Vitamin D and Diabetes

https://doi.org/10.1016/j.ecl.2013.09.010Get rights and content

Section snippets

Key points

  • Observational studies suggest a link between vitamin D and diabetes.

  • The potential effect of vitamin D appears to be more prominent among persons at risk for diabetes.

  • The optimal blood 25-hydroxyvitamin D concentration associated with reduced risk of type 2 diabetes is not clear.

  • The evidence from randomized controlled trials to support the hypothesis that vitamin D supplementation prevents type 2 diabetes is lacking.

Review of vitamin D physiology

Vitamin D exists in 2 forms: cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2). Vitamin D3 is synthesized in the skin on exposure to solar ultraviolet B (UVB) radiation. During exposure to solar UVB radiation, 7-dehydrocholesterol in the skin is converted to previtamin D3, which is immediately converted to vitamin D3 in a heat-dependent nonenzymatic process. Excessive exposure to sunlight degrades previtamin D3 and vitamin D3 into inactive phyto-products (photo-degradation), avoiding

Classification of vitamin D status

Clinicians and researchers use blood concentration of 25OHD as a biomarker to determine vitamin D status. However, there is no consensus on the 25OHD thresholds for vitamin D deficiency or insufficiency. The main guidelines by the Institute of Medicine (IOM) and the Endocrine Society differ on classification of vitamin D status, as shown in Table 1.1, 2 The differences are explained by what populations were targeted by the guidelines and how the evidence was synthesized. The IOM guidelines

Vitamin D intake requirements

The IOM report on dietary reference intakes for calcium and vitamin D recommends 600 international units (IU) per day of vitamin D for individuals 9 to 70 years and 800 international units for those older than 70 years as the recommended dietary allowance (RDA) (Table 2),2 which is defined as the intake that meets the needs of 97.5% of the healthy population. The IOM report also concluded that the tolerable upper intake level (UL), above which the potential for adverse effects may increase with

Biologic plausibility of an association between vitamin D and type 2 diabetes

Type 2 diabetes results from impaired beta cell function, increased insulin resistance, and systemic inflammation, and there is evidence that vitamin D affects these pathways, as described next.

Cross-Sectional Studies

There are many cross-sectional observational studies that have examined the association between vitamin D and type 2 diabetes and most have reported an inverse association between vitamin D status (25OHD concentration) and prevalent diabetes. One of the largest such cohorts is the National Health and Nutrition Examination Survey in United States, which reported an inverse association between 25OHD concentration and prevalence of diabetes in non-Hispanic white and Mexican-American individuals,

The influence of vitamin D supplementation on type 2 diabetes

The effect of vitamin D supplementation on glycemia or incident type 2 diabetes has been reported in several trials with mixed results (Table 4).

In trials that included participants with normal glucose tolerance at baseline, vitamin D supplementation had a neutral effect on measures of glycemia, including fasting plasma glucose or hemoglobin A1c and insulin resistance measured by homeostasis model assessment (HOMA).69, 70, 71, 72, 73, 74, 75, 76, 77 Similarly, vitamin D supplementation had no

Vitamin D and type 1 diabetes

Type 1 diabetes is characterized by autoimmune destruction of pancreatic islet beta cells, leading to absolute insulin deficiency. Many effects of vitamin D on the pathophysiology of type 1 diabetes have been described, including changes in the immune-mediated destruction,89 but also the beta cell itself. The latter effect may, at least in part, be mediated indirectly by the effect of vitamin D on calcium homeostasis. It also has been reported that specific vitamin D receptor polymorphisms

Summary

Findings from basic science suggest that vitamin D may play a significant role in both types of diabetes. In human studies, the evidence for a potential association is stronger for vitamin D and type 2 diabetes with much fewer data on type 1 diabetes. However, the evidence about type 2 diabetes in humans is derived almost exclusively from observational studies, which may be confounded by a variety of factors and, therefore, these studies preclude an assessment of cause and effect. There are no

First page preview

First page preview
Click to open first page preview

References (100)

  • M. Cohen-Lahav et al.

    The anti-inflammatory activity of 1,25-dihydroxyvitamin D3 in macrophages

    J Steroid Biochem Mol Biol

    (2007)
  • E. Liu et al.

    Predicted 25-hydroxyvitamin D score and incident type 2 diabetes in the Framingham Offspring Study

    Am J Clin Nutr

    (2010)
  • J.L. Anderson et al.

    Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population

    Am J Cardiol

    (2010)
  • M.J. Bolland et al.

    Vitamin D insufficiency and health outcomes over 5 y in older women

    Am J Clin Nutr

    (2010)
  • A. Zittermann et al.

    Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers

    Am J Clin Nutr

    (2009)
  • J. Mitri et al.

    Effects of vitamin D and calcium supplementation on pancreatic beta cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial

    Am J Clin Nutr

    (2011)
  • S. Nazarian et al.

    Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose

    Transl Res

    (2011)
  • B. Nikooyeh et al.

    Daily consumption of vitamin D- or vitamin D + calcium-fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial

    Am J Clin Nutr

    (2011)
  • T. Takiishi et al.

    Vitamin D and diabetes

    Rheum Dis Clin North Am

    (2012)
  • E. Hypponen et al.

    Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study

    Lancet

    (2001)
  • M.F. Holick et al.

    Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline

    J Clin Endocrinol Metab

    (2011)
  • Institute of Medicine

    Dietary reference intakes for calcium and vitamin D

    (2011)
  • C.J. Rosen et al.

    IOM committee members respond to endocrine society vitamin D guideline

    J Clin Endocrinol Metab

    (2012)
  • A.W. Norman et al.

    Vitamin D deficiency inhibits pancreatic secretion of insulin

    Science

    (1980)
  • B.S. Chertow et al.

    Cellular mechanisms of insulin release: the effects of vitamin D deficiency and repletion on rat insulin secretion

    Endocrinology

    (1983)
  • S. Kadowaki et al.

    Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas

    J Clin Invest

    (1984)
  • Y. Tanaka et al.

    Effect of vitamin D3 on the pancreatic secretion of insulin and somatostatin

    Acta Endocrinol (Copenh)

    (1984)
  • C. Cade et al.

    Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D–deficient rat in vivo

    Endocrinology

    (1986)
  • P.M. Bourlon et al.

    The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1, 25-dihydroxyvitamin D3 repletion in the islets of langerhans of rats

    J Endocrinol

    (1999)
  • C. Cade et al.

    Rapid normalization/stimulation by 1,25-dihydroxyvitamin D3 of insulin secretion and glucose tolerance in the vitamin D-deficient rat

    Endocrinology

    (1987)
  • S.A. Clark et al.

    Effect of 1,25 dihydroxyvitamin D3 on insulin secretion

    Diabetes

    (1981)
  • J.A. Johnson et al.

    Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28k in human and rat pancreas

    Am J Physiol

    (1994)
  • U. Zeitz et al.

    Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor

    FASEB J

    (2003)
  • I.N. Sergeev et al.

    1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line

    Endocrinology

    (1995)
  • R.D. Milner et al.

    The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro

    Diabetologia

    (1967)
  • K. Yasuda et al.

    Glucose tolerance and insulin secretion in patients with parathyroid disorders. Effect of serum calcium on insulin release

    N Engl J Med

    (1975)
  • O. Gedik et al.

    Effects of hypocalcemia and theophylline on glucose tolerance and insulin release in human beings

    Diabetes

    (1977)
  • T. Fujita et al.

    Insulin secretion after oral calcium load

    Endocrinol Jpn

    (1978)
  • B. Maestro et al.

    Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells

    Endocr J

    (2000)
  • B. Maestro et al.

    Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3)

    Cell Biochem Funct

    (2002)
  • E.O. Ojuka

    Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle

    Proc Nutr Soc

    (2004)
  • D.C. Wright et al.

    Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions

    Diabetes

    (2004)
  • R.L. Byyny et al.

    Cytosolic calcium and insulin resistance in elderly patients with essential hypertension

    Am J Hypertens

    (1992)
  • B. Draznin et al.

    Mechanism of insulin resistance induced by sustained levels of cytosolic free calcium in rat adipocytes

    Endocrinology

    (1989)
  • B. Draznin et al.

    Possible role of cytosolic free calcium concentrations in mediating insulin resistance of obesity and hyperinsulinemia

    J Clin Invest

    (1988)
  • B. Draznin et al.

    Relationship between cytosolic free calcium concentration and 2-deoxyglucose uptake in adipocytes isolated from 2- and 12-month-old rats

    Endocrinology

    (1988)
  • Y. Ohno et al.

    Impaired insulin sensitivity in young, lean normotensive offspring of essential hypertensives: possible role of disturbed calcium metabolism

    J Hypertens

    (1993)
  • S. Segal et al.

    Postprandial changes in cytosolic free calcium and glucose uptake in adipocytes in obesity and non-insulin-dependent diabetes mellitus

    Horm Res

    (1990)
  • M.B. Zemel

    Nutritional and endocrine modulation of intracellular calcium: implications in obesity, insulin resistance and hypertension

    Mol Cell Biochem

    (1998)
  • J.E. Reusch et al.

    Regulation of GLUT-4 phosphorylation by intracellular calcium in adipocytes

    Endocrinology

    (1991)
  • Cited by (184)

    • Vitamin D deficiency and diabetic retinopathy risk

      2023, Journal Francais d'Ophtalmologie
    View all citing articles on Scopus

    Source of Funding: By research grants R01DK76092, U34DK091958 and U01DK098245 (to A.G. Pittas) from the National Institute of Diabetes and Digestive and Kidney Disease, the Office of the Director, National Institutes of Health, and the National Institutes of Health Office of Dietary Supplements.

    View full text