Accumulating research suggests that circulating concentrations of vitamin D may be inversely related to the prevalence of diabetes (1,2,3,4), to the concentration of glucose (4,5,6,7,8), and to insulin resistance (4,5,8,9). In addition, vitamin D deficiency may be a risk factor for the metabolic syndrome (8,10), a highly prevalent condition among U.S. adults (11). Much remains to be learned, however, about the relationship between vitamin D status and metabolic syndrome. Because this topic has received scant attention and the available information was derived from a small clinically based sample, we sought to examine the nature and strength of the association between serum concentrations of vitamin D and the metabolic syndrome in a large nationally representative sample of the U.S. population.

Between 1988 and 1994, a representative sample of the noninstitutionalized civilian U.S. population, selected using a multistage stratified sampling design, participated in the NHANES III (Third National Health and Nutrition Examination Survey). Survey participants were interviewed and invited for a clinical examination (12,13,14).

The metabolic syndrome was defined according to National Cholesterol Education Program criteria (11,15). Serum concentrations of vitamin D {25-hydroxyvitamin D [25(OH)D]} were measured using a radioimmunoassay method (DiaSorin, Stillwater, MN) (16). Detailed information about procedures for this assay was published in the NHANES III laboratory manual (14).

The analyses included the following variables: age, sex, race or ethnicity (white, African American, Mexican American, and other), education, smoking status (current, former, and never), serum cotinine concentration, concentration of C-reactive protein, total cholesterol concentration, leisure time physical activity, vitamin or mineral use during the previous 24 h (yes/no), alcohol use (times per month), intake of fruits and vegetables (times per day), and season of study participation.

We limited our analyses to 8,421 men and nonpregnant women who were ≥20 years and had fasted ≥8 h. Based on the final analytic sample, we created quintiles of concentration of 25(OH)D from its distribution determined using the sampling weights. To compare proportions across quintiles of serum concentrations of 25(OH)D, we used a test for linear trend. In addition, the associations between the metabolic syndrome and its components and concentrations of 25(OH)D were examined by multiple logistic regression analysis. To account for the complex survey design, we used SUDAAN and the medical examination clinic sampling weights to produce our weighted estimates and standard errors (17).

Among the 8,421 participants, the unadjusted prevalence of the metabolic syndrome was 21.9%. Concentrations of 25(OH)D ranged from 8.7 to 227.9 nmol/l. The mean, median, and geometric mean concentrations were 74.0, 71.0, and 68.1 nmol/l, respectively. The mean concentration of 25(OH)D was 67.1 nmol/l (median 64.1 [range 12.5–192.2]) among those with the metabolic syndrome and 75.9 nmol/l (73.1 [8.7–227.9]) among those without the metabolic syndrome (P < 0.001).

After multiple adjustment, the odds of having the metabolic syndrome decreased progressively across increasing quintiles of concentration of 25(OH)D (Table 1). The associations between 25(OH)D and the metabolic syndrome did not differ between men and women (P = 0.726) or among the three major racial or ethnic groups (P = 0.377). After splitting the lowest quintile into two categories, <25.0 nmol/l (presumed hypovitaminosis D as the new reference category) and 25.0–48.4 nmol/l, while leaving the other quintiles unchanged, the odds ratios for increasing categories of concentration of 25(OH)D were 0.81 (95% CI 0.48–1.39), 0.67 (0.37–1.23), 0.62 (0.33–1.15), 0.50 (0.26–0.93), and 0.38 (0.20–0.72). After excluding people with diagnosed diabetes (n = 7,904), the adjusted odds ratios for having the metabolic syndrome relative to the 1st quintile for the 2nd through 5th quintiles of concentration of 25(OH)D were 0.85 (95% confidence limits 0.61, 1.17), 0.75 (0.54, 1.03), 0.62 (0.46, 0.86), and 0.46 (0.32, 0.66) (P < 0.001 by Wald χ2). Among the components, significant inverse associations were present for quintiles of concentration of 25(OH)D and abdominal adiposity, hypertriglyceridemia, and hyperglycemia.

