Effect of Vitamin B12 Supplementation on Glycaemic Control in Uncontrolled Hyperhomocysteinemic Type 2 Diabetic Patients
Condition: Type 2 Diabetes; Vitamin B12 Deficiency; Hyperhomocysteinemia
MeSH terms: Hyperhomocysteinemia; Vitamin B 12 Deficiency
Study type: Interventional

Summary: 
      Increased plasma homocysteine level is associated with macroangiopathy and nephropathy in
      type 2 diabetes. Also increased levels of serum homocysteine are associated with
      microalbuminuria which is associated with increased cardiovascular morbidity and mortality
      among the patients with type 2 diabetes. With B12 supplementation homocysteine level can be
      reduced .Type 2 diabetes as a metabolic syndrome may show improvement in glycaemic control
      with Vitamin B12 therapy as there is correction of hyperhomocysteinemia. In studies it is
      proved that combination of vit B12, folic acid and vit B6 are effective for
      hyperhomocysteinemia.There are no such separate trials on the use of vit B12 alone. This
      therapy may be used in large number of type 2 uncontrolled diabetic hyperhomocysteinemic
      patients.

      this study was planned with following objectives to study effect of Vitamin B12
      supplementation on glycaemic control in poorly controlled hyperhomocysteinemic type 2
      diabetic patients

        1. Glycaemic control measured by levels of glycosylated haemoglobin (HbA1c) at baseline and
           4 weeks

        2. Fasting blood sugar level at baseline and 4 weeks

        3. Serum homocysteine/ vitamin B12 levels at baseline and 4 weeks

        4. Serum lipid profile at baseline and 4 weeks
    

Detailed description: 
      After approval from Institutional Ethics Committee, patients not responding adequately to
      oral anti-diabetic agents were recruited from Medicine out patient department (OPD) with the
      help of treating physician. Patient were first screened for serum homocysteine/vitamin B12
      level along with all baseline investigations. Those having serum homocysteine level more than
      15 umol/L or vitamin B12 level less than 223pg/ml were enrolled in this study. Due to high
      cost for investigation serum homocysteine level was measured only in 6 patients and serum
      vitamin B12 level (cheaper test) was measured in 14 patients with prior permission from
      Ethics Committee. Patients were given all the information about Vitamin B12 (methylcobalamin)
      including adverse effects. A written informed consent was taken from each patient and those
      who were willing to participate in study were enrolled in this study. All the information was
      recorded in case report forms.

      There were two groups of poorly controlled patient; one group (DRUG GROUP) received
      methylcobalamin 500 ug daily with their usual antidiabetic therapy and the other group
      (CONTROL GROUP) received suitable antidiabetic drug therapy as prescribed by treating
      physician. Methylcobalamin 500ug was given once daily for the period of 4 weeks and were
      followed-up at 4 weeks. At Baseline all the investigations were carried out as follows:

      Study Flow Chart

      Baseline Serum Homocysteine.n=6 (DRUG GROUP), Serum Vitamin B12, n=14 (DRUG GROUP), n=18
      (CONTROL GROUP) Body weight, height, Blood pressure,glycosylated hemoglobin (HbA1c) level,
      Blood sugar-Fasting/Postprandial, Serum lipid profile( to measure the effect of Vitamin B12),
      Blood urea, Serum creatinine, Serum Bilirubin, Serum glutamate oxaloacetate transaminase
      (SGOT),Serum glutamate pyruvate transaminase (SGPT), Alkaline phosphatase ( to rule out
      hepatic or renal dysfunction ), Routine urine examination for albumin, Electrocardiogram
      (ECG):to rule out cardiac abnormality viz, IHD, arrhythmias

      4 Weeks Body weight, Blood pressure, glycosylated hemoglobin(HbA1c) level, Blood
      sugar-Fasting/Postprandial, Serum lipid profile, Serum homocysteine/ serum vitamin B12, Urine
      albumin examination

      After enrollment of patient for study, All the baseline investigations will be carried out at
      Central Clinical Laboratory except glycosylated haemoglobin which was carried out at
      department of Pharmacology and homocysteine estimation which was carried out in an accredited
      laboratory. ECG, Blood pressure recording was carried out in Department of Medicine.

      Reporting of Adverse effects: All patients had been given checklist of adverse effect of
      vitamin B12. Information of adverse drug reactions (ADRs ) was taken in next follow-up. If
      patients are unable tolerate adverse drug reactions they were advised to contact any of
      investigators at any time. Contact numbers of investigators was mentioned on patient
      information sheet.

      Expected adverse drug reactions of vitamin B12 : Anorexia, Nausea, Vomiting, Diarrhea and
      Rash

      Sample Size Calculation and statistical analysis:

      Sample size of 20 for each group was calculated in the ratio of 1, power 80 %, considering 10
      fold difference of drug effect in vitamin B12 group and control group by using Open Epi
      2.3(2009). Randomization was done with the help of randomization software Rando 1.2,2004.
      Statistical analysis was done by using Open Epi 2.3(2009) and Microsoft Excel.
    

Intervention name(s): METHYLCOBALAMIN 500 micrograms
Intervention type(s): Dietary Supplement
Intervention description(s): Tab Methycobalamin 500 ug will be given with other regular antidiabetic drugs
Other intervention name(s): Vitamin B12
Intervention MeSH terms: Vitamin B 12
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment