Influence of Nitrates on Bone Remodeling and Endothelial Function in Patients With Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) is becoming a leading global epidemic. DM affects several systems in the body. Most of the complications encountered in DM are attributed to uncontrolled hyperglycemia or poor glycemic control. Hyperglycemic stress tends to damage the inner lining of the small blood vessels (endothelium). Normally, the endothelium releases a chemical substance called nitric oxide (NO) which relaxes the blood vessels and also prevents blockade of these vessels. Therefore damage to the endothelium (endothelial dysfunction) results in diminished levels of NO which ultimately leads to occlusion of these small blood vessels (microvascular occlusion). Microvascular occlusion of vessels supplying the eyes, kidneys and nerves leads to serious complications like diabetic retinopathy, nephropathy and neuropathy. Of late, the skeletal system has emerged as another vulnerable target of diabetic microvascular disease. Patients with DM have an increased risk of developing fractures. Certain predisposing factors like diabetic neuropathy and visual disturbances (retinopathy and cataract) increases the likelihood of fractures in DM. More recently, evolving research has demonstrated NO\'s prospective role in bone preservation. Earlier studies have also validated the use of nitrates (donor of NO) in improving bone strength and reducing the risk of fractures. So far no study has investigated the effect of nitrates on endothelial function and bone microarchitecture in patients with diabetes. The investigators therefore propose to investigate the influence of nitrates on endothelial dysfunction and bone integrity in patients with type 2 diabetes. 40 patients with type 2 DM will be recruited into the study; 20 patients will receive 20 mg of oral isosorbide mononitrate daily and the other 20 will not receive the study drug. The investigators hope to demonstrate an improvement in endothelial function (by measuring skin blood flow) and bone integrity (by measuring markers of bone formation and bone resorption and bone mineral density - BMD) following 6 months of nitrate therapy.