Glucose variability does not contribute to the development of peripheral and autonomic neuropathy in type 1 diabetes: data from the DCCT

EMG Electromyography MAGE Mean amplitude of glycaemic excursionsTo the Editor: While it is suggested that, in addition to hyperglycaemia, glucose variability can contribute to the severity and development of diabetic neuropathy [1], it is not related to the development of retinopathy and nephropathy in type 1 diabetes [1,2].To determine any additional effect of glucose variability-above that assessed by HbA 1c and mean glucose-on peripheral and autonomic diabetic neuropathy, we used the datasets collected during the DCCT (available at www.gcrc.med.umn.edu/gcrc/downloads/dcct.html, accessed 23-27 January 2009) [3].We studied the effect of glucose variability on the main neurological endpoint of the DCCT, i.e. confirmed clinical neuropathy, and on the DCCT-defined secondary endpoints separately: clinical neuropathy, abnormal nerve conduction studies, and abnormal autonomic function [4].In addition, we determined its effect on the subvariables median motor F-wave latency, sural amplitude, sensory signs and beat-tobeat heart-rate variation (with Valsalva ratio <1.5), as these variables tend to be the first affected by diabetes.We included only data from baseline to 4 years (autonomic function data) or 5 years of follow-up in the analyses as more than 50% of the patients did not have records of glucose data after 5 years of follow-up.We assessed glycaemic variables from seven-point blood glucose profiles collected every 3 months.We included all glucose profiles with five observations or more during the 24 h period, extrapolating missing values from the surrounding points [5].Mean blood glucose was calculated by the AUC using the trapezoidal rule [6].Variability of blood glucose (within-day SD) was calculated as the SD of daily blood glucose around the mean from each quarterly visit and the mean amplitude of glycaemic excursions (MAGE) [7].Last, we calculated the mean SD from individual glucose data transformed to a symmetric distribution according to Kovatchev [8].Glucose variability from baseline to 4 or 5 years was assessed as the mean SD and mean MAGE from the first quarter to the 16th or 20th quarter of follow-up, respectively.The main characteristics of the patients in the group analysed for confirmed clinical neuropathy are listed in Table 1.Of the 1,441 patients in total, 1,160 were included in this specific analysis.Ninety-two patients were excluded from the analysis because they had a positive score at baseline and 189 patients had missing data on confirmed clinical neuropathy at baseline (n=3) or at 5 years (n=186).