arXiv subjects

Francisco Gude

Publications and source records attributed to Francisco Gude.

8 recordsLinked to original sources

arXiv2025

Beyond Scalar Metrics: Functional Data Analysis of Postprandial Continuous Glucose Monitoring in the AEGIS Study

Postprandial glucose collected through continuous glucose monitoring (CGM) provides critical information for assessing metabolic capacity and guiding dietary recommendations. Traditional approaches summarize these data into scalar measures, such as 2-hour AUC or peak glucose, potentially overlooking temporal dynamics. We propose analyzing entire CGM trajectories using multilevel functional data analysis (FDA), which accounts for the smooth, hierarchical nature of glucose responses. Applying these methods to AEGIS study participants without diabetes, we illustrate how FDA characterizes variability in postprandial responses and links dietary/patient characteristics to glucose dynamics. We further extend the r-square metric to hierarchical functional models to quantify explanatory power. Our results show that dietary effects vary across the 6-hour postprandial window-for example, fiber blunts responses after 90 minutes, while fats reduce early rises within 50 minutes. Moreover, metabolic responses differ between normoglycemic and prediabetic individuals. These findings demonstrate that functional approaches reveal temporal and stratified insights into postprandial glucose regulation that scalar methods cannot capture.

q-bio.QM↗

arXiv2025

Optimal Cut-Point Estimation for Functional Digital Biomarkers: Application to Diabetes Risk Stratification via Continuous Glucose Monitoring

Establishing optimal cut-offs for clinical biomarkers is a fundamental statistical problem in epidemiology, clinical trials, and drug discovery. While there is extensive literature regarding the definition of optimal cut-offs for scalar biomarkers, methodologies for analyzing random statistical objects in the more complex spaces associated with random functions and graphs - something increasingly required in the field of modern digital health applications - are lacking. This paper proposes a new, general, simple methodology for defining optimal cut-offs for random objects residing in separable Hilbert spaces. Its underlying motivation is the need to create new, digital health rules for the detection of diabetes mellitus, and thus better exploit the continuous high-dimensional functional information provided by continuous glucose monitors (CGM). A functional cut-off for identifying diabetes is offered, based on glucose distributional representations from CGM time series. This work may be a valuable resource for researchers interested in defining and validating new digital biomarkers for biosensor time series

stat.ME↗

arXiv2025

From Glucose Patterns to Health Outcomes: A Generalizable Foundation Model for Continuous Glucose Monitor Data Analysis

Recent advances in SSL enabled novel medical AI models, known as foundation models, offer great potential for better characterizing health from diverse biomedical data. CGM provides rich, temporal data on glycemic patterns, but its full potential for predicting broader health outcomes remains underutilized. Here, we present GluFormer, a generative foundation model for CGM data that learns nuanced glycemic patterns and translates them into predictive representations of metabolic health. Trained on over 10 million CGM measurements from 10,812 adults, primarily without diabetes, GluFormer uses autoregressive token prediction to capture longitudinal glucose dynamics. We show that GluFormer generalizes to 19 external cohorts (n=6,044) spanning different ethnicities and ages, 5 countries, 8 CGM devices, and diverse pathophysiological states. GluFormers representations exceed the performance of current CGM metrics, such as the Glucose Management Indicator (GMI), for forecasting clinical measures. In a longitudinal study of 580 adults with CGM data and 12-year follow-up, GluFormer identifies individuals at elevated risk of developing diabetes more effectively than blood HbA1C%, capturing 66% of all new-onset diabetes diagnoses in the top quartile versus 7% in the bottom quartile. Similarly, 69% of cardiovascular-death events occurred in the top quartile with none in the bottom quartile, demonstrating powerful risk stratification beyond traditional glycemic metrics. We also show that CGM representations from pre-intervention periods in Randomized Clinical Trials outperform other methods in predicting primary and secondary outcomes. When integrating dietary data into GluFormer, we show that the multi-modal version of the model can accurately generate CGM data based on dietary intake data, simulate outcomes of dietary interventions, and predict individual responses to specific foods.

q-bio.QM↗

arXiv2024

Glucodensity Functional Profiles Outperform Traditional Continuous Glucose Monitoring Metrics

Continuous glucose monitoring (CGM) data has revolutionized the management of type 1 diabetes, particularly when integrated with insulin pumps to mitigate clinical events such as hypoglycemia. Recently, there has been growing interest in utilizing CGM devices in clinical studies involving healthy and diabetes populations. However, efficiently exploiting the high temporal resolution of CGM profiles remains a significant challenge. Numerous indices -- such as time-in-range metrics and glucose variability measures -- have been proposed, but evidence suggests these metrics overlook critical aspects of glucose dynamic homeostasis. As an alternative method, this paper explores the clinical value of glucodensity metrics in capturing glucose dynamics -- specifically the speed and acceleration of CGM time series -- as new biomarkers for predicting long-term glucose outcomes. Our results demonstrate significant information gains, exceeding 20\% in terms of adjusted $R^2$, in forecasting glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) at five and eight years from baseline AEGIS data, compared to traditional non-CGM and CGM glucose biomarkers. These findings underscore the importance of incorporating more complex CGM functional metrics, such as the glucodensity approach, to fully capture continuous glucose fluctuations across different time-scale resolutions.

