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      Serum 25-Hydroxyvitamin D Levels and Prediabetes Among Subjects Free of Diabetes

      research-article
      , MD, PHD 1 , , MD, PHD 1 , , MS 1 , 2
      Diabetes Care
      American Diabetes Association

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          Abstract

          OBJECTIVE

          Animal studies suggest that low serum 25-hydroxyvitamin D (25[OH]D) may impair insulin synthesis and secretion and be involved in the pathogenesis of diabetes. Results in studies in humans have not been consistent, however. Prediabetes is a stage earlier in the hyperglycemia/diabetes continuum where individuals are at increased risk of developing diabetes and where prevention efforts have been shown to be effective in delaying or preventing the onset of diabetes. However, previous studies have not examined the association between low serum 25(OH)D levels and prediabetes.

          RESEARCH DESIGN AND METHODS

          We examined the 12,719 participants (52.5% women) in the third National Health and Nutrition Examination Survey aged >20 years who were free of diabetes. Serum 25(OH)D levels were categorized into quartiles (≤17.7, 17.8–24.5, 24.6–32.4, >32.4 ng/mL). Prediabetes was defined as a 2-h glucose concentration of 140–199 mg/dL, or a fasting glucose concentration of 110–125 mg/dL, or an A1C value of 5.7–6.4%.

          RESULTS

          Lower serum 25(OH)D levels were associated with prediabetes after adjusting for age, sex, race/ethnicity, season, geographic region, smoking, alcohol intake, BMI, outdoor physical activity, milk consumption, dietary vitamin D, blood pressure, serum cholesterol, C-reactive protein, and glomerular filtration rate. Compared with quartile 4 of 25(OH)D (referent), the odds ratio of prediabetes associated with quartile 1 was 1.47 (95% CI 1.16–1.85; P = 0.001 for trend). Subgroup analyses examining the relation between 25(OH)D and prediabetes by sex, BMI, and hypertension categories also showed a consistent positive association.

          CONCLUSIONS

          Lower serum 25(OH)D levels are associated with prediabetes in a representative sample of U.S. adults.

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          Most cited references15

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          The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.

          Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
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            Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey.

            To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity. We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged > or =20 years with fasting and/or 2-h plasma glucose and serum insulin measurements. Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicity-specific odds ratios (ORs) for diabetes (fasting glucose > or =7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11-0.60] for non-Hispanic whites and 0.17 [0.08-0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD > or =81.0 nmol/l) compared with the lowest 25OHD (< or =43.9 nmol/l). This inverse association was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (log e) was inversely associated with serum 25OHD in Mexican Americans (P=0.0024) and non-Hispanic whites (P=0.058) but not non-Hispanic blacks (P=0.93), adjusting for confounders. These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.
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              The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults.

              We sought to compare the effects of combined calcium and vitamin D supplementation versus placebo on blood glucose and markers of inflammation in nondiabetic adults aged > or =65 years. A total of 314 Caucasian adults without diabetes received either 500 mg calcium citrate and 700 IU vitamin D(3) or placebos daily for 3 years in a double-blind, randomized, controlled trial designed for bone-related outcomes. In a post hoc analysis, fasting plasma glucose (FPG), insulin sensitivity (estimated by homeostasis model assessment of insulin resistance [HOMA-IR]), plasma C-reactive protein, and interleukin-6, were measured at baseline and 3 years. The effects of combined calcium-vitamin D supplementation on 3-year change in FPG depended on baseline FPG (P = 0.02 for interaction). Therefore, we conducted analyses separately in participants with normal fasting glucose (NFG) (FPG <5.6 mmol/l, n = 222) and impaired fasting glucose (IFG) (FPG 5.6-6.9 mmol/l, n = 92) at baseline. Among participants with IFG at baseline, those who took combined calcium-vitamin D supplements had a lower rise in FPG at 3 years compared with those on placebo (0.02 mmol/l [0.4 mg/dl] vs. 0.34 mmol/l [6.1 mg/dl], respectively, P = 0.042) and a lower increase in HOMA-IR (0.05 vs. 0.91, P = 0.031). In the NFG subgroup, there was no difference in the change in FPG or HOMA-IR between the two treatment arms. There were no differences in C-reactive protein or interleukin-6 between the two treatment arms in either subgroup. In healthy, older adults with IFG, supplementation with calcium and vitamin D may attenuate increases in glycemia and insulin resistance that occur over time. However, our findings should be considered hypothesis generating and need to be confirmed in randomized trials specifically designed for the outcomes of interest.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                May 2011
                20 April 2011
                : 34
                : 5
                : 1114-1119
                Affiliations
                [1] 1Department of Community Medicine, West Virginia University School of Medicine, Morgantown, West Virginia
                [2] 2Department of Statistics, West Virginia University, Morgantown, West Virginia
                Author notes
                Corresponding author: Anoop Shankar, ashankar@ 123456hsc.wvu.edu .
                Article
                1203
                10.2337/dc10-1203
                3114501
                21430085
                5ecb7559-4812-4eb8-ab17-53c7d5f27064
                © 2011 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 23 June 2010
                : 17 February 2011
                Categories
                Original Research
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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