Studies showing an inverse association between concentrations of vitamin D and insulin resistance provide a possible explanation for our findings of an inverse association between serum concentrations of vitamin D and the prevalence of the metabolic syndrome (4,5,8,9). Insulin resistance is considered a likely mechanism underlying the metabolic syndrome (18). An inverse association between various anthropometric measures and intake of vitamin D or circulating concentrations of vitamin D has been reported by a number of studies (19,20). Because excess weight is a major component of the metabolic syndrome, the associations noted in our analyses may largely reflect an association between concentrations of vitamin D and excess weight.

The principal limitation of our study was its cross-sectional design, and thus the causative nature of the association cannot be established. In addition, this study was based on a single measurement of vitamin D. Finally, parathyroid hormone was not measured in this survey.

Further investigation into whether vitamin D may play a role in the prevention of diabetes and pre-diabetic states appears warranted. Because of the close interrelationships between vitamin D, parathyroid hormone, calcium, and phosphate, untangling the contributions of each of these factors on insulin resistance and glucose homeostasis is important in developing possible future approaches to the prevention of insulin resistance, the metabolic syndrome, and diabetes.

Table 1—

Unadjusted prevalence and adjusted odds ratios and 95% confidence limits of having the metabolic syndrome by quintiles of serum vitamin D concentration among 8,421 U.S. adults aged ≥20 years, NHANES III, 1988–1994

