High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D

Mayer B Davidson, Petra Duran, Martin L Lee, Theodore C Friedman, Mayer B Davidson, Petra Duran, Martin L Lee, Theodore C Friedman

Abstract

Objective: Low vitamin D levels predict the development of diabetes. This double-blind, randomized, control study in subjects with prediabetes and hypovitaminosis D evaluated whether high doses of vitamin D for 1 year affected insulin secretion, insulin sensitivity, and the development of diabetes.

Research design and methods: A total of 1,551 subjects ≥40 years of age not known to have diabetes were screened with A1C levels. Subjects with A1C levels of 5.8-6.9% underwent an oral glucose tolerance test (OGTT). Subjects with prediabetes and 25-OH vitamin D (25-OHD) levels <30 ng/mL were randomized to receive weekly placebo (n = 53) or vitamin D (n = 56) with doses based on body weight and baseline 25-OHD levels. OGTTs were performed 3, 6, 9, and 12 months later. Insulin secretion and sensitivity were measured, and the proportion of subjects developing diabetes was assessed.

Results: 25-OHD levels rapidly rose from 22 to nearly 70 ng/mL after vitamin D supplementation with a mean weekly dose of 88,865 IU. There were no differences between the placebo and vitamin D groups regarding fasting plasma glucose, 2-h glucose, or insulin secretion and sensitivity or in the percent developing diabetes or returning to normal glucose tolerance. No subjects experienced increased serum or urinary calcium levels. At 12 months, A1C levels were significantly slightly less (0.2%) in the vitamin D group.

Conclusions: In individuals with prediabetes and hypovitaminosis D, doses of vitamin D supplementation designed to raise serum 25-OHD levels into the upper-normal range for 1 year had no effect on insulin secretion, insulin sensitivity, or the development of diabetes compared with placebo administration.

Trial registration: ClinicalTrials.gov NCT00876928.

Figures

Figure 1
Figure 1
Flow diagram of the study. appt, appointment; PCP, primary care physician; rehab, rehabilitation.
Figure 2
Figure 2
Serum 25-OHD levels.
Figure 3
Figure 3
Percent of subjects who developed diabetes or reverted to normal. OGTT diagnostic results at 3, 6, 9, and 12 months.

References

    1. Scragg R, Sowers MF, Bell C, Third National Health and Nutrition Examination Survey Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004;27:2813–2818
    1. Cigolini M, Iagulli MP, Miconi V, Galiotto M, Lombardi S, Targher G. Serum 25-hydroxyvitamin D3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care 2006;29:722–724
    1. Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2007;167:1159–1165
    1. Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008;168:1629–1637
    1. Dalgård C, Petersen MS, Weihe P, Grandjean P. Vitamin D status in relation to glucose metabolism and type 2 diabetes in septuagenarians. Diabetes Care 2011;34:1284–1288
    1. Gupta AK, Brashear MM, Johnson WD. Prediabetes and prehypertension in healthy adults are associated with low vitamin D levels. Diabetes Care 2011;34:658–660
    1. Pinelli NR, Jaber LA, Brown MB, Herman WH. Serum 25-hydroxy vitamin D and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care 2010;33:1373–1375
    1. Shankar A, Sabanayagam C, Kalidindi S. Serum 25-hydroxyvitamin D levels and prediabetes among subjects free of diabetes. Diabetes Care 2011;34:1114–1119
    1. Knekt P, Laaksonen M, Mattila C, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology 2008;19:666–671
    1. Pittas AG, Sun Q, Manson JE, Dawson-Hughes B, Hu FB. Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in women. Diabetes Care 2010;33:2021–2023
    1. Gagnon C, Lu ZX, Magliano DJ, et al. Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study). Diabetes Care 2011;34:1133–1138
    1. Pittas AG, Nelson J, Mitri J, et al. Diabetes Prevention Program Research Group Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program. Diabetes Care 2012;35:565–573
    1. National Diabetes Data Group. Diabetes in America 2nd ed. National Institutes of Health, Bethesda, MD, 1995 (NIH publ. no.)
    1. Chang A, Frank J, Knaebel J, Fullam J, Pardo S, Simmons DA. Evaluation of an over-the-counter glycated hemoglobin (A1C) test kit. J Diabetes Sci Tech 2010;4:1495–1503
    1. Buell C, Kermah D, Davidson MB. Utility of A1C for diabetes screening in the 1999–2004 NHANES population. Diabetes Care 2007;30:2233–2235
    1. American Diabetes Association Standards of medical care in diabetes—2012. Diabetes Care 2012;35(Suppl 1.):S11–S63
    1. World Health Organization Definitions, Diagnosis, and Classification of Diabetes Mellitus and its Complication: Report of a WHO consultation. Part 1. Diagnosis and Classification of Diabetes Mellitus. Geneva, World Health Org., 1999
    1. Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int 1998;8:222–230
    1. de Boer IH, Tinker LF, Connelly S, et al. Women’s Health Initiative Investigators Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women’s Health Initiative. Diabetes Care 2008;31:701–707
    1. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–419
    1. Stumvoll M, Mitrakou A, Pimenta W, et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2000;23:295–301
    1. Jensen CC, Cnop M, Hull RL, Fujimoto WY, Kahn SE; American Diabetes Association GENNID Study Group. B-Cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the U.S. Diabetes 2002;51:2170–2178
    1. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462–1470
    1. Retnakaran R, Shen S, Hanley AJ, Vuksan V, Hamilton JK, Zinman B. Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity (Silver Spring) 2008;16:1901–1907
    1. Utzschneider KM, Prigeon RL, Faulenbach MV, et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care 2009;32:335–341
    1. Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 2007;30:980–986
    1. Parekh D, Sarathi V, Shivane VK, Bandgar TR, Menon PS, Shah NS. Pilot study to evaluate the effect of short-term improvement in vitamin D status on glucose tolerance in patients with type 2 diabetes mellitus. Endocr Pract 2010;16:600–608
    1. Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur J Nutr 2009;48:349–354
    1. Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403
    1. Knowler WC, Hamman RF, Edelstein SL, et al. Diabetes Prevention Program Research Group Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. Diabetes 2005;54:1150–1156
    1. Mooy JM, Grootenhuis PA, de Vries H, et al. Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study. Diabetologia 1996;39:298–305
    1. Ko GTC, Chan JCN, Woo J, et al. The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors. Ann Clin Biochem 1998;35:62–67
    1. Brohall G, Behre CJ, Hulthe J, Wikstrand J, Fagerberg B. Prevalence of diabetes and impaired glucose tolerance in 64-year-old Swedish women: experiences of using repeated oral glucose tolerance tests. Diabetes Care 2006;29:363–367
    1. Friedman TC. Vitamin D supplementation to prevent the progression of prediabetes to diabetes: getting closer to a recommendation. Transl Res 2011;158:273–275

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