Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Diabetes Care 29:2053-2057, 2006
DOI: 10.2337/dc06-0678
© 2006 by the American Diabetes Association
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thamotharampillai, K.
Right arrow Articles by Donaghue, K. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thamotharampillai, K.
Right arrow Articles by Donaghue, K. C.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Pathophysiology/Complications
Original Article

Decline in Neurophysiological Function After 7 Years in an Adolescent Diabetic Cohort and the Role of Aldose Reductase Gene Polymorphisms

Keerthi Thamotharampillai, GMEDSC1, Albert K.F. Chan, MAPPSTAT1, Bruce Bennetts, PHD2,3, Maria E. Craig, PHD1,3,4, Janine Cusumano1, Martin Silink, MD1,3, Peter J. Oates, PHD5 and Kim C. Donaghue, PHD1,3

1 Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Westmead, NSW, Australia
2 Department of Molecular Genetics, The Children’s Hospital at Westmead, Westmead, NSW, Australia
3 University of Sydney, Sydney, NSW, Australia
4 University of NSW School of Women’s and Children’s Health, Sydney, NSW, Australia
5 Pfizer Global Research and Development, Groton, Connecticut

Address correspondence and reprint requests to Prof. Kim C. Donaghue, Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia. E-mail: kimd{at}chw.edu.au

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.

RESEARCH DESIGN AND 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 HbA1c 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.

Abbreviations: DBHRV, heart rate variation during deep breathing


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2006 by the American Diabetes Association.