Thiazolidinedione Intervention With Vitamin D Evaluation

This study will answer two separate questions.

The first question is to test the cardiovascular effects of long-term treatment with rosiglitazone or pioglitazone when used as part of standard of care compared to similar standard of care without rosiglitazone or pioglitazone in patients with type 2 diabetes who have a history of or are at risk for cardiovascular disease.

The second question will compare the effects of long-term supplementation of vitamin D on death and cancer


Eligibility Criteria:
Inclusion Criteria:

* Men or women with: a) newly detected type 2 diabetes based on a fasting plasma glucose greater than or equal to 7.0 mmol/l (126 mg/dL) or a 2 hour plasma glucose (FPG) greater than or equal to 11.1 mmol/l (200 mg/dL) on an oral glucose tolerance test, or b) a history of type 2 diabetes
* Hemoglobin A1c (A1C) 6.5-9.5% inclusive (for assays with upper limit of normal of 6%) within one month of screening
* Age ≥ 50 years and evidence of vascular disease defined as ≥1of:

  * prior myocardial infarction
  * prior stroke
  * coronary, carotid or peripheral artery revascularization ≥ 4 years earlier
  * previous documented myocardial ischemia on either an exercise stress test or on any cardiac imaging, or previous unstable angina with ECG changes or cardiac enzyme elevation OR
* Age ≥ 55 years and evidence of subclinical vascular disease defined as ≥1 of:

  * microalbuminuria or proteinuria
  * history of treated or untreated hypertension with left ventricular hypertrophy by electrocardiogram (ECG) or echocardiogram

    * 50% stenosis on any imaging of coronary, carotid or lower extremity arteries
  * ankle/brachial index \<0.9 OR
* Age ≥ 60 years and at least 2 of the following cardiovascular disease risk factors:

  * current tobacco use
  * LDL-c ≥3.4 mmol/L (130 mg/dL) or on a lipid lowering medication
  * HDL-c \< 1.0 mmol/L (40 mg/dL) for men and \< 1.3 mmol/L (50 mg/dL) for women or triglycerides ≥ 2.3 mmol/L (200 mg/dL)
  * BP lowering medication use or untreated SBP ≥ 140 mmHg or DBP ≥ 95 mmHg
  * Waist to hip ratio \> 1.0 for men and \> 0.8 for women
* On no insulin and on less than or equal to 2 anti-diabetes drugs where at least one drug is at or below the half-maximal dose (as indicated in the MOP) with stable dosing for 10 weeks prior to screening

Exclusion Criteria:

* Type 1 diabetes
* Current need for insulin treatment
* Symptomatic hyperglycemia requiring immediate therapy in the judgment of the physician
* An acute cardiovascular event within 30 days prior to randomization
* Symptomatic heart failure (i.e. New York Heart Association class II or higher) or any episode of previous pulmonary edema or known ejection fraction \< 0.4 or current use of loop diuretics
* Any fracture within the past 1 year
* Currently planned coronary, carotid or peripheral artery revascularization or cardiac valve surgery
* Coronary, carotid or peripheral artery revascularization within the 4 years prior to screening in the absence of angina, MI, or stroke in the intervening period
* End stage renal disease requiring renal replacement therapy
* Receiving drug therapy to treat liver disease
* A diagnosis of cancer (other than superficial squamous, basal cell skin cancer, or adequately treated cervical carcinoma in situ) in the past 3 years or current treatment for the active cancer (other than prophylactic)
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \> 2.5 times the upper limit of normal
* A prior heart transplant or awaiting a heart transplant
* Previous or current hypercalcemia, hyperparathyroidism, osteomalacia or other contraindication for vitamin D therapy
* Regular use of or indication for greater than 400IU of vitamin D daily
* Clinically or medically unstable with expected survival \< 1 year
* Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data
* Any other factor likely to limit protocol compliance or reporting of adverse events
* Inability to discontinue a TZD (if taking one) in the judgement of the physician/investigator
* Contraindications to or history of hypersensitivity to the investigational products
* History of renal stones within the past 2 years
* Participation in another clinical trial of an investigational agent