Decline in neurophysiological function after 7 years in an adolescent diabetic cohort and the role of aldose reductase gene polymorphisms.
OBJECTIVE
This 7-year longitudinal study examines the potential impact of aldose reductase gene (AKR1B1) polymorphisms on the decline of nerve function in an adolescent diabetic cohort.


METHODS
Patients with type 1 diabetes (n = 262) were assessed with three cardiovascular autonomic tests (heart rate variation during deep breathing, Valsalva maneuver, and during standing from a lying position) and pupillometry (resting pupil diameter, constriction velocity, and reflex amplitude), thermal, and vibration thresholds on the foot. Genotyping was performed for promoters (C-106T and C-12G), (CA)(n) dinucleotide repeats, and intragenic BamH1 polymorphism.


RESULTS
Median time between first and last assessment was 7.0 years (interquartile range 5.1-11.1), with a median of five assessments (four to seven) per individual. At first assessment, median age was 12.7 years (11.7-13.9), median duration was 5.3 years (3.4-8.0), and median HbA(1c) was 8.5% (7.8-9.3). All tests declined over time except for two cardiovascular autonomic tests and vibration discrimination. Faster decline in maximum constriction velocity was found to associate with the Z-2 allele (P = 0.045), Z-2/Z-2 (P = 0.026). Slower decline in hot thermal threshold discrimination associated with Z+2 (P = 0.044), Z+2/Z+2 (P < 0.0005), Z+2/T (P = 0.038), and bb (P = 0.0001).


CONCLUSIONS
Most autonomic and quantitative sensory nerve testings declined over time. AKR1B1 polymorphisms were strongly associated with the rate of decline of these complications.
Thamotharampillai
Keerthi
K
Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
Chan
Albert K F
AK
Bennetts
Bruce
B
Craig
Maria E
ME
Cusumano
Janine
J
Silink
Martin
M
Oates
Peter J
PJ
Donaghue
Kim C
KC
D000293:Adolescent; D000449:Aldehyde Reductase / Q000235:genetics*; D000483:Alleles; D001341:Autonomic Nervous System / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D018900:Dinucleotide Repeats / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D012025:Reflex, Pupillary / Q000502:physiology; D014636:Valsalva Maneuver / Q000502:physiology
D000449:Aldehyde Reductase