Download PDF
Horm Metab Res 2014; 46(01): 54-58
DOI: 10.1055/s-0033-1358453
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Effect of a Randomised Controlled Vitamin D Trial on Insulin Resistance and Glucose Metabolism in Patients with Type 2 Diabetes Mellitus

F. Strobel   *
1   Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, Goethe-University Hospital, Frankfurt am Main, Germany
,
J. Reusch   *
1   Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, Goethe-University Hospital, Frankfurt am Main, Germany
,
M. Penna-Martinez   *
1   Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, Goethe-University Hospital, Frankfurt am Main, Germany
,
E. Ramos-Lopez
1   Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, Goethe-University Hospital, Frankfurt am Main, Germany
,
E. Klahold
1   Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, Goethe-University Hospital, Frankfurt am Main, Germany
,
C. Klepzig
2   Diabetes Outpatient Clinic Offenbach and Frankfurt am Main, Germany
,
J. Wehrle
3   Pharmacy of the Goethe-University Hospital, Frankfurt am Main, Germany
,
H. Kahles   *
1   Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, Goethe-University Hospital, Frankfurt am Main, Germany
,
K. Badenhoop   *
1   Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine I, Goethe-University Hospital, Frankfurt am Main, Germany
› Author Affiliations
Further Information

Publication History

received 22 April 2013

accepted 26 September 2013

Publication Date:
06 November 2013 (online)

Also available at
   Permissions and Reprints

Abstract

The aim of our study was to investigate the influence of a 6-month vitamin D supplementation in patients with noninsulin-requiring type 2 diabetes mellitus. We included 86 patients in a placebo-controlled, randomised, double-blind study. During 6 months patients received Vigantol oil once a week corresponding to a daily dose of 1904 IU or placebo oil, followed by 6 months of follow-up. At start and at 3-month intervals 25OHD, PTH, body mass index, HbA1c, insulin, C-peptide, and homeostasis model assessment-index were measured. The primary outcome was a change in fasting blood glucose and insulin levels. After 6 months of therapy, the verum group’s 25OHD had increased to a median of 35 ng/ml in comparison to the placebo group (median 20 ng/ml, p<10−6). PTH tended to decrease in the verum group (25.5 pg/ml vs. 35.0 pg/ml, p=0.08). After 6 months of therapy, 31 patients (78%) achieved a 25OHD concentration of >20 ng/ml. Their HbA1c was significantly lower at baseline (p=0.008) and after therapy (p=0.009) than in patients with 25OHD below 20 ng/ml. C-Peptide, insulin, and HOMA-index did not change significantly in the verum group but fasting insulin was positively correlated with 25OHD concentrations after 6 months of therapy in both groups. There were no significant effects of vitamin D with a daily dose of 1904 IU on metabolic parameters in type 2 diabetes. However, the correlative findings of this study suggest a link of the 25OHD status and metabolic function in type 2 diabetes. Whether vitamin D therapy with higher doses can improve glucose metabolism needs to be investigated in follow-up trials.

Key words

diabetes - vitamin D - metabolism - HbA1c - C-peptide - insulin

* Equal contribution.


 

