yes or no), concentrations of HDL cholesterol and non-HDL cholesterol, and a 6-month sampling period. To estimate physical activity, we calculated an average daily metabolic equivalent task hours index. BMI percentiles were calculated from measured weight and height using the Centers for Disease Control and Prevention’s growth charts.

entrations of HDL cholesterol and non-HDL cholesterol, and a 6-month sampling period. To estimate physical activity, we calculated an average daily metabolic equivalent task hours index. BMI percentiles were calculated from measured weight and height using the Centers for Disease Control and Prevention’s growth charts. We limited our analyses to participants aged 12–17 years who attended the morning examination and who had fasted at least 8 h. We excluded participants who had been diagnosed with diabetes. Adjusted mean concentrations of insulin (after log transformation), glucose, and HbA1c were calculated using ANCOVA. The statistical significance of the tests for linear trend of means conducted by using general linear contrasts was assessed with an adjusted Wald F statistic that adjusts for the denominator degrees of freedom. The statistical software SUDAAN was used for the analyses to account for the multistage, stratified sampling design. RESULTS During the 6-year study period, 2,070 adolescents, aged 12–17 years, attended the morning examination of the mobile examination center. Data for concentrations of glucose, insulin, and vitamin D were available for 2,028 subjects. After excluding records with missing data for covariates, the final analytic sample comprised 1,941 participants, including 531 whites, 620 African Americans, 632 Mexican Americans, and 158 participants of another race or ethnicity.

or concentrations of glucose, insulin, and vitamin D were available for 2,028 subjects. After excluding records with missing data for covariates, the final analytic sample comprised 1,941 participants, including 531 whites, 620 African Americans, 632 Mexican Americans, and 158 participants of another race or ethnicity. The means were 65.9 pmol/L (geometric mean: 50.3 pmol/L), 5.1 mmol/L, 5.2%, and 59 nmol/L for concentrations of insulin, glucose, HbA1c, and vitamin D, respectively. Furthermore, 31.5 ± 2.1% (means ± SE; male subjects 27.4%, female subjects 35.7%) had a concentration of vitamin D <50 nmol/L, 48.3 ± 2.0% (male subjects 49.8%, female subjects 46.6%) had a concentration 50 to <75 nmol/L, and 20.3 ± 1.6% (male subjects 22.7%, female subjects 17.7%) had a concentration ≥75 nmol/L. Adjusted concentrations of insulin were approximately 24% lower among male subjects with a concentration of vitamin D ≥75 nmol/L than among male subjects with a concentration of vitamin D <50 nmol/L (P = 0.003) (Table 1). Concentrations of vitamin D were inversely associated with concentrations of glucose among Mexican American male subjects (P = 0.007). No significant associations between concentrations of vitamin D and HbA1c were detected. Table 1 Unadjusted and adjusted geometric means for concentrations of insulin and means for glucose and HbA1c by levels of concentrations of vitamin D among participants aged 12–17 years, NHANES 2001–2006

