Aims: The LDIFLARE method has been previously shown to be a sensitive measure of small fibre function. In this longitudinal 5-year study, we evaluated the LDIFLARE as a method to predict the development of DPN.

Methods: From the cohort of 160 people with type 1 and 2 diabetes recruited at baseline, 58 patients who did not have DPN at onset and completed 5 years of follow up were studied. Incident DPN was defined as progression to a Neurology Disability Sore (NDS) of ≥3. All subjects underwent comprehensive neurological review including electrophysiology. We used duration-dependent receiver operating characteristic (ROC) curves to calculate the predictive validity of the baseline LDIFLARE for the development of a NDS of ≥3.

Results: Of the 58 subjects without DPS who completed 5yr follow up, 34 had Type-1 and 24 had Type-2 diabetes; 35 females. Mean age (±SD) was 47.1±8.8 years. Mean follow up time was 5.4 years. Of these, 24 (T1Dm & 14 T2DM) progressed to a NDS of ≥3 (41%; 7.7 events per 100 subject-years) . There was a strong correlation with older age, longer duration of diabetes, raised HbA1c and raised triglycerides (significance: p<0.05) but no effect of BMI or blood pressure. The linear rate of fall of LDIFLARE from baseline in newly diagnosed DPN was 0.16 cm2/yr for T1DM and 0.22cm2/yr for T2DM. The area under the ROC curve for LDIFLARE ranged between 0.66 and 0.75. The optimal diagnostic threshold for a baseline LDIFLARE of 5.05cm2 was associated with 71% sensitivity, 74% specificity, and a hazard ratio of 3.73 (95% CI 2.14-6.73; P < 0.01) for new-onset DPN.

Conclusions: We conclude that the LDIFLARE method with a cut-off of 5.cm2 showed good predictive validity for identifying people with diabetes who are at risk of developing DPN. We suggest that as a measure of small fibre function, the LDIFLARE method may be preferred over conventional large fibre methods in predicting the later development of clinical DPN.


S.Sharma: None. J.Cross: None. G.Rayman: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at