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1. Temporal Glycemic Patterns in Type 1 and Type 2 Diabetes: Insights From Extended Continuous Glucose Monitoring

   https://doi.org/10.1177/19322968251341264  

   Okuno, Tomoki; Sort, Lucas; Zhang, Bowen; Zhou, Kerry; Kitchen, Matthew; Li, Victor; Miller, Donald R; Norman, Gregory J; Reaven, Peter; Zhou, Jin J (May 2025, Journal of Diabetes Science and Technology)

   Background:Achieving optimal glycemic control for persons with diabetes remains difficult. Real-world continuous glucose monitoring (CGM) data can illuminate previously underrecognized glycemic fluctuations. We aimed to characterize glucose trajectories in individuals with Type 1 and Type 2 diabetes, and to examine how baseline glycemic control, CGM usage frequency, and regional differences shape these patterns. Methods:We linked Dexcom CGM data (2015–2020) with Veterans Health Administration electronic health records, identifying 892 Type 1 and 1716 Type 2 diabetes patients. Analyses focused on the first three years of CGM use, encompassing over 2.1 million glucose readings. We explored temporal trends in average daily glucose and time-in-range values. Results:Both Type 1 and Type 2 cohorts exhibited a gradual rise in mean daily glucose over time, although higher CGM usage frequency was associated with lower overall glucose or attenuated increases. Notable weekly patterns emerged: Sundays consistently showed the highest glucose values, whereas Wednesdays tended to have the lowest. Seasonally, glycemic control deteriorated from October to February and rebounded from April to August, with more pronounced fluctuations in the Northeast compared to the Southwest U.S. Conclusions:Our findings underscore the importance of recognizing day-of-week and seasonal glycemic variations in diabetes management. Tailoring interventions to account for these real-world fluctuations may enhance patient engagement, optimize glycemic control, and ultimately improve health outcomes. 

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2. Heterogeneous treatment effects of intensive glycemic control on major adverse cardiovascular events in the ACCORD and VADT trials: a machine-learning analysis

   https://doi.org/10.1186/s12933-022-01496-7  

   Edward, Justin A.; Josey, Kevin; Bahn, Gideon; Caplan, Liron; Reusch, Jane E.; Reaven, Peter; Ghosh, Debashis; Raghavan, Sridharan (December 2022, Cardiovascular Diabetology)

   Abstract Background Evidence to guide type 2 diabetes treatment individualization is limited. We evaluated heterogeneous treatment effects (HTE) of intensive glycemic control in type 2 diabetes patients on major adverse cardiovascular events (MACE) in the Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) and the Veterans Affairs Diabetes Trial (VADT). Methods Causal forests machine learning analysis was performed using pooled individual data from two randomized trials (n = 12,042) to identify HTE of intensive versus standard glycemic control on MACE in patients with type 2 diabetes. We used variable prioritization from causal forests to build a summary decision tree and examined the risk difference of MACE between treatment arms in the resulting subgroups. Results A summary decision tree used five variables (hemoglobin glycation index, estimated glomerular filtration rate, fasting glucose, age, and body mass index) to define eight subgroups in which risk differences of MACE ranged from − 5.1% (95% CI − 8.7, − 1.5) to 3.1% (95% CI 0.2, 6.0) (negative values represent lower MACE associated with intensive glycemic control). Intensive glycemic control was associated with lower MACE in pooled study data in subgroups with low (− 4.2% [95% CI − 8.1, − 1.0]), intermediate (− 5.1% [95% CI − 8.7, − 1.5]), and high (− 4.3% [95% CI − 7.7, − 1.0]) MACE rates with consistent directions of effect in ACCORD and VADT alone. Conclusions This data-driven analysis provides evidence supporting the diabetes treatment guideline recommendation of intensive glucose lowering in diabetes patients with low cardiovascular risk and additionally suggests potential benefits of intensive glycemic control in some individuals at higher cardiovascular risk. 

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3. Hypoglycemia and hyperglycemia detection using ECG: A multi-threshold based personalized fusion model

   Dave, Darpit; Vyas, Kathan; Cote, Gerard; Erraguntla, Madhav (July 2024, Biomedical signal processing and control)

   Monitoring glucose levels is critical for effective diabetes management. Continuous glucose monitoring devices estimate interstitial glucose levels and provide alerts for glycemic excursions. However, they are expensive and invasive. Therefore, low-cost, noninvasive alternatives are useful for patients with diabetes. In this article, we explore electrocardiogram signals as a potential alternative to detecting glycemic excursions by extracting intrabeat (beat-morphology) and inter-beat (heart rate variability) information. Unlike prior methods that focused only on the standard clinical excursion thresholds (70 mg/dL for hypoglycemia, 180 mg/dL for hyperglycemia), our proposed approach trains independent machine learning models at various excursion thresholds, aggregating their outputs for a final prediction. This allows learning morphological patterns in the neighborhood of the standard excursion thresholds. Our personalized fusion models achieve an AUC of 75 % for hypoglycemia and 78% for hyperglycemia detection across patients, resulting in an average improvement of 4 % compared to the baseline models (trained using only standard clinical thresholds) for detecting glycemic excursions. We also find that combining morphology and HRV information outperforms using them individually (5 % for hypoglycemia and 6 % for hyperglycemia). The data used in this article was collected from 12 patients with type-1 diabetes, each monitored over a 14-day period at Texas Children’s Hospital, Houston. The results indicate that a combination of morphological and HRV features is essential for noninvasive detection of glycemic excursions. Also, morphological changes can happen at varying glucose levels for different patients and capturing these changes provide valuable information that leads to improved prediction performance for detecting glycemic excursions. 