Quintiles of vitamin D (nmol/l)
1 (≤48.4)2 (48.5–63.4)3 (63.5–78.1)4 (78.2–96.3)5 (≥96.4)P*
Metabolic syndrome       
    Unadjusted prevalence† 27.5 (1.7) 26.6 (1.4) 23.3 (1.5) 18.7 (1.3) 13.5 (1.7) <0.001 
    Model 1‡ 1.00 0.91 (0.72, 1.17) 0.80 (0.62, 1.03) 0.65 (0.51, 0.83) 0.49 (0.37, 0.66) <0.001 
    Model 2§ 1.00 0.82 (0.60, 1.10) 0.75 (0.55, 1.02) 0.60 (0.44, 0.83) 0.46 (0.32, 0.67) <0.001 
Components of the metabolic syndrome       
    Abdominal obesity       
Unadjusted prevalence† 49.9 (1.9) 43.7 (1.9) 37.2 (1.5) 31.0 (1.5) 19.3 (1.5) <0.001 
Model 1‡ 1.00 0.74 (0.60, 0.91) 0.58 (0.49, 0.70) 0.47 (0.37, 0.59) 0.27 (0.21, 0.33) <0.001 
Model 2§ 1.00 0.78 (0.61, 0.98) 0.65 (0.52, 0.81) 0.55 (0.41, 0.72) 0.30 (0.21, 0.42) <0.001 
Model 3‖ 1.00 0.79 (0.63, 0.98) 0.68 (0.55, 0.85) 0.58 (0.44, 0.76) 0.32 (0.23, 0.45) <0.001 
    Hypertriglyceridemia       
Unadjusted prevalence† 29.3 (1.5) 32.8 (1.4) 32.0 (2.0) 24.4 (1.8) 24.2 (2.6) <0.001 
Model 1‡ 1.00 1.16 (0.96, 1.41) 1.17 (0.93, 1.47) 0.83 (0.66, 1.06) 0.90 (0.70, 1.14) 0.016 
Model 2§ 1.00 0.89 (0.69, 1.15) 0.88 (0.67, 1.16) 0.58 (0.45, 0.75) 0.59 (0.44, 0.80) <0.001 
Model 3‖ 1.00 0.98 (0.75, 1.27) 1.03 (0.78, 1.37) 0.66 (0.50, 0.86) 0.76 (0.57, 1.01) 0.002 
Model 4 1.00 1.00 (0.80, 1.24) 1.02 (0.80, 1.31) 0.67 (0.52, 0.85) 0.84 (0.64, 1.10) 0.005 
    Low HDL cholesterol       
Unadjusted prevalence† 39.8 (1.9) 37.9 (1.8) 38.4 (2.3) 36.6 (2.1) 33.3 (2.3) 0.031 
Model 1‡ 1.00 0.92 (0.75, 1.12) 0.94 (0.73, 1.22) 0.88 (0.69, 1.10) 0.77 (0.60, 0.97) 0.172 
Model 2§ 1.00 0.84 (0.69, 1.04) 0.89 (0.69, 1.16) 0.81 (0.64, 1.03) 0.71 (0.56, 0.90) 0.050 
Model 3‖ 1.00 0.88 (0.71, 1.09) 0.99 (0.76, 1.29) 1.03 (0.80, 1.31) 0.96 (0.76, 1.22) 0.636 
Model 4 1.00 0.88 (0.71, 1.08) 0.99 (0.76, 1.29) 1.03 (0.82, 1.30) 0.92 (0.72, 1.17) 0.567 
    High blood pressure       
Unadjusted prevalence† 34.4 (1.5) 36.5 (1.7) 30.7 (2.1) 29.5 (1.8) 23.9 (1.9) <0.001 
Model 1‡ 1.00 1.06 (0.89, 1.26) 0.84 (0.67, 1.05) 0.91 (0.69, 1.20) 0.79 (0.61, 1.02) 0.067 
Model 2§ 1.00 1.10 (0.89, 1.37) 0.91 (0.71, 1.18) 1.00 (0.73, 1.37) 0.88 (0.63, 1.21) 0.416 
Model 3‖ 1.00 1.17 (0.95, 1.44) 1.00 (0.77, 1.30) 1.16 (0.85, 1.59) 1.07 (0.77, 1.50) 0.489 
    Hyperglycemia       
Unadjusted prevalence† 14.6 (1.0) 15.1 (1.2) 9.9 (1.2) 10.8 (1.1) 6.3 (1.0) <0.001 
Model 1‡ 1.00 1.01 (0.78, 1.31) 0.63 (0.44, 0.90) 0.78 (0.58, 1.05) 0.50 (0.34, 0.73) <0.001 
Model 2§ 1.00 0.92 (0.69, 1.23) 0.59 (0.40, 0.87) 0.71 (0.50, 1.01) 0.44 (0.29, 0.68) <0.001 
Model 3‖ 1.00 0.98 (0.74, 1.29) 0.61 (0.42, 0.89) 0.83 (0.59, 1.18) 0.54 (0.35, 0.84) 0.005 
