A Minimal Model Approach for Analyzing Continuous Glucose Monitoring in Type 2 Diabetes

Continuous glucose monitoring (CGM), a technique that records blood glucose at a regular intervals. While CGM is more commonly used in type 1 diabetes, it is increasingly becoming attractive for treating type 2 diabetic patients. The time series obtained from a CGM provides a rich picture of the glycemic state of the subjects and may help have tighter control on blood sugar by revealing patterns in their physiological responses to food. However, despite its importance, the biophysical understanding of CGM is far from complete. CGM data series is complex not only because it depends on the composition of the food but also varies with individual physiology. All of these make a full modeling of CGM data a difficult task. Here we propose a simple model to explain CGM data in type 2 diabetes. The model combines a relatively simple glucose-insulin dynamics with a two-compartment food model. Using CGM data of a healthy and a diabetic individual we show that this model can capture liquid meals well. The model also allows us to estimate the parameters in a relatively straightforward manner. This opens up the possibility of personalizing the CGM data. The model also predicts insulin time series from the model, and the rate of appearance of glucose due to food. Our methodology thus paves the way for novel analyses of CGM which have not been possible before.

[1]  K. Röbenack,et al.  ’ Electronic Copy OBSERVER BASED MEASUREMENT OF THE INPUT CURRENT OF A NEURON , 2006 .

[2]  Darrell M. Wilson,et al.  Factors Predictive of Severe Hypoglycemia in Type 1 Diabetes , 2011, Diabetes Care.

[3]  C. Chow,et al.  Modeling glucose and free fatty acid kinetics in glucose and meal tolerance test , 2016, Theoretical Biology and Medical Modelling.

[4]  Workgroup on Hypoglycemia Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. , 2005, Diabetes care.

[5]  C. Fidler,et al.  Hypoglycemia Event Rates: A Comparison Between Real-World Data and Randomized Controlled Trial Populations in Insulin-Treated Diabetes , 2016, Diabetes Therapy.

[6]  R. Miura,et al.  A model of beta-cell mass, insulin, and glucose kinetics: pathways to diabetes. , 2000, Journal of theoretical biology.

[7]  T. Christensen,et al.  The impact of non-severe hypoglycemic events on work productivity and diabetes management. , 2011, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[8]  Three-day continuous glucose monitoring for rapid assessment of hypoglycemic events and glycemic variability in type 1 diabetic patients. , 2011, Endocrine journal.

[9]  T. Bailey,et al.  The Performance and Usability of a Factory-Calibrated Flash Glucose Monitoring System , 2015, Diabetes technology & therapeutics.

[10]  S. Pereverzev,et al.  Glycemic Control Indices and Their Aggregation in the Prediction of Nocturnal Hypoglycemia From Intermittent Blood Glucose Measurements , 2016, Journal of diabetes science and technology.

[11]  C. McDonnell,et al.  A novel approach to continuous glucose analysis utilizing glycemic variation. , 2005, Diabetes technology & therapeutics.

[12]  Boris Kovatchev,et al.  Statistical tools to analyze continuous glucose monitor data. , 2009, Diabetes technology & therapeutics.

[13]  L. Magni,et al.  Diabetes: Models, Signals, and Control , 2010, IEEE Reviews in Biomedical Engineering.

[14]  P. Goel Insulin resistance or hypersecretion? The βIG picture revisited. , 2015, Journal of theoretical biology.

[15]  H. Murphy,et al.  Effectiveness of continuous glucose monitoring in pregnant women with diabetes: randomised clinical trial , 2008, BMJ : British Medical Journal.

[16]  B. Corkey Diabetes: Have We Got It All Wrong? , 2012, Diabetes Care.

[17]  J. Chase,et al.  Complexity of Continuous Glucose Monitoring Data in Critically Ill Patients: Continuous Glucose Monitoring Devices, Sensor Locations, and Detrended Fluctuation Analysis Methods , 2013, Journal of diabetes science and technology.

[18]  Eran Segal,et al.  Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses. , 2017, Cell metabolism.

[19]  Luigi del Re,et al.  Prediction Methods for Blood Glucose Concentration: Design, Use and Evaluation , 2016 .

[20]  D. Klonoff Continuous glucose monitoring: roadmap for 21st century diabetes therapy. , 2005, Diabetes care.

[21]  B. Bode,et al.  Clinical utility of the continuous glucose monitoring system. , 2000, Diabetes technology & therapeutics.

[22]  E. Segal,et al.  Personalized Nutrition by Prediction of Glycemic Responses , 2015, Cell.

[23]  J. Unger Uncovering undetected hypoglycemic events , 2012, Diabetes, metabolic syndrome and obesity : targets and therapy.

[24]  Jaime A. Moreno,et al.  Unknown input observers for SISO nonlinear systems , 2000, Proceedings of the 39th IEEE Conference on Decision and Control (Cat. No.00CH37187).

[25]  D. Ludwig,et al.  Increasing adiposity: consequence or cause of overeating? , 2014, JAMA.

[26]  Darrell M. Wilson,et al.  The effect of continuous glucose monitoring in well-controlled type 1 diabetes , 2010 .

[27]  P. Goel Theoretical Advances in Type 2 Diabetes , 2017 .