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4. Association of Both Short-term and Long-term Glycemic Variability With the Development of Microalbuminuria in the ACCORD Trial

   https://doi.org/10.2337/db23-0374  

   Okuno, Tomoki; Vansomphone, Arin; Zhang, Elyse; Zhou, Hua; Koska, Juraj; Reaven, Peter; Zhou, Jin J. (September 2023, Diabetes)

   Both long- and short-term glycemic variability have been associated with incident diabetes complications. We evaluated their relative and potential additive effects on incident renal complications in the Action to Control Cardiovascular Risk in Diabetes trial. A marker of short-term glycemic variability, 1,5-anhydroglucitol (1,5-AG), was measured in 4,000 random 12-month postrandomization plasma samples (when hemoglobin A1c [HbA1c] was stable). Visit-to-visit fasting plasma glucose coefficient of variation (CV-FPG) was determined from 4 months postrandomization until the end point of microalbuminuria or macroalbuminuria. Using Cox proportional hazards models, high CV-FPG and low 1,5-AG were independently associated with microalbuminuria after adjusting for clinical risk factors. However, only the CV-FPG association remained after additional adjustment for average HbA1c. Only CV-FPG was a significant risk factor for macroalbuminuria. This post hoc analysis indicates that long-term rather than short-term glycemic variability better predicts the risk of renal disease in type 2 diabetes. Article HighlightsThe relative and potential additive effects of long- and short-term glycemic variability on the development of diabetic complications are unknown. We aimed to assess the individual and combined relationships of long-term visit-to-visit glycemic variability, measured as the coefficient of variation of fasting plasma glucose, and short-term glucose fluctuation, estimated by the biomarker 1,5-anhydroglucitol, with the development of proteinuria. Both estimates of glycemic variability were independently associated with microalbuminuria, but only long-term glycemic variability remained significant after adjusting for average hemoglobin A1c. Our findings suggest that longer-term visit-to-visit glucose variability improves renal disease prediction in type 2 diabetes. 

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5. Privacy-Preserving Glycemic Management in Type 1 Diabetes: Development and Validation of a Multiobjective Federated Reinforcement Learning Framework

   https://doi.org/10.2196/72874  

   Sarani_Rad, Fatemeh; Li, Juan (July 2025, JMIR Diabetes)

   Abstract BackgroundEffective diabetes management requires precise glycemic control to prevent both hypoglycemia and hyperglycemia, yet existing machine learning (ML) and reinforcement learning (RL) approaches often fail to balance competing objectives. Traditional RL-based glucose regulation systems primarily focus on single-objective optimization, overlooking factors such as minimizing insulin overuse, reducing glycemic variability, and ensuring patient safety. Furthermore, these approaches typically rely on centralized data processing, which raises privacy concerns due to the sensitive nature of health care data. There is a critical need for a decentralized, privacy-preserving framework that can personalize blood glucose regulation while addressing the multiobjective nature of diabetes management. ObjectiveThis study aimed to develop and validate PRIMO-FRL (Privacy-Preserving Reinforcement Learning for Individualized Multi-Objective Glycemic Management Using Federated Reinforcement Learning), a novel framework that optimizes clinical objectives—maximizing time in range (TIR), reducing hypoglycemia and hyperglycemia, and minimizing glycemic risk—while preserving patient privacy. MethodsWe developed PRIMO-FRL, integrating multiobjective reward shaping to dynamically balance glucose stability, insulin efficiency, and risk reduction. The model was trained and tested using simulated data from 30 simulated patients (10 children, 10 adolescents, and 10 adults) generated with the Food and Drug Administration (FDA)–approved UVA/Padova simulator. A comparative analysis was conducted against state-of-the-art RL and ML models, evaluating performance using metrics such as TIR, hypoglycemia (<70 mg/dL), hyperglycemia (>180 mg/dL), and glycemic risk scores. ResultsThe PRIMO-FRL model achieved a robust overall TIR of 76.54%, with adults demonstrating the highest TIR at 81.48%, followed by children at 77.78% and adolescents at 70.37%. Importantly, the approach eliminated hypoglycemia, with 0.0% spent below 70 mg/dL across all cohorts, significantly outperforming existing methods. Mild hyperglycemia (180-250 mg/dL) was observed in adolescents (29.63%), children (22.22%), and adults (18.52%), with adults exhibiting the best control. Furthermore, the PRIMO-FRL approach consistently reduced glycemic risk scores, demonstrating improved safety and long-term stability in glucose regulation.. ConclusionsOur findings highlight the potential of PRIMO-FRL as a transformative, privacy-preserving approach to personalized glycemic management. By integrating federated RL, this framework eliminates hypoglycemia, improves TIR, and preserves data privacy by decentralizing model training. Unlike traditional centralized approaches that require sharing sensitive health data, PRIMO-FRL leverages federated learning to keep patient data local, significantly reducing privacy risks while enabling adaptive and personalized glucose control. This multiobjective optimization strategy offers a scalable, secure, and clinically viable solution for real-world diabetes care. The ability to train personalized models across diverse populations without exposing raw data makes PRIMO-FRL well-suited for deployment in privacy-sensitive health care environments. These results pave the way for future clinical adoption, demonstrating the potential of privacy-preserving artificial intelligence in optimizing glycemic regulation while maintaining security, adaptability, and personalization. 

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