title: Measurement of cooling detection thresholds for identification of diabetic sensorimotor polyneuropathy in type 1 diabetes.
abstract: OBJECTIVE
  Compared to recently-studied novel morphological measures, conventional small nerve fiber functional tests have not been systematically studied for identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine and compare the diagnostic performance of cooling detection thresholds (CDT) in a cross-sectional type 1 diabetes cohort.
  
  
  METHODS
  136 subjects with type 1 diabetes and 52 healthy volunteers underwent clinical and electrophysiological examination for DSP classification concomitantly with the Toronto Clinical Neuropathy Score (TCNS) and three small fiber function tests: CDT, heart rate variability (HRV), and laser doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE). Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves in the type 1 diabetes cohort.
  
  
  RESULTS
  Type 1 diabetes subjects were 42±17 years of age with mean HbA1c 7.9±1.7%. Fifty-nine (45%) met the case definition for DSP. CDT values were lowest in cases with DSP (18.3±8.4°C) compared to controls without DSP (28.4±3.5°C) and to healthy volunteers (29.6±1.8°C; p-value for both comparisons<0.0001). AUCCDT was 0.863 which was similar to AUCTCNS (0.858, p = 0.24) and AUCHRV (0.788, p = 0.05), but exceeded AUCLDIFLARE (0.750, p = 0.001). The threshold of <25.1°C was equivalent to the lower bound of the healthy volunteer 95% distribution [25.1, 30.8°C] and performed with 83% sensitivity and 82% specificity.
  
  
  CONCLUSIONS
  Akin to novel small fiber morphological measures, CDT is a functional test that identifies DSP with very good diagnostic performance. These findings support further research that revisits the role of CDT in early DSP detection.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Lysy
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Leif E
authors.initials: LE
authors.lastname: Lovblom
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Halpern
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mylan
authors.initials: M
authors.lastname: Ngo
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ng
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrej
authors.initials: A
authors.lastname: Orszag
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ari
authors.initials: A
authors.lastname: Breiner
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Bril
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Perkins
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D012372:ROC Curve; D066191:Sensorimotor Cortex / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000502:physiology*