Quintiles of vitamin D (nmol/l)
1 (≤48.4)2 (48.5–63.4)3 (63.5–78.1)4 (78.2–96.3)5 (≥96.4)P*
Metabolic syndrome       
    Unadjusted prevalence† 27.5 (1.7) 26.6 (1.4) 23.3 (1.5) 18.7 (1.3) 13.5 (1.7) <0.001 
    Model 1‡ 1.00 0.91 (0.72, 1.17) 0.80 (0.62, 1.03) 0.65 (0.51, 0.83) 0.49 (0.37, 0.66) <0.001 
    Model 2§ 1.00 0.82 (0.60, 1.10) 0.75 (0.55, 1.02) 0.60 (0.44, 0.83) 0.46 (0.32, 0.67) <0.001 
Components of the metabolic syndrome       
    Abdominal obesity       
Unadjusted prevalence† 49.9 (1.9) 43.7 (1.9) 37.2 (1.5) 31.0 (1.5) 19.3 (1.5) <0.001 
Model 1‡ 1.00 0.74 (0.60, 0.91) 0.58 (0.49, 0.70) 0.47 (0.37, 0.59) 0.27 (0.21, 0.33) <0.001 
Model 2§ 1.00 0.78 (0.61, 0.98) 0.65 (0.52, 0.81) 0.55 (0.41, 0.72) 0.30 (0.21, 0.42) <0.001 
Model 3‖ 1.00 0.79 (0.63, 0.98) 0.68 (0.55, 0.85) 0.58 (0.44, 0.76) 0.32 (0.23, 0.45) <0.001 
    Hypertriglyceridemia       
Unadjusted prevalence† 29.3 (1.5) 32.8 (1.4) 32.0 (2.0) 24.4 (1.8) 24.2 (2.6) <0.001 
Model 1‡ 1.00 1.16 (0.96, 1.41) 1.17 (0.93, 1.47) 0.83 (0.66, 1.06) 0.90 (0.70, 1.14) 0.016 
Model 2§ 1.00 0.89 (0.69, 1.15) 0.88 (0.67, 1.16) 0.58 (0.45, 0.75) 0.59 (0.44, 0.80) <0.001 
Model 3‖ 1.00 0.98 (0.75, 1.27) 1.03 (0.78, 1.37) 0.66 (0.50, 0.86) 0.76 (0.57, 1.01) 0.002 
Model 4 1.00 1.00 (0.80, 1.24) 1.02 (0.80, 1.31) 0.67 (0.52, 0.85) 0.84 (0.64, 1.10) 0.005 
    Low HDL cholesterol       
Unadjusted prevalence† 39.8 (1.9) 37.9 (1.8) 38.4 (2.3) 36.6 (2.1) 33.3 (2.3) 0.031 
Model 1‡ 1.00 0.92 (0.75, 1.12) 0.94 (0.73, 1.22) 0.88 (0.69, 1.10) 0.77 (0.60, 0.97) 0.172 
Model 2§ 1.00 0.84 (0.69, 1.04) 0.89 (0.69, 1.16) 0.81 (0.64, 1.03) 0.71 (0.56, 0.90) 0.050 
Model 3‖ 1.00 0.88 (0.71, 1.09) 0.99 (0.76, 1.29) 1.03 (0.80, 1.31) 0.96 (0.76, 1.22) 0.636 
Model 4 1.00 0.88 (0.71, 1.08) 0.99 (0.76, 1.29) 1.03 (0.82, 1.30) 0.92 (0.72, 1.17) 0.567 
    High blood pressure       
Unadjusted prevalence† 34.4 (1.5) 36.5 (1.7) 30.7 (2.1) 29.5 (1.8) 23.9 (1.9) <0.001 
Model 1‡ 1.00 1.06 (0.89, 1.26) 0.84 (0.67, 1.05) 0.91 (0.69, 1.20) 0.79 (0.61, 1.02) 0.067 
Model 2§ 1.00 1.10 (0.89, 1.37) 0.91 (0.71, 1.18) 1.00 (0.73, 1.37) 0.88 (0.63, 1.21) 0.416 
Model 3‖ 1.00 1.17 (0.95, 1.44) 1.00 (0.77, 1.30) 1.16 (0.85, 1.59) 1.07 (0.77, 1.50) 0.489 
    Hyperglycemia       
Unadjusted prevalence† 14.6 (1.0) 15.1 (1.2) 9.9 (1.2) 10.8 (1.1) 6.3 (1.0) <0.001 
Model 1‡ 1.00 1.01 (0.78, 1.31) 0.63 (0.44, 0.90) 0.78 (0.58, 1.05) 0.50 (0.34, 0.73) <0.001 
Model 2§ 1.00 0.92 (0.69, 1.23) 0.59 (0.40, 0.87) 0.71 (0.50, 1.01) 0.44 (0.29, 0.68) <0.001 
Model 3‖ 1.00 0.98 (0.74, 1.29) 0.61 (0.42, 0.89) 0.83 (0.59, 1.18) 0.54 (0.35, 0.84) 0.005 
*

