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

Abstract

OBJECTIVETo 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 METHODSSIF 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).RESULTSThe 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 operating 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.CONCLUSIONSSIF, 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.

Relationship Between Skin Intrinsic Fluorescence—an Indicator of Advanced Glycation End Products—and Upper Extremity Impairments in Individuals With Diabetes Mellitus

“…This method uses near ultraviolet and blue light to excite and measure the fluorescence produced by AGEs. [25][26][27] Estimating AGE levels in the skin is particularly beneficial because AGEs that accumulate in the skin have an estimated half-life of 15-20 years, and therefore, are a good indicator of long-term glycemic exposure of collagen-rich tissues. 28,29 Previous research has shown that this SIF measure is correlated with the severity of tissuespecific diabetes related complications such as peripheral neuropathy (seen mainly in the distal lower extremities), increased arterial stiffness, and nephropathy.…”

Cross-Sectional Evaluation of Noninvasively Detected Skin Intrinsic Fluorescence and Mean Hemoglobin A1c in Type 1 Diabetes

“…In a prospective study of patients with well-controlled type 2 diabetes, after a mean follow-up of 3.1 years, patients with a higher baseline skin fluorescence reading had a higher likelihood of developing microalbuminuria or neuropathy, but again not retinopathy. 7 Conway et al 9 demonstrated that SIF was even more strongly associated with the presence of autonomic neuropathy and confirmed distal symmetrical polyneuropathy than mean HbA1c. There also appears to be an association between skin fluorescence and risk of macrovascular complications.…”

“…Participants from the University of Pittsburgh were included from the longitudinal observational Pittsburgh Epidemiology of Diabetes Complications (EDC) cohort, 8,9 where skin fluorescence was assessed in their 20 th year of follow-up, 2 years after routine clinical and laboratory assessment, and participants from MHRI were recruited and enrolled from patients receiving their diabetes care from MHRI's investigator (R.E.R.) or immediate colleagues.…”

“…As in previous reports regarding associations of SIF with neuropathy and coronary artery disease in this cohort, k x was set to 0.9, k m was set to 0.0, and the resulting intrinsic fluorescence, f xm , was integrated over the 441-482-nm spectral region to give the SIF (in arbitrary units). 9,13 The Hoorn coefficient of variation of SIF, quantifying the intrasubject variance, was previously reported at 4%. 14 …”

“…The skin reflectance was measured over both the excitation and emission regions and was used to compensate for absorbance caused by melanin and hemoglobin. 9,12 The intrinsic fluorescence correction is expressed in Eq. 1:…”