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The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review. PMID: 17389701 .CONCLUSIONS: Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.

Vitamin D and diabetes: improvement of glycemic control with vitamin D3 repletion. Schwalfenberg G. Can Fam Physician. 2008 Jun;54(6):864-6. PMID: 18556494 Conclusion These cases support information that is already known about VTD and its effect on the islet cell. As discussed above, this might be true only for vitamin D3 and not vitamin D2, although vitamin D2 has been shown to improve bone health. Vitamin D insufficiency or deficiency is common, and repletion might improve glycemic control early in type 2 diabetes. Diabetes is one of the fastest growing chronic diseases worldwide. Vitamin D3 is inexpensive and readily available. Well-designed clinical studies are required to ascertain if improving 25(OH)D levels from an insufficiency or deficiency to sufficiency improves glycemic control in diabetes. These studies need to be properly designed: a randomized controlled trial with VTD deficiency or insufficiency identified in diabetic patients of various ethnic

Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Diabetes. 2008 Oct;57(10):2619-25. Epub 2008 Jun 30. PMID: 18591391 doi: 10.2337/db08-0593 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.

Vitamin D and type 2 diabetes: are we ready for a prevention trial? Scragg R. Diabetes. 2008 Oct;57(10):2565-6. PMID: 18820212 doi: 10.2337/db08-0879 Despite evidence from the current article (3) and the Finnish study (17), doubts still remain about whether low vitamin status is a cause of type 2 diabetes. Further cohort studies are required, assessing baseline vitamin D status using blood 25(OH)D to be sure that the Ely and Finnish studies are not false-positive results. Glucose clamp studies are also required because we are still not sure of the mechanism influenced by vitamin D-whether it is insulin resistance, secretion, or both. But most importantly, given that nearly three decades have passed since the first studies linking vitamin D with insulin metabolism (6,7), well-designed clinical trials of the effect of vitamin D supplementation on glycemia status and diabetes risk are urgently required to settle this question. And they need to prevent past mistakes. In particular, the vitamin D dose given in such trials needs to be high enough-above 2,000 IU per day (19)-to raise blood 25(OH)D levels above 80 nmol/l because diabetes risk is lowest at this level (9,20). If well-designed trials are carried out and confirm a protective effect from vitamin D, it could be used by the general population as a simple and cheap solution to help prevent the diabetes epidemic.

Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF. J Nutr. 2009 Feb;139(2):329-34. Epub 2008 Dec 23. PMID: 19106328 doi:10.3945/jn.108.093831 After adjusting for age and sex, plasma 25(OH)D was positively associated with ISI(0,120), plasma adiponectin, and HDL cholesterol and inversely associated with plasma triacylglycerol, but these associations were no longer significant after further adjustment for BMI, waist circumference, and current smoking status. 25(OH)D and 2-h post-OGTT glucose were not associated. Among adults without diabetes, vitamin D status was inversely associated with surrogate fasting measures of insulin resistance. These results suggest that vitamin D status may be an important determinant for type 2 diabetes mellitus.

Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Hjelmesaeth J, Hofsø D, Aasheim ET, Jenssen T, Moan J, Hager H, Røislien J, Bollerslev J. Cardiovasc Diabetol. 2009 Feb 3;8:7. PMID: 19187564 doi:10.1186/1475-2840-8-7 CONCLUSION: The PTH level, but not the vitamin D level, is an independent predictor of MS in treatment seeking morbidly obese Caucasian women and men. Randomized controlled clinical trials, including different therapeutic strategies to lower PTH, e.g. calcium/vitamin D supplementation and weight reduction, are necessary to explore any cause-and-effect relationship.

Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Jorde R, Figenschau Y. Eur J Nutr. 2009 Apr 16. [Epub ahead of print] PMID: 19370371 10.1007/s00394-009-0020-3 Conclusions We were not able to demonstrate that vitamin D supplementation had a significant effect on glucose metabolism in subjects with type 2 diabetes but without vitamin D deficiency. Further studies are needed in larger groups of subjects with type 2 diabetes or impaired glucose tolerance, who also exhibit low serum 25-hydroxyvitamin D levels.

Serum vitamin D and subsequent occurrence of type 2 diabetes. Knekt P, Laaksonen M, Mattila C, Härkänen T, Marniemi J, Heliövaara M, Rissanen H, Montonen J, Reunanen A. Epidemiology. 2008 Sep;19(5):666-71. PMID: 18496468 doi: 10.1097/EDE.0b013e318176b8ad Conclusions: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association.

Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Mattila C, Knekt P, Männistö S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A. Diabetes Care. 2007 Oct;30(10):2569-70. Epub 2007 Jul 12. PMID: 17626891 doi: 10.2337/dc07-0292 We found a significant inverse association between serum 25OHD and risk of type 2 diabetes in the simple model. However, the association was attenuated in the multivariate analysis, adjusting for potential risk factors of type 2 diabetes. To our knowledge, this is the first cohort study investigating the association between serum 25OHD and incidence of type 2 diabetes. Our results are in line with those from the Nurses' Health Study (5), where an inverse association was observed for the intake of vitamin D supplements. We could not differentiate whether the results depended on the effect of vitamin D deficiency on β-cell function or on insulin resistance. In summary, the results are in line with the hypothesis that a high serum 25OHD concentration may reduce the risk of type 2 diabetes. Further research is needed to confirm the association and to distinguish between the independent role of vitamin D and the role of healthy dietary and lifestyle patterns in reducing the risk of type 2 diabetes.

Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, Arcaro G. Clin Endocrinol (Oxf). 2006 Nov;65(5):593-7. PMID: 17054459 DOI: 10.1111/j.1365-2265.2006.02633.x CONCLUSIONS: Hypovitaminosis D is highly prevalent in type 2 diabetic adults and is strongly and independently associated with increased carotid IMT. Further investigation into whether vitamin D may play a role in the prevention of atherosclerosis appears to be warranted. In conclusion, our results show that type 2 diabetic adults have significant reductions in serum 25(OH)D concentrations (vs matched controls) that predict preclinical atherosclerosis, independent of classical risk factors, renal function tests, inflammatory markers, use of medications and presence of the metabolic syndrome. These findings suggest the need for ongoing evaluation of the possible protective role of vitamin D3 supplementation in the development of atherosclerosis.

Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Chiu KC, Chu A, Go VL, Saad MF. Am J Clin Nutr. 2004 May;79(5):820-5. PMID: 15113720 Conclusions: The data show a positive correlation of 25(OH)D concentration with insulin sensitivity and a negative effect of hypovitaminosis D on ß cell function. Subjects with hypovitaminosis D are at higher risk of insulin resistance and the metabolic syndrome. Further studies are required to explore the underlying mechanisms.

25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Hyppönen E, Boucher BJ, Berry DJ, Power C. Diabetes. 2008 Feb;57(2):298-305. Epub 2007 Nov 14. PMID: 18003755 doi: 10.2337/db07-1122 CONCLUSIONS-Serum 25(OH)D is inversely associated with metabolic syndrome, whereas the inverse association with IGF-1 was found only among those without hypovitaminosis D. These results suggest that metabolic syndrome prevalence is the lowest when both 25(OH)D and IGF-1 are high.

1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus. Oh J, Weng S, Felton SK, Bhandare S, Riek A, Butler B, Proctor BM, Petty M, Chen Z, Schechtman KB, Bernal-Mizrachi L, Bernal-Mizrachi C. Circulation. 2009 Aug 25;120(8):687-98. Epub 2009 Aug 10. PMID: 19667238 doi: 10.1161/CIRCULATIONAHA.109.856070 Conclusion- These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.

ScienceDaily (Aug. 25, 2009) - Low levels of vitamin D are known to nearly double the risk of cardiovascular disease in patients with diabetes, and researchers at Washington University School of Medicine in St. Louis now think they know why. They have found that diabetics deficient in vitamin D can't process cholesterol normally, so it builds up in their blood vessels, increasing the risk of heart attack and stroke. The new research has identified a mechanism linking low vitamin D levels to heart disease risk and may lead to ways to fix the problem, simply by increasing levels of vitamin D.

Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Palomer X, González-Clemente JM, Blanco-Vaca F, Mauricio D. Diabetes Obes Metab. 2008 Mar;10(3):185-97. Review. PMID: 18269634 DOI: 10.1111/j.1463-1326.2007.00710.x Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. It has been reported that vitamin D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes mellitus. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D, thereby suggesting a role for vitamin D in the pathogenesis of type 2 diabetes mellitus.

In conclusion, genetic variations of DBP are associated with insulin resistance in Japanese with normal glucose tolerance, which might contribute to the development of type 2 diabetes. Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance. Hirai M, Suzuki S, Hinokio Y, Hirai A, Chiba M, Akai H, Suzuki C, Toyota T. J Clin Endocrinol Metab. 2000 May;85(5):1951-3. PMID: 10843180

Not enough vitamin D: health consequences for Canadians. Schwalfenberg G. Can Fam Physician. 2007 May;53(5):841-54. Review PMID: 17872747 Conclusion Low levels of VTD are considered a major public health problem in Canada, especially during the winter. Those with risk factors should be screened for low 25(OH)D levels and repletion therapy instituted if needed. Researchers have estimated that the oral dose of vitamin D3 to attain and maintain 25(OH)D levels >80 nmol/L is 2200 IU/d if baseline levels are 20 to 40 nmol/L, 1800 IU/d if levels are 40 to 60 nmol/L, and 1160 IU/d if levels are between 60 and 80 nmol/L.64 We need to ensure that patients have healthy blood levels of 25(OH)D to prevent levels of parathyroid hormone from rising and to maximize absorption of calcium, magnesium, and phosphate. Positive effects on bone are marginal at best unless patients consume at least 800 IU/d of VTD. The emerging and exciting role of the VTD receptor and the actions of VTD in maintaining health in other cell types have become more apparent during the last decade.

March 11, 2009 -- Low vitamin D levels greatly increase a teenager's risk of diabetes and heart disease, Johns Hopkins researchers find. It is becoming clear that adults who get too little vitamin D are at higher risk for diabetes and heart disease. Now, it appears vitamin D levels also affect these risks earlier in life, say Johns Hopkins researchers Jared P. Reis, PhD, and colleagues.

Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. Epub 2007 Mar 27. Review. PMID: 17389701 [PubMed - indexed for MEDL

Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, Arcaro G. Clin Endocrinol (Oxf). 2006 Nov;65(5):593-7. PMID: 17054459 CONCLUSIONS: Hypovitaminosis D is highly prevalent in type 2 diabetic adults and is strongly and independently associated with increased carotid IMT. Further investigation into whether vitamin D may play a role in the prevention of atherosclerosis appears to be warranted.