Effect of Escalating Oral Vitamin D Replacement on HOMA-IR in Vitamin D Deficient Type 2 Diabetics
Condition: Vitamin D Deficiency; Insulin Resistance; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2; Insulin Resistance; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      In addition to its effect on maintaining calcium homeostasis and mineralization of bone,
      vitamin D has been linked to play a pivotal role in different medical conditions including
      type 2 diabetes mellitus. Vitamin D plays a major role in both insulin secretion and
      decreasing the insulin resistance hence has a major impact on glucose tolerance. This study
      is designed to determine the non-skeletal effects of vitamin D in improving the glucose
      tolerance in type 2 diabetic patients by decreasing the insulin resistance
    

Detailed description: 
      Pakistan stands at seventh spot amongst the world having patients suffering from Type 2
      Diabetes Mellitus (T2DM) with the prevalence of approximately 6.9 million in 2007.

      Among the risk factors for the development of T2DM, there is a growing evidence that
      deficiency of vitamin D is an independent risk factor for its development and poor glycemic
      control. Vitamin D plays a significant role not only in secretion of insulin from the beta
      cells of pancreas but it also helps in decreasing the insulin resistance at the level of
      target cells.

      Vitamin D has received an enormous attention recently. A report from Australia indicated 1 in
      3 Australians are Vitamin D deficient. Reports from Pakistan have also demonstrated Vitamin D
      deficiency. The study conducted by Haroon Khan et al had 562 (76.2%) females while 175
      (23.8%) were males. Mean age of respondents was 36.3 years (age range 15-75 years. Females
      had significantly lower mean Vitamin D levels (56.2%) compared to males (15.3%).

      25(OH) Vitamin D is the circulating form of vitamin D which is measurable in the blood.
      Vitamin D insufficiency has been defined as serum 25-hydroxyvitamin D (25(OH) D) levels below
      30 ng/mL and it is common among patients with T2DM. Many studies have revealed that Vitamin
      D3 (calcitriol) has a role in the synthesis and the secretion of insulin by receptor mediated
      molecular mechanisms.

      Moreover Vitamin D functions are not limited to skeletal health benefits and may extend to
      preservation of insulin secretion and insulin sensitivity. Studies have revealed the
      association between vitamin D deficiency and changes in blood glucose and insulin levels as
      well as sensitivity of the target tissues to insulin .Cross-sectional data provide some
      evidence that circulating 25-hydroxyvitamin D (25(OH) D) is inversely associated with insulin
      resistance, although direct measurements of insulin sensitivity are required for
      confirmation. Available prospective studies support a protective influence of high 25(OH) D
      concentrations on type 2 diabetes mellitus risk. Vitamin D receptor gene polymorphisms and
      vitamin D interactions with the insulin like growth factor system may further influence
      glucose homeostasis. The ambiguity of optimal vitamin D dosing regimens and optimal
      therapeutic concentrations of serum 25(OH) D limit available intervention studies.

      A study found no improvement in glucose tolerance following the administration of two vitamin
      D doses with an interval of 2 weeks to thirty-seven non-diabetic, vitamin D-deficient adults.

      Another study reported a randomised, controlled trial of vitamin D3, three fortnightly doses
      of 120 000 IU or placebo, in centrally obese Indian men. The subjects were not necessarily
      insulin resistant, but there was some improvement in postprandial insulin sensitivity
      following supplementation. A recent systematic review and meta-analysis on the role of
      vitamin D and calcium in type 2 diabetes conclude that 'there appears to be a relationship'
      but due to the paucity of data, an understanding of the mechanisms is incomplete.

      This study has a novelty in the dosage and the frequency of administration of vitamin D which
      has not been studied yet. This study will enable to determine the impact of vitamin D
      replacement on insulin resistance in vitamin D deficient Type 2 diabetic patients and to find
      any correlation of serum levels of 25 hydroxyvitamin D levels with the degree of insulin
      resistance.
    

Intervention name(s): oral vitamin D
Intervention type(s): Drug
Intervention description(s): oral Vitamin D 400IU will be given and will be escalated every 2 weeks.
Other intervention name(s): oral vitamin D 400IU
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Vitamin D; T2DM; Insulin Resistance