Background: Postprandial (PP) control remains a challenge for closed-loop (CL) systems. Few studies with inconsistent results have systematically investigated the PP period. Objective: To compare a new CL algorithm with current pump therapy (open loop [OL]) in the PP glucose control in type 1 diabetes (T1D) subjects. Methods: A crossover randomized study was performed in two centers. Twenty T1D subjects (F/M 13/7, age 40.7 ± 10.4 years, disease duration 22.6 ± 9.9 years, and A1c 7.8% ± 0.7%) underwent an 8-h mixed meal test on four occasions. In two (CL1/CL2), after meal announcement, a bolus was given followed by an algorithm-driven basal infusion based on continuous glucose monitoring (CGM). Alternatively, in OL1/OL2 conventional pump therapy was used. Main outcome measures were as follows: glucose variability, estimated with the coefficient of variation (CV) of the area under the curve (AUC) of plasma glucose (PG) and CGM values, and from the analysis of the glucose time series; mean, maximum (C_max), and time to C_max glucose concentrations and time in range (180 mg/dL). Results: CVs of the glucose AUCs were low and similar in all studies (around 10%). However, CL achieved greater reproducibility and better PG control in the PP period: CL1 = CL2<OL1<OL2 (PG_mean 123 ± 47 and 125 ± 44 vs. 152 ± 53 and 159 ± 54 mg/dL) and C_max OL 217.1 ± 67.0 mg/dL versus CL 183.3 ± 63.9 mg/dL, P < 0.0001. Time-in-range was higher with CL versus OL (80% vs. 64%; P < 0.001). Neither the time below 70 mg/dL (CL 6.1% vs. OL 3.2%; P > 0.05) nor the need for oral glucose was significantly different (CL 40.0% vs. OL 22.5% of meals; P = 0.054). Conclusions: This novel CL algorithm effectively and consistently controls PP glucose excursions without increasing hypoglycemia. Study registered at ClinicalTrials.gov: study number NCT02100488.

Background: With the proliferation of continuous glucose monitoring (CGM), a number of metrics were developed to assess quality of glycemic control. Many of them are highly correlated. Thus, we aim to identify the principal dimensions of glycemic control—a minimal set of metrics, necessary and sufficient for comprehensive assessment of diabetes management. Methods: Seventy-five thousand five hundred sixty-three 2-week CGM profiles recorded in six studies by 790 individuals with type 1 or type 2 diabetes were used to compute mean glucose (MG), percentage time >180 mg/dL (TAR), >250 mg/dL (TAR2), <70 mg/dL (TBR), <54 mg/dL (TBR2), and coefficient of variation (CV). The true dimensionality of the glycemic-metric space was identified in a training set (53,380 profiles) and validated in an independent test set (22,183 profiles). Results: Correlation analysis identified two blocks of metrics—(MG, TAR, TAR2) and (TBR, TBR2, CV)—each with high internal correlation, but insignificant between-block correlation, suggesting that the true dimensionality of the glycemic-metric space is 2. Principal component analysis confirmed two essential metrics quantifying exposure to hyperglycemia (i.e., treatment efficacy) and risk for hypoglycemia (i.e., treatment safety), and explaining ∼90% of the variance in the training and test data. Conclusion: Two essential metrics, treatment efficacy and treatment safety, are necessary and sufficient to characterize glycemic control in diabetes. Thus, quantitatively, diabetes treatment optimization is reduced to a two-dimensional problem, meaning that minimizing both exposure to hyperglycemia and risk for hypoglycemia will lead to improvement in any other metric of glycemic control.

Purpose Develop a diabetes diagnostic tool based on two markers of continuous glucose monitoring (CGM) dynamics: CGM entropy rate (ER) and Poincaré plot (PP) ellipse area (S). Methods 5,754 daily CGM profiles from 843 individuals with type 1, type 2 diabetes, or healthy individuals with or without islet autoantibody status were used to compute two individual dynamic markers: ER (in bits per transition; BPT) of daily probability matrices describing CGM transitions between eight glycemic states, and the area S (mg²/dL²) of individual CGM PP ellipses using standard PP descriptors. The Youden’s index was used to determine “optimal” cut-points for ER and S for health vs. diabetes (case 1); type 1 vs. type 2 (case 2); and low vs. high type 1 immunological risk (case 3). The markers’ discriminative power was assessed through the area under the receiver operating characteristics curves (AUC). Results Optimal cut-off points were determined for ER and S for each of the three cases. ER and S discriminated case 1 with AUC = 0.98 (95% CI: 0.97–0.99) and AUC = 0.99 (95% CI: 0.99–1.00), respectively, (cut-offs ER_case1 = 0.76 BPT, S_case1 = 1993.91 mg²/dL²), case 2 with AUC = 0.81 (95% CI, 0.77–0.84) and AUC = 0.76 (95% CI, 0.72–0.81), respectively (ER_case2 = 1.00 BPT, S_case2 = 5112.98 mg²/dL²), and case 3 with AUC = 0.81 (95% CI, 0.77–0.84) and AUC = 0.76 (95% CI, 0.72–0.81), respectively (ER_case3 = 0.52 BPT, S_case3 = 923.65 mg²/dL²). Conclusions CGM dynamics markers can be an alternative to fasting plasma glucose or glucose tolerance testing and identifying individuals at higher immunological risk of progressing to type 1 diabetes.

