Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort Study

Abstract BackgroundDiabetes-related lower extremity complications, such as foot ulceration and amputation, are on the rise, currently affecting nearly 131 million people worldwide. Methods for early detection of individuals at high risk remain elusive. While data-driven diabet...

Full description

Saved in:
Bibliographic Details
Main Authors: Alyce S Adams, Catherine Lee, Gabriel Escobar, Elizabeth A Bayliss, Brian Callaghan, Michael Horberg, Julie A Schmittdiel, Connie Trinacty, Lisa K Gilliam, Eileen Kim, Nima S Hejazi, Lin Ma, Romain Neugebauer
Format: Article
Language:English
Published: JMIR Publications 2025-05-01
Series:JMIR Diabetes
Online Access:https://diabetes.jmir.org/2025/1/e60141
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849472232172027904
author Alyce S Adams
Catherine Lee
Gabriel Escobar
Elizabeth A Bayliss
Brian Callaghan
Michael Horberg
Julie A Schmittdiel
Connie Trinacty
Lisa K Gilliam
Eileen Kim
Nima S Hejazi
Lin Ma
Romain Neugebauer
author_facet Alyce S Adams
Catherine Lee
Gabriel Escobar
Elizabeth A Bayliss
Brian Callaghan
Michael Horberg
Julie A Schmittdiel
Connie Trinacty
Lisa K Gilliam
Eileen Kim
Nima S Hejazi
Lin Ma
Romain Neugebauer
author_sort Alyce S Adams
collection DOAJ
description Abstract BackgroundDiabetes-related lower extremity complications, such as foot ulceration and amputation, are on the rise, currently affecting nearly 131 million people worldwide. Methods for early detection of individuals at high risk remain elusive. While data-driven diabetic polyneuropathy algorithms exist, high-performing, clinically useful tools to assess risk are needed to improve clinical care. ObjectiveThis study aimed to develop an electronic medical record–based machine learning algorithm that would predict lower extremity complications. MethodsWe conducted a retrospective longitudinal cohort study to predict the risk of lower extremity complications within 24 months of an initial diagnosis of diabetic polyneuropathy. From an initial cohort of 468,162 individuals with at least 1 diagnosis of diabetic polyneuropathy at one of 2 multispecialty health care systems (based in northern California and Colorado) between April 2012 and December 2016, we created an analytic cohort of 48,209 adults with continuous enrollment, who were newly diagnosed with no evidence of end-of-life care. The outcome was any lower extremity complication, including foot ulceration, osteomyelitis, gangrene, or lower extremity amputation. We randomly split the data into training (38,569/48209; 80%) and testing (9,640/48209; 20%) datasets. In the training dataset, we used super Learner (SL), an ensemble learning method that employs cross-validation and combines multiple candidate risk predictors, into a single risk predictor. We evaluated the performance of the SL risk predictor in the testing dataset using the receiver operating characteristic curve and a calibration plot. ResultsOf the 48,209 individuals in the cohort, 2327 developed a lower extremity complication during follow-up. The SL risk estimator exhibited good discrimination (AUC=0.845, 95% CI 0.826-0.863) and calibration. A modified version of our SL algorithm, simplified to facilitate real-world adoption, had only slightly reduced discrimination (AUC=0.817, 95%CI 0.797-0.837). The modified version slightly outperformed the naïve logistic regression model (AUC=0.804, 95% CI 0.783-0.825) in terms of precision gained relative to the frequency of alerts and number of patients that needed to be evaluated. ConclusionsWe have built a machine learning–based risk estimator with the potential to improve clinical detection of diabetic patients at high risk for lower extremity complications at the time of an initial diabetic polyneuropathy diagnosis. The algorithm exhibited good discriminant validity and calibration using only data from the electronic medical record. Additional research will be needed to identify optimal contexts and strategies for maximizing algorithmic fairness in both interpretation and deployment.
format Article
id doaj-art-006730fef7934201ab8e49e8d59a85f9
institution Kabale University
issn 2371-4379
language English
publishDate 2025-05-01
publisher JMIR Publications
record_format Article
series JMIR Diabetes
