title: Autonomic nerve testing predicts the development of complications: a 12-year follow-up study.
abstract: OBJECTIVE
  Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests.
  
  
  METHODS
  From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0-16.8], duration of diabetes 6.3 years [4.0-9.6], and A1C 8.3% [7.5-9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35).
  
  
  RESULTS
  At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P = 0.016) and retinopathy (4.83 [1.3-17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later.
  
  
  CONCLUSIONS
  In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Locked Bag 4001, Sydney, NSW 2145, Australia. annm4@chw.edu.au
authors.forename: Ann M
authors.initials: AM
authors.lastname: Maguire
authors.forename: Maria E
authors.initials: ME
authors.lastname: Craig
authors.forename: Anne
authors.initials: A
authors.lastname: Craighead
authors.forename: Albert K F
authors.initials: AK
authors.lastname: Chan
authors.forename: Janine M
authors.initials: JM
authors.lastname: Cusumano
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Hing
authors.forename: Martin
authors.initials: M
authors.lastname: Silink
authors.forename: Neville J
authors.initials: NJ
authors.lastname: Howard
authors.forename: Kim C
authors.initials: KC
authors.lastname: Donaghue
mesh_terms: D000293:Adolescent; D000419:Albuminuria / Q000453:epidemiology; D001341:Autonomic Nervous System / Q000503:physiopathology*; D001794:Blood Pressure; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000453:epidemiology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D011680:Pupil / Q000502:physiology; D012307:Risk Factors; D013997:Time Factors