Adjusted concentrations of insulin were approximately 24% lower among male subjects with a concentration of vitamin D ≥75 nmol/L than among male subjects with a concentration of vitamin D <50 nmol/L (P = 0.003) (Table 1). Concentrations of vitamin D were inversely associated with concentrations of glucose among Mexican American male subjects (P = 0.007). No significant associations between concentrations of vitamin D and HbA1c were detected. Table 1 Unadjusted and adjusted geometric means for concentrations of insulin and means for glucose and HbA1c by levels of concentrations of vitamin D among participants aged 12–17 years, NHANES 2001–2006 n Unadjusted vitamin D (nmol/L) Vitamin D adjusted for sampling period (nmol/L) Vitamin D adjusted for multiple covariates (nmol/L)* <50 50 to <75 ≥75 P† <50 50 to <75 ≥75 P† <50 50 to <75 ≥75 P† Insulin (pmol/L) Total 1,941 60.1 50.4 44.7 <0.001 60.3 50.4 44.5 <0.001 56.3 51.2 47.7 0.004 Male subjects 1,000 60.4 48.2 40.7 <0.001 60.3 48.2 40.7 <0.001 56.7 48.5 43.3 0.003 Female subjects 941 59.8 53.0 50.8 0.040 60.3 52.8 50.2 0.021 55.7 54.4 54.7 0.818 White subjects 531 57.5 51.8 44.7 0.013 57.6 51.8 44.7 0.012 52.8 51.5 47.4 0.172 African American subjects 620 59.7 46.1 43.3 0.053 60.1 45.3 42.8 0.033 57.4 51.7 48.1 0.080 Mexican American subjects 632 68.4 51.3 44.9 <0.001 68.0 51.5 45.4 <0.001 62.8 54.0 52.3 0.008 Male subjects White 268 72.5 50.2 40.7 0.001 71.8 50.1 41.0 0.001 58.8 50.2 44.6 0.043 African American 343 50.2 40.2 37.7 0.075 50.4 39.9 37.3 0.053 48.2 44.5 37.4 0.033 Mexican American 313 67.7 49.2 40.3 <0.001 67.4 49.3 40.6 <0.001 60.9 51.5 46.3 0.005 Female subjects White 263 48.3 53.5 50.5 0.701 48.5 53.6 50.1 0.776 46.9 53.0 52.7 0.236 African American 277 69.3 57.3 78.6 0.773 69.7 55.9 77.1 0.808 68.9 58.6 78.4 0.677 Mexican American 319 69.1 54.2 58.9 0.301 68.5 54.7 60.1 0.349 65.5 57.5 63.3 0.726 Glucose (mmol/L) Total 1,941 5.1 5.1 5.1 0.469 5.1 5.1 5.1 0.806 5.1 5.1 5.1 0.457 Male subjects 1,000 5.2 5.2 5.2 0.847 5.2 5.2 5.2 0.993 5.2 5.2 5.2 0.710 Female subjects 941 4.9 5.0 4.9 0.862 5.0 5.0 4.9 0.503 5.0 5.0 4.9 0.401 White subjects 531 5.1 5.1 5.1 0.812 5.1 5.1 5.1 0.982 5.1 5.1 5.1 0.728 African American subjects 620 5.0 4.9 4.9 0.397 5.0 4.9 4.9 0.321 5.0 4.9 4.8 0.095 Mexican American subjects 632 5.2 5.1 5.1 0.119 5.2 5.1 5.1 0.072 5.2 5.1 5.0 0.012 Male subjects White 268 5.3 5.2 5.2 0.916 5.3 5.2 5.2 0.841 5.2 5.2 5.2 0.973 African American 343 5.1 5.0 4.9 0.072 5.1 5.0 4.9 0.071 5.1 5.0 4.9 0.098 Mexican American 313 5.4 5.2 5.2 0.009 5.4 5.2 5.2 0.003 5.4 5.2 5.2 0.007 Female subjects White 263 4.9 5.0 4.9 0.730 5.0 5.0 4.9 0.591 5.0 5.0 4.9 0.584 African American 277 4.9 4.8 4.8 0.907 4.9 4.8 4.8 0.789 4.9 4.8 4.8 0.706 Mexican American 319 5.1 5.0 4.9 0.150 5.1 5.0 4.9 0.159 5.1 5.0 4.9 0.258 HbA1c (%) Total 1,941 5.2 5.