spelling doaj-art-006730fef7934201ab8e49e8d59a85f92025-08-20T03:24:36ZengJMIR PublicationsJMIR Diabetes2371-43792025-05-0110e60141e6014110.2196/60141Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort StudyAlyce S Adamshttp://orcid.org/0000-0002-0146-4996Catherine Leehttp://orcid.org/0000-0003-0008-9052Gabriel Escobarhttp://orcid.org/0000-0003-2540-3327Elizabeth A Baylisshttp://orcid.org/0000-0002-5264-0670Brian Callaghanhttp://orcid.org/0000-0002-8885-6748Michael Horberghttp://orcid.org/0000-0002-6971-7646Julie A Schmittdielhttp://orcid.org/0000-0001-8995-5345Connie Trinactyhttp://orcid.org/0000-0002-4799-1994Lisa K Gilliamhttp://orcid.org/0000-0001-7054-1409Eileen Kimhttp://orcid.org/0009-0007-5179-505XNima S Hejazihttp://orcid.org/0000-0002-7127-2789Lin Mahttp://orcid.org/0000-0002-7009-8213Romain Neugebauerhttp://orcid.org/0000-0002-6085-4564 Abstract BackgroundDiabetes-related lower extremity complications, such as foot ulceration and amputation, are on the rise, currently affecting nearly 131 million people worldwide. Methods for early detection of individuals at high risk remain elusive. While data-driven diabetic polyneuropathy algorithms exist, high-performing, clinically useful tools to assess risk are needed to improve clinical care. ObjectiveThis study aimed to develop an electronic medical record–based machine learning algorithm that would predict lower extremity complications. MethodsWe conducted a retrospective longitudinal cohort study to predict the risk of lower extremity complications within 24 months of an initial diagnosis of diabetic polyneuropathy. From an initial cohort of 468,162 individuals with at least 1 diagnosis of diabetic polyneuropathy at one of 2 multispecialty health care systems (based in northern California and Colorado) between April 2012 and December 2016, we created an analytic cohort of 48,209 adults with continuous enrollment, who were newly diagnosed with no evidence of end-of-life care. The outcome was any lower extremity complication, including foot ulceration, osteomyelitis, gangrene, or lower extremity amputation. We randomly split the data into training (38,569/48209; 80%) and testing (9,640/48209; 20%) datasets. In the training dataset, we used super Learner (SL), an ensemble learning method that employs cross-validation and combines multiple candidate risk predictors, into a single risk predictor. We evaluated the performance of the SL risk predictor in the testing dataset using the receiver operating characteristic curve and a calibration plot. ResultsOf the 48,209 individuals in the cohort, 2327 developed a lower extremity complication during follow-up. The SL risk estimator exhibited good discrimination (AUC=0.845, 95% CI 0.826-0.863) and calibration. A modified version of our SL algorithm, simplified to facilitate real-world adoption, had only slightly reduced discrimination (AUC=0.817, 95%CI 0.797-0.837). The modified version slightly outperformed the naïve logistic regression model (AUC=0.804, 95% CI 0.783-0.825) in terms of precision gained relative to the frequency of alerts and number of patients that needed to be evaluated. ConclusionsWe have built a machine learning–based risk estimator with the potential to improve clinical detection of diabetic patients at high risk for lower extremity complications at the time of an initial diabetic polyneuropathy diagnosis. The algorithm exhibited good discriminant validity and calibration using only data from the electronic medical record. Additional research will be needed to identify optimal contexts and strategies for maximizing algorithmic fairness in both interpretation and deployment.https://diabetes.jmir.org/2025/1/e60141
spellingShingle Alyce S Adams
Catherine Lee
Gabriel Escobar
Elizabeth A Bayliss
Brian Callaghan
Michael Horberg
Julie A Schmittdiel
Connie Trinacty
Lisa K Gilliam
Eileen Kim
Nima S Hejazi
Lin Ma
Romain Neugebauer
Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort Study
JMIR Diabetes
title Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort Study
title_full Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort Study
title_fullStr Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort Study
title_full_unstemmed Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort Study
title_short Estimating the Risk of Lower Extremity Complications in Adults Newly Diagnosed With Diabetic Polyneuropathy: Retrospective Cohort Study
title_sort estimating the risk of lower extremity complications in adults newly diagnosed with diabetic polyneuropathy retrospective cohort study
url https://diabetes.jmir.org/2025/1/e60141
work_keys_str_mv AT alycesadams estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT catherinelee estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT gabrielescobar estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT elizabethabayliss estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT briancallaghan estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT michaelhorberg estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT julieaschmittdiel estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT connietrinacty estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT lisakgilliam estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT eileenkim estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT nimashejazi estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT linma estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy
AT romainneugebauer estimatingtheriskoflowerextremitycomplicationsinadultsnewlydiagnosedwithdiabeticpolyneuropathyretrospectivecohortstudy