  • References

  • 1 Guariguata L, Whiting D, Weil C, Unwin N. The International Diabetes Federation diabetes atlas methodology for estimating global and national prevalence of diabetes in adults. Diabetes Res Clin Pract 2011; 94: 322-332
    CrossrefPubMedGoogle Scholar
  • 2 Guariguata L. By the numbers: new estimates from the IDF Diabetes Atlas Update for 2012. Diabetes Res Clin Pract 2012; 98: 524-525
    CrossrefPubMedGoogle Scholar
  • 3 Andersson EA, Allin KH, Sandholt CH, Borglykke A, Lau CJ, Ribel-Madsen R, Sparso T, Justesen JM, Harder MN, Jorgensen ME, Jorgensen T, Hansen T, Pedersen O. Genetic risk score of 46 type 2 diabetes risk variants associates with changes in plasma glucose and estimates of pancreatic beta-cell function over five years of follow-up. Diabetes 2013; 62: 3610-3617
    CrossrefPubMedGoogle Scholar
  • 4 Pittas AG, Nelson J, Mitri J, Hillmann W, Garganta C, Nathan DM, Hu FB, Dawson Hughes B. 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
    CrossrefPubMedGoogle Scholar
  • 5 Van Belle TL, Gysemans C, Mathieu C. Vitamin D and diabetes: the odd couple. Trends Endocrinol Metab 2013; [Epub ahead of print]
    PubMedGoogle Scholar
  • 6 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; 92: 2017-2029
    CrossrefPubMedGoogle Scholar
  • 7 Hintzpeter B, Mensink GB, Thierfelder W, Muller MJ, Scheidt-Nave C. Vitamin D status and health correlates among German adults. Eur J Clin Nutr 2008; 62: 1079-1089
    CrossrefPubMedGoogle Scholar
  • 8 Isaia G, Giorgino R, Adami S. High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 2001; 24: 1496
    CrossrefPubMedGoogle Scholar
  • 9 Mattila C, Knekt P, Mannisto S, Rissanen H, Laaksonen MA, Montonen J, Reunanen A. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care 2007; 30: 2569-2570
    CrossrefPubMedGoogle Scholar
  • 10 Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006; 29: 650-656
    CrossrefPubMedGoogle Scholar
  • 11 Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care 2005; 28: 1228-1230
    CrossrefPubMedGoogle Scholar
  • 12 Hypponen E, Boucher BJ, Berry DJ, Power C. 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes 2008; 57: 298-305
    PubMedGoogle Scholar
  • 13 Parikh SJ, Edelman M, Uwaifo GI, Freedman RJ, Semega-Janneh M, Reynolds J, Yanovski JA. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab 2004; 89: 1196-1199
    CrossrefPubMedGoogle Scholar
  • 14 Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J. The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res 2009; 29: 3713-3720
    PubMedGoogle Scholar
  • 15 McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J 2008; 7: 4
    CrossrefPubMedGoogle Scholar
  • 16 Rueda S, Fernandez-Fernandez C, Romero F, Martinez de OJ, Vidal J. Vitamin D, PTH, and the metabolic syndrome in severely obese subjects. Obes Surg 2008; 18: 151-154
    CrossrefPubMedGoogle Scholar
  • 17 Alvarez JA, Ashraf AP, Hunter GR, Gower BA. Serum 25-hydroxyvitamin D and parathyroid hormone are independent determinants of whole-body insulin sensitivity in women and may contribute to lower insulin sensitivity in African Americans. Am J Clin Nutr 2010; 92: 1344-1349
    CrossrefPubMedGoogle Scholar
  • 18 Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL, Robins SJ, O'Donnell CJ, Hoffmann U, Jacques PF, Booth SL, Vasan RS, Wolf M, Wang TJ. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes 2010; 59: 242-248
    CrossrefPubMedGoogle Scholar
  • 19 Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 2004; 79: 820-825
    PubMedGoogle Scholar
  • 20 Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990–2000. Diabetes 2008; 57: 2619-2625
    CrossrefPubMedGoogle Scholar
  • 21 Kayaniyil S, Vieth R, Retnakaran R, Knight JA, Qi Y, Gerstein HC, Perkins BA, Harris SB, Zinman B, Hanley AJ. Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care 2010; 33: 1379-1381
    CrossrefPubMedGoogle Scholar
  • 22 Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF. Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr 2009; 139: 329-334
    PubMedGoogle Scholar
  • 23 Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004; 27: 2813-2818
    CrossrefPubMedGoogle Scholar
