Fun in the Sun: Vitamin D and Diabetes

July 7, 2016

What role, if any, does vitamin D play in the development of diabetes or diabetic complications?

The long, hot days of summer bring fun in the sun and a vitamin D bonanza. But how does that play a role in diabetes? A substantial body of literature has looked at the role of vitamin D in diabetes, but has yet to provide clear answers.

Along with the long-established causal relationship between rickets and hypovitaminosis D, low vitamin D has been linked to a range of other diseases, including hypertension, cancer, cardiovascular disease, and the onset and progression of diabetes.1

Numerous prospective, observational trials have suggested a role for low vitamin D levels in the development of T2DM. A recent observational study of 9841 Danes found that low 25(OH)D levels were linked to significantly higher incidence of T2DM and 22-35% increased risk for T2DM over 29 years.2 And, a meta-analysis of 21 prospective studies found that higher 25(OH)D levels were significantly linked to lower risk of T2DM. Among 76,220 participants with 4996 cases of T2DM in the meta-analysis, each 10 nmol/L increased in 25 (OH)D levels was linked to 4% lower risk of T2DM (P<0.0001).3

As a fat soluble steroid hormone, vitamin D plays multiple physiological roles that may have an impact on insulin secretion, insulin resistance, pancreatic beta cell function, and the development of diabetes.     

The vitamin D receptor is found on pancreatic beta cells, and has been implicated in the progression of T2DM. Animal studies have suggested vitamin D deficiency inhibits insulin secretion. Administering vitamin D restores glucose-mediated insulin secretion and may promote beta cell survival.1 Vitamin D may also stimulate the expression of insulin receptors in various tissues, thereby playing a role in peripheral insulin sensitivity.4

Vitamin D also regulates calbindin, which is found in beta cells and which modulates insulin secretion via regulation of intracellular calcium. Additionally, vitamin D helps regulate parathyroid hormone (PTH), which has been linked to pancreatic insulin synthesis and secretion. Secondary hyperparathyroidism, which may be induced by low vitamin D levels, has been linked to diabetes.1

Finally, vitamin D may have immunomodulatory properties, and has been implicated in several autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and T1DM.1 Vitamin D is thought to have a role in modification of the Th1/Th2 cytokine profile, as well as inhibition of lymphocyte proliferation. Direct modulation of cytokines by vitamin D may decrease the systemic inflammation that plays an important role in the development of T2DM.4 Supporting evidence from human studies, though, is inconsistent regarding the role of vitamin D in systemic inflammation and the development of T2DM.5

Additionally, research has yet to confirm that vitamin D supplementation improves glycemic control or prevents the development of diabetes. The double blind randomized Women’s Health Initiative Calcium/Vitamin D trial included 33,951 postmenopausal women randomized to 1000 mg calcium plus 400 IU vitamin D3 daily or placebo. Over seven years of follow up, results showed no difference in the development of diabetes in the treatment group compared to the placebo group. The authors pointed out, though, that the dose of vitamin D used in the study may have been too low, and higher doses may be needed to observe an impact on the risk of diabetes.6

Additionally, a meta-analysis of fifteen randomized controlled trials comparing vitamin D supplementation to placebo found that vitamin D supplementation in patients with diabetes had a small effect on fasting glucose and resulted in a small improvement in insulin resistance, but had no effect on HbA1c. Included studies, however, were only of moderate quality.7

Low vitamin D levels have also been linked to increased risk for micro- and macrovascular complications in diabetes. The five-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial found a higher incidence of micro- and macrovascular events in patients with T2DM and vitamin D levels <50 nmol/L, compared to those with levels ≥50 nmol/L.8 Studies have also implicated low vitamin D levels with diabetic peripheral neuropathy, diabetic foot ulcers, diabetic nephropathy, and diabetic retinopathy.4 Studies conflict, though, about whether vitamin D supplementation can play a role in decreasing the development of diabetic complications.

While much evidence implicates low vitamin D levels in the development of diabetes and its complications, conclusive evidence is hindered by a lack of studies with sufficient sample size, long enough time frames, and suboptimal doses of vitamin D. To determine the value of vitamin D supplementation in diabetes, larger, good quality randomized controlled trials are needed using optimal, therapeutic doses of vitamin D (about 4000 IU/day).6 In the meantime, as far as diabetes is concerned, there may be nothing more to fun in the sun than happy memories and a tan (but hopefully not a sunburn).  

Take-home Points

• Observational studies have linked low vitamin D levels to the development of diabetes and diabetic complications.

• Vitamin D plays multiple physiological roles that may have an impact on insulin secretion, insulin resistance, pancreatic beta cell function, and the development of diabetes.

• Research has yet to confirm that vitamin D supplementation improves glycemic control, or prevents the development of diabetes and its complications.

• To determine the value of vitamin D supplementation in diabetes, larger, good quality randomized controlled trials are needed using optimal, therapeutic doses of vitamin D.

 

References:

1. Nakashima A, et al. Role of vitamin D in diabetes mellitus and chronic kidney disease. World J Diabetes. 2016 Mar 10;7(5):89-100.

2. Afzal S, et al. Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem. 2013 Feb;59(2):381-391.

3. Song Y, et al. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care. 2013 May;36(5):1422-1428.

4. Alam U, et al. Vitamin D and diabetic complications: true or false prophet? Diabetes Ther. 2016 Mar;7(1):11-26.

5. Al-Shoumer KA, Al-Essa TM. Is there a relationship between vitamin D with insulin resistance and diabetes mellitus? World J Diabetes. 2015 Jul 25;6(8):1057-1064.

6. de Boer IH, et al. Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women's Health Initiative. Diabetes Care. 2008 Apr;31(4):701-707.

7. George PS, et al. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta-analysis. Diabet Med. 2012 Aug;29(8):e142-150.

8. Herrmann M, et al. Serum 25-hydroxyvitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care. 2015 Mar;38(3):521-528.