Skin collagen fluorophore LW-1 versus skin fluorescence as markers for the long-term progression of subclinical macrovascular disease in type 1 diabetes

Cardiovasc Diabetol. 2016 Feb 11;15:30. doi: 10.1186/s12933-016-0343-3.


Background: Skin collagen Long Wavelength Fluorescence (LWF) is widely used as a surrogate marker for accumulation of advanced glycation end-products. Here we determined the relationship of LWF with glycemia, skin fluorescence, and the progression of complications during EDIC in 216 participants from the DCCT.

Methods: LW-1 and collagen-linked fluorescence (CLF) were measured by either High Performance Liquid Chromatography (HPLC) with fluorescence detection (LW-1) or total fluorescence of collagenase digests (CLF) in insoluble skin collagen extracted from skin biopsies obtained at the end of the DCCT (1993). Skin intrinsic fluorescence (SIF) was noninvasively measured on volar forearm skin at EDIC year 16 by the SCOUT DS instrument.

Results: LW-1 levels significantly increased with age and diabetes duration (P < 0.0001) and significantly decreased by intensive vs. conventional glycemic therapy in both the primary (P < 0.0001) and secondary (P < 0.037) DCCT cohorts. Levels were associated with 13-16 year progression risk of retinopathy (>3 sustained microaneurysms, P = 0.0004) and albumin excretion rate (P = 0.0038), the latter despite adjustment for HbA1c. Comparative analysis for all three fluorescent measures for future risk of subclinical macrovascular disease revealed the following significant (P < 0.05) associations after adjusting for age, diabetes duration and HbA1c: coronary artery calcium with SIF and CLF; intima-media thickness with SIF and LW-1; and left ventricular mass with LW-1 and CLF.

Conclusions: LW-1 is a novel risk marker that is robustly and independently associated with the future progression of microvascular disease, intima-media thickness and left ventricular mass in type 1 diabetes. Trial registration NCT00360815 and NCT00360893 at

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Biomarkers / metabolism
  • Biopsy
  • Carotid Artery Diseases / diagnosis
  • Carotid Artery Diseases / etiology*
  • Carotid Artery Diseases / metabolism
  • Chromatography, High Pressure Liquid
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / metabolism
  • DNA-Binding Proteins / metabolism*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetic Angiopathies / diagnosis
  • Diabetic Angiopathies / etiology*
  • Diabetic Angiopathies / metabolism
  • Diabetic Cardiomyopathies / diagnosis
  • Diabetic Cardiomyopathies / etiology
  • Diabetic Cardiomyopathies / metabolism
  • Disease Progression
  • Fluorometry
  • Forearm
  • Glycation End Products, Advanced / metabolism*
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Hypertrophy, Left Ventricular / diagnosis
  • Hypertrophy, Left Ventricular / etiology*
  • Hypertrophy, Left Ventricular / metabolism
  • Hypoglycemic Agents / therapeutic use
  • Luminescent Measurements
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Skin / drug effects
  • Skin / metabolism*
  • Tandem Mass Spectrometry
  • Time Factors


  • Biomarkers
  • DNA-Binding Proteins
  • Glycation End Products, Advanced
  • HSFX1 protein, human
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Hypoglycemic Agents

Associated data