  • 24 Zhao G, Ford ES, Li C. Associations of serum concentrations of 25-hydroxyvitamin D and parathyroid hormone with surrogate markers of insulin resistance among U.S. adults without physician-diagnosed diabetes: NHANES 2003–2006. Diabetes Care 2010; 33: 344-347
    CrossrefPubMedGoogle Scholar
  • 25 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
    CrossrefPubMedGoogle Scholar
  • 26 Sabherwal S, Bravis V, Devendra D. Effect of oral vitamin D and calcium replacement on glycaemic control in South Asian patients with type 2 diabetes. Int J Clin Pract 2010; 64: 1084-1089
    CrossrefPubMedGoogle Scholar
  • 27 von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient – a randomised, placebo-controlled trial. Br J Nutr 2010; 103: 549-555
    Google Scholar
  • 28 Hjelmesaeth J, Hofso D, Aasheim ET, Jenssen T, Moan J, Hager H, Roislien J, Bollerslev J. Parathyroid hormone, but not vitamin D, is associated with the metabolic syndrome in morbidly obese women and men: a cross-sectional study. Cardiovasc Diabetol 2009; 8: 7
    CrossrefPubMedGoogle Scholar
  • 29 Lippi G, Montagnana M, Targher G, Guidi GC. Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults: response to Reis et al. Diabetes Care 2007; 30: e135
    CrossrefPubMedGoogle Scholar
  • 30 Snijder M, van DR, Visser M, Deeg D, Seidell J, Lips P. To: Mathieu C, Gysemans C, Giulietti A, Bouillon R (2005) Vitamin D and diabetes. Diabetologia 48: 1247–1257. Diabetologia 2006; 49: 217-218
    CrossrefPubMedGoogle Scholar
  • 31 Avenell A, Cook JA, MacLennan GS, McPherson GC. Vitamin D supplementation and type 2 diabetes: a substudy of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). Age Ageing 2009; 38: 606-609
    CrossrefPubMedGoogle Scholar
  • 32 de Boer IH, Tinker LF, Connelly S, Curb JD, Howard BV, Kestenbaum B, Larson JC, Manson JE, Margolis KL, Siscovick DS, Weiss NS. Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women’s Health Initiative. Diabetes Care 2008; 31: 701-707
    CrossrefPubMedGoogle Scholar
  • 33 Luo C, Wong J, Brown M, Hooper M, Molyneaux L, Yue DK. Hypovitaminosis D in Chinese type 2 diabetes: lack of impact on clinical metabolic status and biomarkers of cellular inflammation. Diab Vasc Dis Res 2009; 6: 194-199
    CrossrefPubMedGoogle Scholar
  • 34 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281
    CrossrefPubMedGoogle Scholar
  • 35 Dupont WD, Plummer Jr WD. Power and sample size calculations. A review and computer program. Control Clin Trials 1990; 11: 116-128
    CrossrefPubMedGoogle Scholar
  • 36 Joergensen C, Gall MA, Schmedes A, Tarnow L, Parving HH, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care 2010; 33: 2238-2243
    CrossrefPubMedGoogle Scholar
  • 37 Grimnes G, Emaus N, Joakimsen RM, Figenschau Y, Jenssen T, Njolstad I, Schirmer H, Jorde R. Baseline serum 25-hydroxyvitamin D concentrations in the Tromso Study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow-up. Diabet Med 2010; 27: 1107-1115
    CrossrefPubMedGoogle Scholar
  • 38 Badenhoop K, Kahles H, Penna-Martinez M. Vitamin D, immune tolerance, and prevention of type 1 diabetes. Curr Diab Rep 2012; 12: 635-642
    CrossrefPubMedGoogle Scholar
  • 39 Cheng Q, Li YC, Boucher BJ, Leung PS. A novel role for vitamin D: modulation of expression and function of the local renin-angiotensin system in mouse pancreatic islets. Diabetologia 2011; 54: 2077-2081
    CrossrefPubMedGoogle Scholar
  • 40 George PS, Pearson ER, Witham MD. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta-analysis. Diabet Med 2012; 29: e142-e150
    CrossrefPubMedGoogle Scholar
  • 41 Rose K, Penna-Martinez M, Klahold E, Karger D, Shoghi F, Kahles H, Bayer M, Hintermann E, Pfeilschifter JM, Badenhoop K, Ramos-Lopez E, Christen U. Influence of the vitamin D plasma level and vitamin D-related genetic polymorphisms on the immune status of patients with type 1 diabetes: a pilot study. Clin Exp Immunol 2013; 171: 171-185
    CrossrefPubMedGoogle Scholar
  • 42 Breslavsky A, Frand J, Matas Z, Boaz M, Barnea Z, Shargorodsky M. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr 2013; [Epub ahead of print]
    PubMedGoogle Scholar
  • 43 Hossein-Nezhad A, Spira A, Holick MF. Influence of vitamin d status and vitamin d3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One 2013; 8: e58725
    CrossrefPubMedGoogle Scholar