Background: Early identification of individuals at high risk for type 1 diabetes (T1D) is essential for timely intervention. Islet autoantibodies (AB) and continuous glucose monitoring (CGM) reveal early signs of glycemic dysregulation, while T1D genetic risk scores (GRS) further improve disease prediction. We use CGM data and T1D GRS to develop an AB classifier (1 AB vs. ≥2 AB) and predict early T1D risk. Methods: Thirty-nine AB-positive (18 with 1 and 21 with ≥2 AB) healthy relatives of T1D (mean age 22.1 ± 11.1 years, HbA1c 5.3 ± 0.3%, body mass index 24.1 ± 5.8 kg/m ² ) were enrolled in a National Institutes of Health’s (NIH) TrialNet ancillary study. Participants wore CGMs for a week and consumed three standardized liquid mixed meals (SLMM). Post-SLMM CGM glycemic features and T1D GRS were used in a linear support vector machine (SVM) model with recursive feature elimination (RFE) for AB classification, evaluated via fivefold cross-validation using the receiver operating characteristic and precision-recall area under the curve (AUC-ROC/PR). Results: Significant differences between the AB groups were observed in the post-SLMM percent time of glucose >180 mg/dL and GRS ( P = 0.020 and P = 0.001, respectively). An SVM model with two RFE-selected features (T1D GRS and incremental AUC) achieved the best performance, classifying 1 versus ≥2 AB individuals with an AUC-ROC of 0.93 (95% confidence interval [CI]: 0.83–1.00) and AUC-PR of 0.89 (95% CI: 0.71–0.99), compared with AUC-ROC of 0.80 (95% CI: 0.46–1.00) and AUC-PR of 0.82 (95% CI: 0.71–0.93) using all features. Conclusions: A machine learning approach combining a 1-week CGM home test and T1D GRS reliably assesses T1D immunological risk, enabling early intervention.

Background: Early detection and intervention are crucial for preventing vision-threatening diabetic retinopathy (DR) in adults with type 1 diabetes (T1D). This exploratory study uses machine learning on continuous glucose monitoring (CGM) data to identify factors influencing DR and predict high-risk individuals for timely intervention. Methods: Between June 2018 and March 2022, adults with T1D with incident DR or no retinopathy (control) were identified. The CGM data were collected retrospectively for up to seven years before the date of defining incident DR or no retinopathy. A mixture of three machine learning algorithms was trained and evaluated in two different scenarios, using different glycemic features extracted from CGM traces (scenario 1), and the two principal components (two PCs; exposure to hyperglycemia and hypoglycemia risk) of those features (scenario 2). Classifiers were evaluated through 10-fold cross-validation using the receiver operating characteristic area under the curve (AUC-ROC) to select the best classification model. Results: The CGM data of 30 adults with incident DR (mean±SD age of 21.2±9.4 years, glycated hemoglobin [HbA _1c ] of 8.6%±1.0%, and body mass index [BMI] of 24.5±4.8 kg/m ² ) and 30 adults without DR (age of 41.8±14.7 years, HbA _1c of 7.0%±0.9%, and BMI of 26.2±3.6 kg/m ² ) were included in this analysis. In scenario 2, classifiers outperformed scenario 1, resulting in an average AUC-ROC increase to 0.92 for two of three models, indicating that the two PCs captured vital classification data, representing the most discriminative aspects and enhancing model performance. Conclusion: Machine learning approaches using CGM data may have potential to aid in identifying adults with T1D at risk of DR.

This consensus report evaluates the potential role of continuous glucose monitoring (CGM) in screening for stage 2 type 1 diabetes (T1D). CGM offers a minimally invasive alternative to venous blood testing for detecting dysglycemia, facilitating early identification of at-risk individuals for confirmatory blood testing. A panel of experts reviewed current evidence and addressed key questions regarding CGM’s diagnostic accuracy and screening protocols. They concluded that while CGM cannot yet replace blood-based diagnostics, it holds promise as a screening tool that could lead to earlier, more effective intervention. Metrics such as time above range >140 mg/dL could indicate progression risk, and artificial intelligence (AI)-based modeling may enhance predictive capabilities. Further research is needed to establish CGM-based diagnostic criteria and refine screening strategies to improve T1D detection and intervention.