Early Detection of Diabetic Microvascular Complications: the Key to Improving Outcomes*

Perhaps the strongest argument for early detection of diabetic microvascular complications is the finding that 50% of all patients with type 2 diabetes mellitus already have signs of at least 1 diabetic microvascular or macrovascular complication at the time of diagnosis. Prevention of diabetic nephropathy hinges on monitoring; screening for hypertension, poor glucose control, and microalbuminuria (3 treatable risk factors); and instituting or modifying therapy as necessary. Because patients with diabetic nephropathy are at an increased risk for cardiovascular disease, cardiovascular risk factors such as hyperlipidemia should also be monitored and controlled when nephropathy is identified. The importance of glucose control can best be emphasized by findings that a 1% reduction in glycosylated hemoglobin can result in a 21% to 57% reduction in diabetic microvascular complications. The role of the renin-angiotensin system in hypertension and diabetic nephropathy should also be acknowledged, particularly because agents that effectively block this system (the angiotensin-converting enzyme inhibitors and the angiotensin II receptor blockers) are available. Every 10-mm Hg decrement in mean systolic blood pressure reduces the risk for all microvascular endpoints by 13%. Several other pathways have been implicated in the pathogenesis of diabetic microvascular complications, raising the possibility that newer therapies directed at these pathways may improve outcome. Inhibition of the protein kinase C (PKC) pathway appears to be most promising; ruboxistaurin, an orally active PKC-β inhibitor, is currently being evaluated in clinical trials involving patients with diabetic nephropathy, diabetic peripheral neuropathy, diabetic retinopathy, and diabetic macular edema. Results from earlier animal studies and clinical studies with this agent have been encouraging, and results of the current trials are eagerly awaited. (Adv Stud Med. 2005;5(3A):S159-S166)