stat.AP↗

arXiv2024

Personalized Imputation in metric spaces via conformal prediction: Applications in Predicting Diabetes Development with Continuous Glucose Monitoring Information

The challenge of handling missing data is widespread in modern data analysis, particularly during the preprocessing phase and in various inferential modeling tasks. Although numerous algorithms exist for imputing missing data, the assessment of imputation quality at the patient level often lacks personalized statistical approaches. Moreover, there is a scarcity of imputation methods for metric space based statistical objects. The aim of this paper is to introduce a novel two-step framework that comprises: (i) a imputation methods for statistical objects taking values in metrics spaces, and (ii) a criterion for personalizing imputation using conformal inference techniques. This work is motivated by the need to impute distributional functional representations of continuous glucose monitoring (CGM) data within the context of a longitudinal study on diabetes, where a significant fraction of patients do not have available CGM profiles. The importance of these methods is illustrated by evaluating the effectiveness of CGM data as new digital biomarkers to predict the time to diabetes onset in healthy populations. To address these scientific challenges, we propose: (i) a new regression algorithm for missing responses; (ii) novel conformal prediction algorithms tailored for metric spaces with a focus on density responses within the 2-Wasserstein geometry; (iii) a broadly applicable personalized imputation method criterion, designed to enhance both of the aforementioned strategies, yet valid across any statistical model and data structure. Our findings reveal that incorporating CGM data into diabetes time-to-event analysis, augmented with a novel personalization phase of imputation, significantly enhances predictive accuracy by over ten percent compared to traditional predictive models for time to diabetes.

stat.ME↗

arXiv2022

Hypothesis testing for matched pairs with missing data by maximum mean discrepancy: An application to continuous glucose monitoring

A frequent problem in statistical science is how to properly handle missing data in matched paired observations. There is a large body of literature coping with the univariate case. Yet, the ongoing technological progress in measuring biological systems raises the need for addressing more complex data, e.g., graphs, strings and probability distributions, among others. In order to fill this gap, this paper proposes new estimators of the maximum mean discrepancy (MMD) to handle complex matched pairs with missing data. These estimators can detect differences in data distributions under different missingness mechanisms. The validity of this approach is proven and further studied in an extensive simulation study, and results of statistical consistency are provided. Data from continuous glucose monitoring in a longitudinal population-based diabetes study are used to illustrate the application of this approach. By employing the new distributional representations together with cluster analysis, new clinical criteria on how glucose changes vary at the distributional level over five years can be explored.

stat.ME↗

arXiv2020

Glucose values prediction five years ahead with a new framework of missing responses in reproducing kernel Hilbert spaces, and the use of continuous glucose monitoring technology

AEGIS study possesses unique information on longitudinal changes in circulating glucose through continuous glucose monitoring technology (CGM). However, as usual in longitudinal medical studies, there is a significant amount of missing data in the outcome variables. For example, 40 percent of glycosylated hemoglobin (A1C) biomarker data are missing five years ahead. With the purpose to reduce the impact of this issue, this article proposes a new data analysis framework based on learning in reproducing kernel Hilbert spaces (RKHS) with missing responses that allows to capture non-linear relations between variable studies in different supervised modeling tasks. First, we extend the Hilbert-Schmidt dependence measure to test statistical independence in this context introducing a new bootstrap procedure, for which we prove consistency. Next, we adapt or use existing models of variable selection, regression, and conformal inference to obtain new clinical findings about glucose changes five years ahead with the AEGIS data. The most relevant findings are summarized below: i) We identify new factors associated with long-term glucose evolution; ii) We show the clinical sensibility of CGM data to detect changes in glucose metabolism; iii) We can improve clinical interventions based on our algorithms' expected glucose changes according to patients' baseline characteristics.

stat.ML↗

arXiv2020

Glucodensities: a new representation of glucose profiles using distributional data analysis

Biosensor data has the potential ability to improve disease control and detection. However, the analysis of these data under free-living conditions is not feasible with current statistical techniques. To address this challenge, we introduce a new functional representation of biosensor data, termed the glucodensity, together with a data analysis framework based on distances between them. The new data analysis procedure is illustrated through an application in diabetes with continuous-time glucose monitoring (CGM) data. In this domain, we show marked improvement with respect to state of the art analysis methods. In particular, our findings demonstrate that i) the glucodensity possesses an extraordinary clinical sensitivity to capture the typical biomarkers used in the standard clinical practice in diabetes, ii) previous biomarkers cannot accurately predict glucodensity, so that the latter is a richer source of information, and iii) the glucodensity is a natural generalization of the time in range metric, this being the gold standard in the handling of CGM data. Furthermore, the new method overcomes many of the drawbacks of time in range metrics, and provides deeper insight into assessing glucose metabolism.

stat.AP↗