Background: The worldwide prevalence of diabetic foot ulcers (DFUs) among persons with diabetes is estimated at 6.3%, with an annual incidence of 9.1 to 26.1 million persons. The early detection of asymmetrical plantar temperature elevation, followed by reduction of weight -bearing on the affected foot, may be an effective mode of prevention.
Methods: Patients with diabetes and peripheral neuropathy (DFU risk groups 2/3) were monitored for plantar abnormalities with a telemedical system consisting of sole inserts with temperature sensors and photographic documentation. An open, prospective, randomized controlled trial was performed to determine whether this system prevented DFUs. The intervention and control groups were also trained in ulcer prevention and observed in follow-up at 6-month intervals for 24 months.
Results: 283 patients were recruited. In 85 137 observation days, DFUs arose in five patients in the control group (n = 143) and in no patient in the intervention group (n = 140). The primary outcome measure was the hazard ratio, which was calculated to be 0.015 (95% confidence interval [0; 19,717]; p = 0.25) after adjustment for age, sex, severity of neuropathy, and risk class. There were 239 alarms and 75 instructions to reduce weight-bearing on the foot. The subjects carried out the telemedical application on about 70% of the days of observation. Quality of life improved in both groups.
Conclusion: The tele-health system used in this trial is practical and enables the early detection of morbidity. Likely explanations for the unexpectedly low ulceration rate in this trial (and, in turn, for the lack of statistical significance) include the availability of a training program and regular follow-up examinations to patients in both arms of the trial, along with lower mobility levels due to the COVID pandemic.
Original article
Diabetic foot ulcer (DFU) is the most commonly occurring complication of diabetes. It carries a risk of amputation of the lower extremity with associated high morbidity and mortality (
In 80% of cases DFU is accompanied by peripheral polyneuropathy, resulting in defective sensation of pain and temperature (
In our RCT, a telehealth application was set up with twice daily home recordings of plantar temperatures by means of sensor-equipped insoles and photodocumentation of foot abnormalities using cell phones. The study evaluated the effectiveness of the established telehealth system with close exchange of health data in preventing the onset of diabetic foot syndrome and improving patient compliance and quality of life in a domestic setting.
Study design
This open-label, prospective, randomized clinical trial (German Clinical Trials Registry DRKS00013798) was designed for patients with diabetes and at risk for DFU due to the presence of intermediate to severe peripheral neuropathy. The study protocol was approved by the local ethics committee on 8 January 2018 and the complete study protocol has been published (
In addition to the training session, probands in the intervention group were provided with sensor-equipped insoles manufactured by Thorsis Technologies GmbH and a cellphone app programed at the Department of Nephrology and Hypertension, Diabetes, and Endocrinology that exchanged data via the IQ-Trial Study Server with the physicians in the clinic (Figure 1). Plantar foot temperature recordings were recommended twice daily at an interval of > 4 hours (each lasting ~ 5 minutes). The preset alarm algorithm automatically notified the study physician via the dashboard when temperature asymmetries (> 1.5 °C) between corresponding sensor sites exceeded 32 hours (eFigure 1). The study participants were instructed to use the app to perform foot inspections, provide foot status reports, and upload foot photographs. The study physician decided on the basis of all available data whether or not to recommend a 5-day intervention period of foot offloading. On-site visits were arranged if temperature asymmetries persisted.
All patients were instructed to consult their study physician immediately if the recommended daily self -inspection revealed signs of inflammation (e.g., redness, pain, and sores), foot abnormalities, or ulceration. Regular study visits were planned every 6 months. These measures represent a very high standard of care. A detailed explanation of interventions is provided in the eSupplement.