For prevalence, P value is for a test for linear trend; for odds ratio, P value is for the Wald χ2 test.

†

Data represent % (SE).

‡

Model 1: adjusted for age.

§

Model 2: adjusted for age, sex, race or ethnicity, education, smoking status, cotinine concentration, total cholesterol concentration, C-reactive protein concentration, alcohol use, physical activity, intake of fruits and vegetables, vitamin or supplement use, and season of study participation.

‖

Model 3: adjusted for all variables in model 2 plus other components of the metabolic syndrome.

Model 4: adjusted for all variables in model 3 minus concentration of total cholesterol.

View Large
1.
Pietschmann P, Schernthaner G, Woloszczuk W: Serum osteocalcin levels in diabetes mellitus: analysis of the type of diabetes and microvascular complications.
Diabetologia
 
31
:
892
–895,
1988
2.
Scragg R, Holdaway I, Singh V, Metcalf P, Baker J, Dryson E: Serum 25-hydroxyvitamin D3 levels decreased in impaired glucose tolerance and diabetes mellitus.
Diabetes Res Clin Pract
 
27
:
181
–188,
1995
3.
Isaia G, Giorgino R, Adami S: High prevalence of hypovitaminosis D in female type 2 diabetic population (Letter).
Diabetes Care
 
24
:
1496
,
2001
4.
Scragg R, Sowers M, Bell C: Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey.
Diabetes Care
 
27
:
2813
–2818,
2004
5.
Boucher BJ, Mannan N, Noonan K, Hales CN, Evans SJ: Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians.
Diabetologia
 
38
:
1239
–1245,
1995
6.
Baynes KC, Boucher BJ, Feskens EJ, Kromhout D: Vitamin D, glucose tolerance and insulinaemia in elderly men.
Diabetologia
 
40
:
344
–347,
1997
7.
Ortlepp JR, Metrikat J, Albrecht M, von Korff A, Hanrath P, Hoffmann R: The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young men.
Diabet Med
 
20
:
451
–454,
2003
8.
Chiu KC, Chu A, Go VL, Saad MF: Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction.
Am J Clin Nutr
 
79
:
820
–825,
2004
9.
Lind L, Hanni A, Lithell H, Hvarfner A, Sorensen OH, Ljunghall S: Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men.
Am J Hypertens
 
8
:
894
–901,
1995
10.
Boucher BJ: Inadequate vitamin D status: does it contribute to the disorders comprising syndrome ‘X’?
Br J Nutr
 
79
:
315
–327,
1998
11.
Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey.
JAMA
 
287
:
356
–359,
2002
12.
Plan and operation of the Third National Health and Nutrition Examination Survey, 1988–
1994
. Series 1: programs and collection procedures.
Vital Health Stat
 1 Jul 
y
:
1
–407,
1994
13.
Centers for Disease Control and Prevention:
The Third National Health and Nutrition Examination Survey (NHANES III 1988–94) Reference Manuals and Reports
. Bethesda, MD, National Center for Health Statistics, 1996 (CD-ROM)
14.
Gunter EW, Lewis BL, Koncikowski SM:
Laboratory Methods Used for the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994
. Hyattsville, MD, Centers for Disease Control and Prevention, 1996 (included in CD-ROM 6-0178, NHANES III Reference Manuals and Reports)
15.
National Institutes of Health:
Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Executive Summary
. Bethesda, MD, National Institutes of Health, 2001 (NIH publ. no. 01-3670)
16.
Looker AC, Dawson-Hughes B, Calvo MS, Gunter EW, Sahyoun NR: Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III.
Bone
 
30
:
771
–777,
2002
17.
Research Triangle Institute:
SUDAAN User’s Manual, Release 8.0
. Research Triangle Park, NC, Research Triangle Institute, 2002
18.
Reaven GM: Banting Lecture 1988: Role of insulin resistance in human disease.
Diabetes
 
37
:
1595
–1607,
1988
19.
Kamycheva E, Joakimsen RM, Jorde R: Intakes of calcium and vitamin D predict body mass index in the population of Northern Norway.
J Nutr
 
133
:
102
–106,
2003
20.
Parikh SJ, Edelman M, Uwaifo GI, Freedman RJ, Semega-Janneh M, Reynolds J, Yanovski JA: The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults.
J Clin Endocrinol Metab
 
89
:
1196
–1199,
2004

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

DIABETES CARE
2005