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      Baseline Serum 25-Hydroxy Vitamin D Is Predictive of Future Glycemic Status and Insulin Resistance : The Medical Research Council Ely Prospective Study 1990–2000

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          Abstract

          OBJECTIVE—Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks. However, prospective data using the biomarker serum 25-hydroxyvitamin D [25(OH)D] are limited and therefore examined in the present study.

          RESEARCH DESIGN AND METHODS—A total of 524 randomly selected nondiabetic men and women, aged 40–69 years at baseline, with measurements for serum 25(OH)D and IGF-1 in the population-based Ely Study, had glycemic status (oral glucose tolerance), lipids, insulin, anthropometry, and blood pressure measured and metabolic syndrome risk (metabolic syndrome z score) derived at baseline and at 10 years of follow-up.

          RESULTS—Age-adjusted baseline mean serum 25(OH)D was greater in men (64.5 nmol/l [95% CI 61.2–67.9]) than women (57.2 nmol/l [54.4,60.0]) and varied with season (highest late summer). Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia (fasting glucose: β = −0.0023, P = 0.019; 2-h glucose: β = −0.0097, P = 0.006), insulin resistance (fasting insulin β = −0.1467, P = 0.010; homeostasis model assessment of insulin resistance [HOMA-IR]: β = −0.0059, P = 0.005), and metabolic syndrome z score (β = −0.0016, P = 0.048) after adjustment for age, sex, smoking, BMI, season, and baseline value of each metabolic outcome variable. Associations with 2-h glucose, insulin, and HOMA-IR remained significant after further adjustment for IGF-1, parathyroid hormone, calcium, physical activity, and social class.

          CONCLUSIONS—This prospective study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance. These associations are potentially important in understanding the etiology of abnormal glucose metabolism and warrant investigation in larger, specifically designed prospective studies and randomized controlled trials of supplementation.

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          Most cited references45

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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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            Compendium of physical activities: classification of energy costs of human physical activities.

            A coding scheme is presented for classifying physical activity by rate of energy expenditure, i.e., by intensity. Energy cost was established by a review of published and unpublished data. This coding scheme employs five digits that classify activity by purpose (i.e., sports, occupation, self-care), the specific type of activity, and its intensity as the ratio of work metabolic rate to resting metabolic rate (METs). Energy expenditure in kilocalories or kilocalories per kilogram body weight can be estimated for all activities, specific activities, or activity types. General use of this coding system would enhance the comparability of results across studies using self reports of physical activity.
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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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                Author and article information

                Journal
                Diabetes
                diabetes
                Diabetes
                American Diabetes Association
                0012-1797
                1939-327X
                October 2008
                : 57
                : 10
                : 2619-2625
                Affiliations
                [1 ]Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, U.K
                [2 ]Centre for Diabetes and Metabolic Medicine, Bart's and the London School of Medicine and Dentistry, London, U.K
                Author notes

                Corresponding author: Dr. Nita Gandhi Forouhi, nf250@ 123456medschl.cam.ac.uk

                Article
                57102619
                10.2337/db08-0593
                2551670
                18591391
                a566f4d2-f1ea-426e-a8f6-73e63779f142
                Copyright © 2008, 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
                : 1 May 2008
                : 20 June 2008
                Categories
                Signal Transduction

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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