Diabetic Neuropathy assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy

Background: Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes is declining but it is not known if this is true also for diabetic neuropathy. Aim: To investigate the relationship between large fiber diabetic neuropathy and other diabetic complications. Materials and methods: Neuropathy, defined here as large fiber neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot using a standard VibroSense Meter and/or neuropathic symptoms, in 599 type 1 diabetic individuals. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications, were registered. Results: Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control persons without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two persons out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7x10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001). Conclusions: Despite recent changes in the incidence of diabetic complications, the onset of large fiber neuropathy follows that of retinopathy but precedes the onset of nephropathy in type 1 diabetes.