The primary outcome of this study was the time to onset of the first foot ulcer (= Wagner grade 1), classified according to the Wagner/Armstrong criteria (
The secondary outcomes were:
* Adherence to daily temperature measurements
* Frequency of temperature alarms and intervention instructions
* Temperature drops correlating with limb ischemia
* Number of adverse events (AEs) and severe adverse events (SAEs)
* Quality of life (QOL) based on the World Health Organization-5 score
* Precursors of DFU: redness, infections, or wounds on the foot
From January 2018 to February 2020, 351 patients with diabetes and peripheral polyneuropathy were recruited (Figure 2). Of these patients, 283 consented to the study protocol and were randomized to either the control or the intervention group in a ratio of 1:1. Six patients from the control group and seven from the intervention group were excluded from the intention-to-treat (ITT) analyses ("modified protocol") because they withdrew their consent before the training session due to either the complexity of the study protocol or dissatisfaction with their group allocation (n = 13). The baseline characteristics of the patients (n = 270) were similar in the two groups (Table, eTable 1). The study closed on 20 March 2021. A total of 85 137 observation days for the control group and 83 312 observation days for the intervention group were included in the modified ITT analysis.
Five patients developed foot ulcers in the control group versus no patients in the intervention group (classified according to the Wagner/Armstrong criteria as four DFU grade 1 stage A and one grade 1 stage B) (
The plantar temperature recordings were "normalized" by subtraction of ambient temperature recordings from the same insole by an additional sensor integrated in the Bluetooth device. The predefined algorithm calculated asymmetries of temperatures recorded by sensors from both insoles and indicated on the dashboard when the alarm level was = 3 (eFigure 1). The study physicians assessed the plausibility of these findings on the basis of all available information. In 75 cases of verified alarms, instructions on the 5-day foot offloading intervention were initiated by the physician (eFigure 2). In cases of misclassification due to technical defects (missing or faulty sensor data), absent contact of the plantar foot with the hallux sensor, or temperature decrease (possibly due to intermittent limb ischemia), the alarm levels were reset.
The overall adherence rate was defined as measurement days divided by observation days. This rate was calculated at 70% (eFigure 3). The numbers of AEs and SAEs recorded within the study did not differ between the two groups (eTable 3). The QOL of both groups increased during the study period (eTable 4). After 24 months, QOL was slightly better in patients with the telehealth app.
According to the post hoc analyses, patients with advanced neuropathy had shorter time-to-alarm periods than those with minor neuropathy (log-rank test, p = 0.048, Figure 3b). Overall, 239 alarms within the 83 312 observation days of the intervention group were identified post hoc by means of manual supervised classification by two physicians (Figure 3c, d). In 33 of 40 inflammation-related alarms, foot offloading was performed as instructed (eTable 5). Figure 4 presents examples of plantar foot temperature asymmetry due to intermittent ischemia.
Telehealth technology applications may aid medical professionals in their interaction with patients and may also help patients with chronic diseases to monitor their health status (
The first reports on the utility of plantar temperature recordings for early detection of tissue damage and incipient DFU formation were published more than 15 years ago, and several small to medium-sized clinical trials have described positive results (
The number of alarms triggered by the predefined algorithm was unexpectedly high. The caring study physician evaluated all data on a daily basis and compared the plantar temperature recordings with those of the preceding weeks and with the ambient temperature before recommending foot offloading. By this means, transient ischemia could be distinguished from asymmetric inflammation in most cases. The main cause of alarms related to transient episodes of ischemia, not to inflammatory events with asymmetric plantar and ambient temperature values. Furthermore, comparison with historical values indicated a downshift of temperatures in these patients. Individual cases with infrared imaging confirmed these findings. Thus, temperature decreases possibly indicating ischemic events are highly prevalent (