can 313 5.4 5.2 5.2 0.009 5.4 5.2 5.2 0.003 5.4 5.2 5.2 0.007 Female subjects White 263 4.9 5.0 4.9 0.730 5.0 5.0 4.9 0.591 5.0 5.0 4.9 0.584 African American 277 4.9 4.8 4.8 0.907 4.9 4.8 4.8 0.789 4.9 4.8 4.8 0.706 Mexican American 319 5.1 5.0 4.9 0.150 5.1 5.0 4.9 0.159 5.1 5.0 4.9 0.258 HbA1c (%) Total 1,941 5.2 5. 2 5.2 0.471 5.2 5.2 5.2 0.286 5.2 5.2 5.2 0.626 Male subjects 1,000 5.2 5.2 5.2 0.803 5.2 5.2 5.2 1.000 5.2 5.2 5.2 0.187 Female subjects 941 5.2 5.2 5.1 0.227 5.2 5.1 5.1 0.086 5.2 5.2 5.2 0.694 White subjects 531 5.1 5.2 5.2 0.282 5.1 5.2 5.2 0.364 5.1 5.2 5.2 0.487 African American subjects 620 5.3 5.3 5.2 0.578 5.3 5.3 5.2 0.552 5.3 5.3 5.2 0.427 Mexican American subjects 632 5.2 5.2 5.2 0.562 5.2 5.2 5.2 0.832 5.2 5.2 5.2 0.621 Male subjects White 268 5.1 5.2 5.2 0.287 5.1 5.2 5.2 0.208 5.1 5.2 5.2 0.182 African American 343 5.3 5.3 5.2 0.587 5.3 5.3 5.2 0.575 5.3 5.4 5.2 0.596 Mexican American 313 5.2 5.2 5.2 0.815 5.2 5.2 5.2 0.676 5.2 5.2 5.2 0.600 Female subjects White 263 5.1 5.1 5.1 0.906 5.1 5.2 5.1 0.910 5.1 5.1 5.1 0.899 African American 277 5.3 5.2 5.1 0.493 5.3 5.2 5.1 0.443 5.3 5.2 5.1 0.298 Mexican American 319 5.1 5.2 5.1 0.891 5.1 5.2 5.1 0.905 5.1 5.2 5.2 0.851 *Adjusted for age; sex; race, or ethnicity; leisure-time physical activity; 30-day use of vitamins, minerals, or other dietary supplements; BMI percentile; HDL cholesterol; non-HDL cholesterol; and examination period. Examination period was a dichotomous variable representing the two 6-month periods of 1 November through 30 April and 1 May through 31 October.

2 5.2 0.471 5.2 5.2 5.2 0.286 5.2 5.2 5.2 0.626 Male subjects 1,000 5.2 5.2 5.2 0.803 5.2 5.2 5.2 1.000 5.2 5.2 5.2 0.187 Female subjects 941 5.2 5.2 5.1 0.227 5.2 5.1 5.1 0.086 5.2 5.2 5.2 0.694 White subjects 531 5.1 5.2 5.2 0.282 5.1 5.2 5.2 0.364 5.1 5.2 5.2 0.487 African American subjects 620 5.3 5.3 5.2 0.578 5.3 5.3 5.2 0.552 5.3 5.3 5.2 0.427 Mexican American subjects 632 5.2 5.2 5.2 0.562 5.2 5.2 5.2 0.832 5.2 5.2 5.2 0.621 Male subjects White 268 5.1 5.2 5.2 0.287 5.1 5.2 5.2 0.208 5.1 5.2 5.2 0.182 African American 343 5.3 5.3 5.2 0.587 5.3 5.3 5.2 0.575 5.3 5.4 5.2 0.596 Mexican American 313 5.2 5.2 5.2 0.815 5.2 5.2 5.2 0.676 5.2 5.2 5.2 0.600 Female subjects White 263 5.1 5.1 5.1 0.906 5.1 5.2 5.1 0.910 5.1 5.1 5.1 0.899 African American 277 5.3 5.2 5.1 0.493 5.3 5.2 5.1 0.443 5.3 5.2 5.1 0.298 Mexican American 319 5.1 5.2 5.1 0.891 5.1 5.2 5.1 0.905 5.1 5.2 5.2 0.851 *Adjusted for age; sex; race, or ethnicity; leisure-time physical activity; 30-day use of vitamins, minerals, or other dietary supplements; BMI percentile; HDL cholesterol; non-HDL cholesterol; and examination period. Examination period was a dichotomous variable representing the two 6-month periods of 1 November through 30 April and 1 May through 31 October. †P value for adjusted Wald F test for linear contrast.

