Skin Intrinsic Fluorescence Correlates With Autonomic and Distal Symmetrical Polyneuropathy in Individuals With Type 1 Diabetes

  1. Trevor J. Orchard, MD, MMedSci4
  1. 1Division of Epidemiology, Vanderbilt University, Nashville, Tennessee
  2. 2Department of Endocrinology, Diabetes, and Metabolism, MedStar Health Research Institute, Hyattsville, Maryland
  3. 3Department of Research, Development, and Engineering, VeraLight, Albuquerque, New Mexico
  4. 4Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
  1. Corresponding author: Trevor J. Orchard, orchardt{at}


OBJECTIVE To determine whether skin intrinsic fluorescence (SIF) was associated with autonomic neuropathy and confirmed distal symmetrical polyneuropathy (CDSP) in 111 individuals with type 1 diabetes (mean age 49 years, mean diabetes duration 40 years).

RESEARCH DESIGN AND METHODS SIF was measured using the SCOUT DM device. Autonomic neuropathy was defined as an electrocardiographic abnormal heart rate response to deep breathing (expiration-to-inspiration ratio <1.1). CDSP was defined using the Diabetes Control and Complications Trial clinical exam protocol (the presence of two or more of the following: symptoms, sensory and/or motor signs and/or reduced/absent tendon reflexes consistent with DSP) confirmed by the presence of an abnormal age-specific vibratory threshold (using a Vibratron II tester).

RESULTS The prevalence of autonomic neuropathy and CDSP were 61 and 66%, respectively. SIF was higher in those with autonomic neuropathy (P < 0.0001). In multivariable analyses controlling for age and updated mean (18-year average) HbA1c, and allowing for other univariately and clinically significant correlates of autonomic neuropathy, each SD change in SIF was associated with a 2.6-greater likelihood of autonomic neuropathy (P = 0.006). Receiver-operator characteristic (ROC) analyses revealed that SIF and updated mean HbA1c accounted for 80 and 57%, respectively, of the area under the curve (AUC) for autonomic neuropathy. SIF also was higher in those with CDSP (P < 0.0001) and remained so in multivariable analyses (odds ratio 2.70; P = 0.005). ROC analyses revealed that SIF and updated mean HbA1c accounted for 78 and 59%, respectively, of the AUC for CDSP.

CONCLUSIONS SIF, a marker of dermal advanced glycation end products, appears to be more strongly associated with the presence of both CDSP and autonomic neuropathy than mean HbA1c.

  • Received September 16, 2010.
  • Accepted January 8, 2011.

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