One of the major challenges of studying and treating diabetes mellitus, a chronic degenerative disease, is the extremely long time horizon involved in the development of its complications. Our understanding of this time course has largely been through the study of type 1 diabetes mellitus (T1DM), in which the onset of abnormal glycemia can be accurately timed and there are relatively few coincident mediators of disease.
The earliest clinically detectable signs of retinopathy, such as microaneurysms, do not usually occur until at least 5 years after development of T1DM. More advanced stages of retinopathy, including preproliferative retinopathy, require at least 10 years, and macular edema and proliferative retinopathy, which can lead to loss of vision, do not usually occur until 15 to 20 years of T1DM duration. Similarly, nephropathy and neuropathy usually manifest initially subclinically, with microalbuminuria and abnormal electrophysiologic findings, respectively.1 They advance over time to albuminuria and physical findings including diminished thresholds for vibration and light touch sensation. These subclinical and early clinical findings are by themselves not clinically significant; however, with time they can progress to further injury and loss of function with severe clinical consequences. The development of end-stage kidney disease requiring dialysis or a transplant usually takes 25 years or more of T1DM duration.