2 5.2 0.471 5.2 5.2 5.2 0.286 5.2 5.2 5.2 0.626 Male subjects 1,000 5.2 5.2 5.2 0.803 5.2 5.2 5.2 1.000 5.2 5.2 5.2 0.187 Female subjects 941 5.2 5.2 5.1 0.227 5.2 5.1 5.1 0.086 5.2 5.2 5.2 0.694 White subjects 531 5.1 5.2 5.2 0.282 5.1 5.2 5.2 0.364 5.1 5.2 5.2 0.487 African American subjects 620 5.3 5.3 5.2 0.578 5.3 5.3 5.2 0.552 5.3 5.3 5.2 0.427 Mexican American subjects 632 5.2 5.2 5.2 0.562 5.2 5.2 5.2 0.832 5.2 5.2 5.2 0.621 Male subjects White 268 5.1 5.2 5.2 0.287 5.1 5.2 5.2 0.208 5.1 5.2 5.2 0.182 African American 343 5.3 5.3 5.2 0.587 5.3 5.3 5.2 0.575 5.3 5.4 5.2 0.596 Mexican American 313 5.2 5.2 5.2 0.815 5.2 5.2 5.2 0.676 5.2 5.2 5.2 0.600 Female subjects White 263 5.1 5.1 5.1 0.906 5.1 5.2 5.1 0.910 5.1 5.1 5.1 0.899 African American 277 5.3 5.2 5.1 0.493 5.3 5.2 5.1 0.443 5.3 5.2 5.1 0.298 Mexican American 319 5.1 5.2 5.1 0.891 5.1 5.2 5.1 0.905 5.1 5.2 5.2 0.851 *Adjusted for age; sex; race, or ethnicity; leisure-time physical activity; 30-day use of vitamins, minerals, or other dietary supplements; BMI percentile; HDL cholesterol; non-HDL cholesterol; and examination period. Examination period was a dichotomous variable representing the two 6-month periods of 1 November through 30 April and 1 May through 31 October. †P value for adjusted Wald F test for linear contrast. CONCLUSIONS After adjusting for covariates, we found significant inverse associations between concentrations of vitamin D and insulin among adolescent male subjects but not female subjects. Several previous reports have noted inverse relationships between concentrations of vitamin D and surrogate measures of insulin resistance in samples of obese adolescents (1,2) and in a population-based sample of children and adolescents (3). Studies in animals and humans suggest that vitamin D status affects insulin secretion (10), vitamin D receptor expression (11), and tyrosine phosphorylation of insulin receptor substrate 1 (12).

of insulin resistance in samples of obese adolescents (1,2) and in a population-based sample of children and adolescents (3). Studies in animals and humans suggest that vitamin D status affects insulin secretion (10), vitamin D receptor expression (11), and tyrosine phosphorylation of insulin receptor substrate 1 (12). The large, nationally representative sample of adolescents represents an important strength of our study. Several limitations deserve to be acknowledged. The cross-sectional study design precludes establishing causality. The possible effect of the use of different methods to measure concentrations of insulin, glucose, and HbA1c during the various survey cycles on our results is unclear. Concern has been expressed about possible assay variability for the vitamin D assay in the NHANES (13). However, the apparent impact on vitamin D parameters for the period of 2000–2004 was small (14). We were unable to adjust for Tanner stage because this information was not collected.

cycles on our results is unclear. Concern has been expressed about possible assay variability for the vitamin D assay in the NHANES (13). However, the apparent impact on vitamin D parameters for the period of 2000–2004 was small (14). We were unable to adjust for Tanner stage because this information was not collected. Prospective studies and clinical trials are needed to clarify the relationships between concentrations of vitamin D and factors involved in glucose homeostasis. Studies using gold-standard techniques to assess insulin resistance also would yield valuable insights. The possibility that vitamin D may affect insulin resistance has potential implications for testing vitamin D concentrations in children and adolescents; recommendations regarding the use of vitamin D supplements and sun exposure, especially in populations at risk for insulin resistance; and fortification of foods. The prevalence of vitamin D deficiency and insufficiency is substantial among adolescents in the U.S.; ~2% of adolescents had concentrations of vitamin D <27 nmol/L, 14% had concentrations <50 nmol/L, and 33% had a concentration ≥75 nmol/L during 2001–2004 (4,5). Acknowledgments No potential conflicts of interest relevant to this article were reported. E.S.F. researched data and wrote the manuscript. G.Z. researched data, contributed to the discussion, and reviewed and edited the manuscript. J.T. contributed to the discussion and reviewed and edited the manuscript. C.L. contributed to the discussion and reviewed and edited the manuscript.