An Exploratory Study of Blood Glucose Estimation from Photoplethysmography Signals using Machine Learning

Non-invasive blood glucose level (BGL) estimation from photoplethysmography (PPG) holds great promise for wearable health monitoring, but results across studies are hard to compare due to inconsistent datasets, data leakage, and non-standardized evaluation metrics. We present the first reproducible, extensible evaluation pipeline and use it to reassess five representative PPG-based BGL methods on published datasets under three increasingly strict data-split protocols: random window-level, participant-aware, and leave-some-participants-out (LSPO). Models appeared competitive under random splitting but collapsed under participant-aware and LSPO evaluation, with nearly all yielding near-zero or negative R$^2$ values comparable to a mean-prediction baseline. Critically, across every model and split, over 90% of predictions fell within clinically acceptable zones (Clarke Error Grid A+B), including the baseline. This reveals a fundamental disconnect: clinical zone metrics systematically conceal model failure in this domain. Our findings demonstrate that random train-test splits substantially overestimate the generalization of PPG-based BGL models due to sample-level data leakage, and that robust ML evaluation must precede clinical validation to meaningfully assess real-world utility.

Continuous cuffless blood pressure (BP) monitoring is essential for connected health systems and wearable devices, enabling early detection, longitudinal tracking, and personalized management of cardiovascular disease. Many prior approaches attempt to estimate BP indirectly by reconstructing electrocardiography (ECG) from photoplethysmography (PPG), assuming ECG provides a stronger physiological link to BP. However, ECG sensing is less accessible in wearable settings and may introduce unnecessary complexity. In this work, we first perform a large-scale physiological correlation analysis on the MIMIC-III waveform database, revealing that PPG exhibits substantially stronger coupling with arterial blood pressure (ABP) ($|r|=0.247$, $p<0.001$) than ECG does ($r=0.018$, $p=0.187$), challenging the assumption that ECG provides a superior intermediate representation. Motivated by this insight, we conduct a systematic comparison between direct PPG-to-BP prediction and ECG-mediated pipelines using multiple state-of-the-art deep learning models. Across 1.74M segments from 3,127 patients, direct PPG-to-BP prediction achieves British Hypertension Society Grade A performance ($\mathrm{MAE}_{\mathrm{SBP}} = 4.82 mmHg$, $\mathrm{MAE}_{\mathrm{DBP}} = 4.31 mmHg$), outperforming all ECG-mediated approaches, which achieve only Grade B accuracy. Our findings suggest that accurate continuous BP monitoring can be achieved directly from wearable PPG signals, enabling simpler, more efficient pipelines for real-world connected health systems.

Artificial intelligence (AI) algorithms are a critical part of state-of-the-art digital health technology for diabetes management. Yet, access to large high-quality datasets is creating barriers that impede development of robust AI solutions. To accelerate development of transparent, reproducible, and robust AI solutions, we present Glucose-ML, a collection of 10 publicly available diabetes datasets, released within the last 7 years (i.e., 2018 - 2025). The Glucose-ML collection comprises over 300,000 days of continuous glucose monitor (CGM) data with a total of 38 million glucose samples collected from 2500+ people across 4 countries. Participants include persons living with type 1 diabetes, type 2 diabetes, prediabetes, and no diabetes. To support researchers and innovators with using this rich collection of diabetes datasets, we present a comparative analysis to guide algorithm developers with data selection. Additionally, we conduct a case study for the task of blood glucose prediction - one of the most common AI tasks within the field. Through this case study, we provide a benchmark for short-term blood glucose prediction across all 10 publicly available diabetes datasets within the Glucose-ML collection. We show that the same algorithm can have significantly different prediction results when developed/evaluated with different datasets. Findings from this study are then used to inform recommendations for developing robust AI solutions within the diabetes or broader health domain. We provide direct links to each longitudinal diabetes dataset and openly provide our code.