Diabetes Intervention Trial With Vitamin D in Subjects of Nordic and Sub-Indian Ethnicity (DIVINE)

• Insulin secretion measured with IVGTT [ Time Frame: At 0 and 6 months ] [ Designated as safety issue: No ]
• Physical activity/muscle strength [ Time Frame: At 0 and 6 months ] [ Designated as safety issue: No ]
• HbA1c and fasting glucose [ Time Frame: At 0, 3 and 6 months ] [ Designated as safety issue: No ]
• Arterial stiffness [ Time Frame: At 0 and 6 months ] [ Designated as safety issue: No ]
• Differences in inflammatory markers, endothelial function and bone specific laboratory markers. [ Time Frame: At 0, 3 and 6 months ] [ Designated as safety issue: No ]
• Safety of this regimen of vitamin D3 supplementation; subjects will be assessed for hypercalcemia and renal dysfunction. [ Time Frame: Entire intervention period, samples taken at 0,1,3, and 6 months ] [ Designated as safety issue: Yes ]
• Change from baseline in quality of life score between groups (SF-36). [ Time Frame: At 0 and 6 months ] [ Designated as safety issue: No ]
• Effect on serum lipid levels and other biochemical markers [ Time Frame: At 0, 3 and 6 months ] [ Designated as safety issue: No ]
• Metabolomics analyses. [ Time Frame: At 0 and 6 months ] [ Designated as safety issue: No ]

The aim of this 6 months study is to evaluate the metabolic effects of 400.000-600.000 IU of vitamin D supplementation in subjects with type 2 diabetes and hypovitaminosis D. The main hypothesis is that subjects with low levels of 25-OH-vitamin D will benefit from supplementation with cholecalciferol in sufficient doses to optimize serum levels.

Accumulating evidence suggests that hypovitaminosis D may be associated with the development of type 2 diabetes and disturbances in glucose and insulin metabolism. There is lack of data from randomized, controlled studies of sufficient duration and with the use of sufficient doses of vitamin D to assess the importance of vitamin D supplementation in glucose metabolism in type 2 diabetes.

• Diabetes Mellitus Type 2
• Hypovitaminosis D

• Drug: Cholecalciferol
  Cholecalciferol 200.000 IU pr ampoule, 400.000 IU given at randomization day, followed by additionally 200.000 IU at week 5 if serum 25(OH)D < 100 nmol/L. If serum 25(OH)D > 100 placebo will be given. The cholecalciferol will be given in orange juice.
  Other Names:

  • Vitamin D
  • ZymaD
• Other: Orange juice
  Orange juice at randomization day and at week 5.

• Experimental: Cholecalciferol
  Intervention: Drug: Cholecalciferol
• Placebo Comparator: Placebo
  Intervention: Other: Orange juice

Inclusion criteria:

1. Moderate (S-25OHD 25-50 nmol/l) to severe (S-25OHD < 25 nmol/l) vitamin D deficiency measured at Visit 1.
2. Patients with type 2 diabetes, including drug naïve subjects, subjects using oral anti-diabetic medication and subjects on insulin treatment. All medication must be in stable doses during the 4 week lead-in period.
3. HbA1c < 11 % at Visit 1.
4. Able to communicate in Norwegian.
5. Men and women ≥ 18 years.
6. Norwegian or South Asian ethnicity.
7. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study. All WOCBP must have negative serum or urine pregnancy test at enrollment, randomization, titration visit and final study assessment.
8. Antihypertensive medication, lipid lowering drugs, oral contraceptives, hormone replacement therapy, multivitamin supplements and nutritional supplements are allowed if the subjects adhere to the same regimen during the study

Exclusion Criteria:

1. Subjects not having type 2 diabetes.
2. SBP ≥ 160 or DBP ≥ 95 at Visit 1.
3. Significant renal disease or chronic renal impairment, GFR< 30 ml/min.
4. Significant liver disease or ASAT or ALAT >3x UNL.
5. Malignancy during the last five years.
6. Hypercalcemia at Visit 1.
7. A history of kidney stone disease
8. WOCBP unwilling or unable to use an acceptable method to avoid pregnancy.
9. Pregnant or breastfeeding women.
10. Chronic inflammatory disease in active phase
11. Long term (>2 weeks) use of corticosteroids last 3 months
12. Mental condition (psychiatric or organic cerebral disease) rendering the subject unable to understand the nature, scope and possible consequences of the study.
13. Drug or alcohol abuse.
14. BMI > 45 kg/m2 or bariatric surgery (<5 years).
15. Anemia
16. Cardiovascular disease (myocardial infarction, unstable angina pectoris or stroke) during the last 6 months.
17. Any medical condition that in the judgment of the investigator would jeopardize the subject's safety or evaluation of the study drug for efficacy and safety.