Endoneurial Capillary Abnormalities Presage Deterioration of Glucose Tolerance and Accompany Peripheral Neuropathy in Man

Endoneurial Capillary Abnormalities Presage Deterioration of Glucose Tolerance and Accompany Peripheral Neuropathy in Man Soley Thrainsdottir 1 , Rayez A. Malik 2 , Lars B. Dahlin 3 , Peter Wiksell 4 , Karl F. Eriksson 5 , Ingmar Rosén 6 , Jesper Petersson 1 , Douglas A. Greene 7 and Göran Sundkvist 4 1 Department of Neurology, University of Lund, Malmö University Hospital, Malmö, Sweden 2 Academic Department of Medicine, Royal Infirmary, Manchester, U.K 3 Department of Hand Surgery, University of Lund, Malmö University Hospital, Malmö, Sweden 4 Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden 5 Department of Vascular Diseases, University of Lund, Malmö University Hospital, Malmö, Sweden 6 Department of Clinical Neurophysiology, University of Lund, Malmö University Hospital, Malmö, Sweden 7 Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan Address correspondence and reprint requests to Professor Göran Sundkvist, MD, Department of Endocrinology, Malmö University Hospital, SE 205 02 Malmö, Sweden. E-mail: goran.sundkvist{at}endo.mas.lu.se Abstract To explore whether microangiopathy is associated with disturbed glucose tolerance and peripheral neuropathy, we assessed endoneurial capillary morphology in sural nerve biopsies from men with diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Baseline morphology was related to glucose tolerance and neuropathy at baseline and at follow-up 6 years later. Capillary density (in number per millimeters squared) at baseline was higher in subjects with diabetes ( n = 10) compared with those with NGT ( n = 5) at follow-up (median [interquartile range]) (86.0 [24.3] vs. 54.9 [17.1]; P = 0.0200) and in those progressing from IGT to diabetes ( n = 4) compared with those with persistent IGT ( n = 4) (86.7 [25.2] vs. 54.1 [14.6]; P = 0.0433). The capillary luminal area (in micrometers squared) was lower in subjects with NGT progressing to IGT ( n = 2) or subjects with IGT progressing to diabetes ( n = 3) compared with subjects with constant NGT ( n = 6) or constant IGT ( n = 4) (11.9 [2.4] vs. 20.8 [7.8]; P = 0.0201). The capillary basement membrane area (in micrometers squared) was increased in patients with peripheral neuropathy ( n = 10) compared with those without ( n = 7) (114.6 [68.8] vs. 75.3 [28.7]; P = 0.0084). In conclusion, increased capillary density was associated with current or future diabetes, decreased capillary lumi