Measurement of Cooling Detection Thresholds for Identification of Diabetic Sensorimotor Polyneuropathy in Type 1 Diabetes

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. RESEARCH DESIGN AND 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 (LDI(FLARE)). 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). AUC(CDT) was 0.863 which was similar to AUC(TCNS) (0.858, p = 0.24) and AUC(HRV) (0.788, p = 0.05), but exceeded AUC(LDIFLARE) (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.