Adaptive Biobehavioral Control: A Pilot Analysis of Human-Machine Coadaptation in Type 1 Diabetes.

Background: While it is well recognized that an automated insulin delivery (AID) algorithm should adapt to changes in physiology, it is less understood that the individual would also have to adapt to the AID system. The adaptive biobehavioral control (ABC) method presented here attempts to compensate for this deficiency by including AID into an information cloud-based ecosystem. Methods: The Web Information Tool (WIT) implements the ABC concept via the following: (1) a Physiological Adaptation Module (PAM) that tracks metabolic changes and adapts AID parameters accordingly and (2) a Behavioral Adaptation Module (BAM) that provides information feedback. The safety of WIT (primary outcome) was assessed in an 8-week randomized, two-arm parallel pilot study. All participants used the Control-IQ® AID system enhanced with PAM, but only those in the Experimental group had access to BAM. Secondary glycemic outcomes were computed using the 2-week baseline period and the last 2 weeks of treatment. Results: Thirty participants with type 1 diabetes (T1D) completed all study procedures (17 female/13 male; age: 40 ± 14 years; HbA1c: 6.6% ± 0.5%). No severe hypoglycemia, DKA, or other serious adverse events were reported. Comparing the Experimental and Control groups, no significant difference was observed in time in range (70-180 mg/dL): 74.6% vs 73.8%, adjusted mean difference: 2.65%, 95% CI (-1.12%,6.41%), P = 0.161. Time in 70-140 mg/dL was significantly higher in the Experimental group: 50.7% vs 49.2%, 5.71% (0.44%,10.97%), P = 0.035, without increased time below range: 0.54% (-0.09%,1.17%), P = 0.089. Conclusion: The results demonstrate that it is safe to integrate an AID system into the WIT ecosystem. Validation in a full-scale study is ongoing.

Clinically Similar Clusters of Daily Continuous Glucose Monitoring Profiles: Tracking the Progression of Glycemic Control Over Time.

Background: The adoption of continuous glucose monitoring (CGM) results in vast amounts of data, but their interpretation is still more art than exact science. The International Consensus on Time in Range (TIR) proposed the widely accepted TIR system of metrics, which we now take forward by introducing a finite and fixed set of clinically similar clusters (CSCs), such that the TIR metrics of daily CGM profiles within a cluster are homogeneous. Methods: CSC definition and validation used 204,710 daily CGM profiles in health, and types 1 and 2 diabetes (T1D and T2D) on different treatments. The CSCs were defined using 23,916 daily CGM profiles (Training set), and the final fixed set of CSCs was obtained using another 37,758 profiles (Validation set). The Testing set (143,036 profiles) was used to establish the robustness and generalizability of CSCs. Results: The final set of CSCs contains 32 clusters. Any daily CGM profile was classifiable to a single CSC, which approximated common glycemic metrics of the daily CGM profile, as evidenced by regression analyses with 0 intercept (R-squares ≥0.83, e.g., correlation ≥0.91), for all TIR and several other metrics. The CSCs distinguished CGM profiles in health, T2D, and T1D on different treatments, and allowed tracking of daily changes in a person's glycemic control over time. Conclusion: Daily CGM profiles can be classified into one of 32 prefixed CSCs, which enables a host of applications, for example, tabulated data interpretation and algorithmic approaches to treatment, database indexing, pattern recognition, and tracking disease progression. Clinical Trial Registration: N/A-not a clinical trial.

External validation of a classifier of daily continuous glucose monitoring (CGM) profiles.

As continuous glucose monitoring (CGM) sensors generate ever increasing amounts of CGM data, the need for methods to simplify the storage and analysis of this data becomes increasingly important. Lobo et al. developed a classifier of daily CGM profiles as an initial step in addressing this need. The classifier has several important applications including, but not limited to, data compression, data encryption, and indexing of databases. While the classifier has already successfully classified 99.0% of the 42,595 daily CGM profiles in a Test Set, this work presents an external validation using an external validation set (EVal Set) derived from 8 publicly available data sets. The Test Set and the EVal Set differ in terms of (but not limited to) demographics, data collection time periods, and data collection geographies. The classifier successfully classified 98.2% of the 137,030 daily CGM profiles in the EVal Set. Furthermore, each of the 483 distinct groups of classified daily CGM profiles from the EVal Set retains the same clinical characteristics as the corresponding group from the Test Set, as desired. Finally, the set of unclassified daily CGM profiles from the EVal Set retains the same statistical characteristics as the set of unclassified daily CGM profiles from the Test Set, as desired. These results establish the robustness and generalizability of the classifier: the performance of the classifier is unchanged despite the marked differences between the Test Set and the EVal Set.

A Data-Driven Approach to Classifying Daily Continuous Glucose Monitoring (CGM) Time Series.

According to the World Health Organization, about 422 million people worldwide have type 1 or type 2 diabetes (T1D, T2D), with the latter accounting for 90-95% of cases. Safe and effective treatment of patients with diabetes requires accurate and frequent monitoring of their blood sugar levels. Continuous glucose monitoring (CGM) is a monitoring technology developed to address this need, and its use among U.S. T1D patients has increased from 6% in 2011 to 38% in 2018 and continues to increase worldwide in both T1D and T2D. This paper presents a data-driven approach to determine Ω, a finite set of representative daily profiles (motifs) such that almost any daily CGM profile generated by a patient can be matched to one of the motifs in Ω. The training data set (9741 profiles) was used to identify 8 candidate sets of motifs, while the validation data set (14 175 profiles) was used to select the final set Ω. The robustness of Ω was established by using it to successfully classify (match against a representative daily profile in Ω) 99.0% of 42 595 daily CGM profiles in the testing data set. All data sets contained daily CGM profiles from six studies involving T1D and T2D patients using a variety of treatment modes, including daily insulin injections, insulin pumps, or artificial pancreas (AP). The classified profiles can be used in predictive modeling, decision support, and automated control systems (e.g., AP).

A recurrent neural network approach to predicting hemoglobin trajectories in patients with End-Stage Renal Disease.

The most severe form of kidney disease, End-Stage Renal Disease (ESRD) is treated with various forms of dialysis - artificial blood cleansing. Dialysis patients suffer many health burdens including high mortality and hospitalization rates, and symptomatic anemia: a low red blood cell count as indicated by a low hemoglobin (Hgb) level. ESRD-induced anemia is treated, with variable patient response, by erythropoiesis stimulating agents (ESAs): expensive injectable medications typically administered during dialysis sessions. The dosing protocol is typically a population level protocol based on original clinical trials, the use of which often results in Hgb cycling. This cycling phenomenon occurs primarily due to the mismatch in the time between dosing decisions and the time it takes for the effects of a dosing change to be fully realized. In this paper we develop a recurrent neural network approach that uses historic data together with future ESA and iron dosing data to predict the 1, 2, and 3 month Hgb levels of patients with ESRD-induced anemia. The results of extensive experimentation indicate that this approach generates predictions that are clinically relevant: the mean absolute error of the predictions is comparable to estimates of the intra-individual variability of the laboratory test for Hgb.