title: Validation of cooling detection threshold as a marker of sensorimotor polyneuropathy in type 2 diabetes.
abstract: OBJECTIVE
  We aimed to validate the performance cooling detection thresholds (CDT) to detect diabetic sensorimotor polyneuropathy (DSP) in type 2 diabetes.
  
  
  METHODS
  Two hundred and twenty participants with type 2 diabetes underwent clinical and electrophysiological examinations including 3 small fiber function tests: CDT, heart rate variability (HRV) and LDIFLARE. Clinical DSP was defined by consensus criteria whereas preclinical DSP was defined by presence of at least one electrophysiological abnormality. Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic curves.
  
  
  RESULTS
  Participants were aged 63 ± 11 years with mean HbA1c of 7.5 ± 1.6%. The 139 (63%) clinical DSP cases had mean CDT values of 18.3 ± 8.9°C; the 52 (24%) preclinical DSP cases had 25.3 ± 3.5°C; and the 29 (13%) controls had 27.1 ± 3.8°C; (p-value<0.02 for all comparisons). For identification of clinical DSP cases, AUCCDT was 0.79 which exceeded AUCHRV (0.60, p=<0.0001) and AUCLDI FLARE (0.69, p=0.0003), optimal threshold <22.8°C (64% sensitivity, 83% specificity). Preclinical DSP AUCCDT was 0.80, also exceeding the other 2 measures (p<0.02 for both comparisons), optimal threshold ≤27.5°C (83% sensitivity, 72% specificity).
  
  
  CONCLUSIONS
  CDT had good diagnostic performance for identification of both clinical and preclinical neuropathy in type 2 diabetes. Its use as a non-invasive screening tool should be considered for research and clinical practice.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Farooqi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada.
authors.forename: Leif E
authors.initials: LE
authors.lastname: Lovblom
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Lysy
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada.
authors.forename: Ilia
authors.initials: I
authors.lastname: Ostrovski
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Halpern
authors.affiliation: Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Mylan
authors.initials: M
authors.lastname: Ngo
authors.affiliation: Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ng
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada.
authors.forename: Andrej
authors.initials: A
authors.lastname: Orszag
authors.affiliation: Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Ari
authors.initials: A
authors.lastname: Breiner
authors.affiliation: Ellen and Martin Prosserman Centre for Neuromuscular Diseases, Division of Neurology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Bril
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, ON, Canada. Electronic address: BPerkins@mtsinai.on.ca.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Perkins
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D015415:Biomarkers; D015331:Cohort Studies; D003080:Cold Temperature; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003929:Diabetic Neuropathies / Q000175:diagnosis*; D042241:Early Diagnosis; D006442:Glycated Hemoglobin / Q000032:analysis; D006769:Hospitals, General; D006786:Hospitals, Urban; D006801:Humans; D008875:Middle Aged; D009864:Ontario; D010044:Outpatient Clinics, Hospital; D011115:Polyneuropathies / Q000150:complications / Q000175:diagnosis*; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012684:Sensory Thresholds
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Cooling detection threshold; Diabetic neuropathy; Diagnostic tests; Quantitative sensory testing; Type 2 diabetes