Do the Smart Prevent Diabetic Feet study results indicate more efficient delivery of care for patients? The Cox regression analysis of our data reveals no statistically significant benefit of the telemedicine intervention. Nevertheless, the estimated effect is clearly in the direction of reduced risk for DFU. Because of the small number of cases, however, the confidence interval is very wide. An advantage of the telehealth approach is the implementation of a surveillance strategy that it allows information to be gathered without organizational obstacles (e.g., consulting hours, on-site physician visits, travel). During the study, a learning curve in patient care by telehealth was accompanied by expanding functionality of the dashboard, allowing the physicians to interact with the participants via messages, short notices, standardized questionnaires and foot photographs. Furthermore the availability of temperature recordings from the preceding days and weeks permitted the physicians to detect changes over time and swiftly to differentiate between increases and decreases in temperature. The user-centered design facilitates the integration of sensor data with foot findings from the pictorial material. In this way, medical interpretation and evaluation could be integrated into clinical assessment into workflows and clinical routines (
One drawback of the study is the unblinded nature of the temperature measurement for patients, physicians, and biostatisticians. In view of the uncertainties that would arise from false reporting of temperatures or the lack of intervention in the case of asymmetric temperature elevation, both mock insole recording and measurement without intervention recommendations from the study center seemed unrealistic. On the other hand, ulcer diagnosis in the presence of skin lesions is an objective finding with low likelihood of bias. The assessment and classification of ulcers was confirmed by performance of clinical examinations by two independent examiners. The time investment of the dashboard supervising physician was not recorded systematically, so no objective number can be given. It is noteworthy that functionality improved considerably and that color coding of the preset alarm levels facilitated an immediate overview of patient status. Since the number of primary events (DFU) was much lower than expected, the results should be confirmed in another study.
In summary, this study provides the first experience of telehealth interactions between physicians and patients over an extended period in persons with diabetes and polyneuropathy. The dashboard facilitated data interpretation and the diagnosis of comorbidities by virtue of the combination of digital images and temperature recordings. The adherence rates and the QOL indicated acceptance of this approach by the majority of the mostly elderly participants, which is regarded as a basic requirement for implementation (
We would like to thank Ingeborg Bloos-Walzer, Marie Theres Sarji, Andre Pfannkuche, and Fred Samland (Thorsis GmbH) for their support in the early stages of the study. The statistical analyses were planned and performed by the study team, Mrs. Anke Lux and Prof. Dr. Siegfried Kropf of the Institute for Biometry and Medical Informatics, Otto -von-Guericke University, Magdeburg. We dedicate this study to Thorsten Szczepanski of Thorsis Technologies GmbH, who inspired us all with his enthusiasm and his commitment to improving patient care.
The European Fund for Regional Development and the Ministry of Science, Economics and Digitalization of the State of Saxony-Anhalt funded this project under the Autonomy in Old Age Program (project nos. ZS/2016/05/78615, ZS/2018/12/95325). AM was funded by the China Scholarship Council (CSC no. 201508120093).
We are open to any reasonable requests for the original data directed to the corresponding author, provided the requested data relates to the data published in the article and do not compromise any future publication or any other related issues. These data may include anonymous data from the sensor measurements and statistical analyses. The data will be available for at least 10 years from the date of publication.
PRM has filed a patent on temperature measurement for early detection of diabetic foot ulcers. Together with Thorsten Szczepanski he has founded the company Medixmind GmbH to optimize the analyses of the sensor data, which were transferred in double-pseudonymized manner to a server. The technical staff of Medixmind and of Thorsis GmbH had access to the pseudonymized data sets. Furthermore, PRM has received personal fees from Berlin-Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Novo Nordisk, and Novartis for consultation as well as fees for presentations and memberships in advisory boards.
The remaining authors declare that no conflict of interest exists.
Manuscript received on 20 March 2023, revised version accepted on 18 October 2023
By A. Ming; A. Alhajjar; I. Walter; C. Piehler; J. Hoetzsch; M. Leuckert; V. Clemens; A. Petrow; I. M. Siddiquee; F. G. Scurt; B. Isermann and P. R. Mertens
Corresponding author Prof. Dr. med. Peter R. Mertens Universitätsklinik für Nieren- und Hochdruckkrankheiten, Diabetologie und Endokrinologie, Otto-von-Guericke -Universität Magdeburg Leipziger Str. 44, 39120 Magdeburg, Germany peter.mertens@med.ovgu.de