Developing a physiological model for type II diabetes mellitus

High blood glucose levels in type II diabetic patients often result from the malfunction of different organs such as the pancreas, the liver, muscles, and adipose tissues. Accurate diagnosis of abnormalities associated with type II diabetic patients is essential for administering an effective treatment. In this paper, a model for type II diabetes has been developed based on a detailed compartmental physiological model proposed for a healthy human body. Using available clinical data from type II diabetic patients, the model parameters have been estimated by means of an optimization method for diabetic patients. The estimated model may be used to understand the behavior of different organs in type II diabetic patients. It has been shown that the proposed model can predict the relative deficiency in the pancreatic insulin production, the impaired hepatic regulatory effect on glucose concentrations, and the low peripheral glucose uptake in type II diabetic patients.

[1]  C. Cobelli,et al.  Validation of mathematical models of complex endocrine-metabolic systems. A case study on a model of glucose regulation , 1983, Medical and Biological Engineering and Computing.

[2]  D. U. Campos-Delgado,et al.  An extension to the compartmental model of type 1 diabetic patients to reproduce exercise periods with glycogen depletion and replenishment. , 2008, Journal of biomechanics.

[3]  R. Rizza,et al.  Insulin dose-response curves for stimulation of splanchnic glucose uptake and suppression of endogenous glucose production differ in nondiabetic humans and are abnormal in people with type 2 diabetes. , 2004, Diabetes.

[4]  K Tokuyama,et al.  Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach. , 1999, Diabetes.

[5]  L. Groop,et al.  Insulin resistance and insulin deficiency in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus: errors of metabolism or of methods? , 1993, Diabetologia.

[6]  T. Méas,et al.  Abnormalities in insulin secretion in type 2 diabetes mellitus. , 2008, Diabetes & metabolism.

[7]  J. Leahy.  Pathogenesis of type 2 diabetes mellitus. , 2005, Archives of medical research.

[8]  R. Rizza,et al.  Both fasting glucose production and disappearance are abnormal in people with "mild" and "severe" type 2 diabetes. , 2004, American journal of physiology. Endocrinology and metabolism.

[9]  R. DeFronzo,et al.  Pathogenesis of NIDDM: A Balanced Overview , 1992, Diabetes Care.

[10]  Yang Kuang,et al.  Mathematical models and software tools for the glucose-insulin regulatory system and diabetes: an overview , 2006 .

[11]  R. DeFronzo,et al.  Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake. , 1989, Metabolism: clinical and experimental.

[12]  Dale E. Seborg,et al.  An Improved PID Switching Control Strategy for Type 1 Diabetes , 2008, IEEE Transactions on Biomedical Engineering.

[13]  J. Halter,et al.  Insulin secretion in diabetes mellitus. , 1981, The American journal of medicine.

[14]  Claudio Cobelli,et al.  Effects of Type 2 Diabetes on Insulin Secretion, Insulin Action, Glucose Effectiveness, and Postprandial Glucose Metabolism , 2009, Diabetes Care.

[15]  F. Capani,et al.  Predominant Role of Gluconeogenesis in Increased Hepatic Glucose Production in NIDDM , 1989, Diabetes.

[16]  R. Rizza,et al.  Obesity and type 2 diabetes impair insulin-induced suppression of glycogenolysis as well as gluconeogenesis. , 2005, Diabetes.

[17]  Gade Pandu Rangaiah,et al.  Robust PID controller for blood glucose regulation in type I diabetics , 2004 .

[18]  T. Jenssen,et al.  Contribution of Abnormal Muscle and Liver Glucose Metabolism to Postprandial Hyperglycemia in NIDDM , 1990, Diabetes.

[19]  Francis J. Doyle,et al.  Robust H∞ glucose control in diabetes using a physiological model , 2000 .

[20]  C. Bogardus,et al.  The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. , 1999, The Journal of clinical investigation.

[21]  M. Jensen,et al.  Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity. , 2000, Diabetes.

[22]  Nicholas A Peppas,et al.  Effectiveness of Intravenous Infusion Algorithms for Glucose Control in Diabetic Patients Using Different Simulation Models. , 2009, Industrial & engineering chemistry research.

[23]  R. DeFronzo,et al.  The disposal of an oral glucose load in patients with non-insulin-dependent diabetes. , 1988, Metabolism: clinical and experimental.

[24]  W. Rhoten.  Perifusion of saurian pancreatic islets and biphasic insulin release following glucose stimulation. , 1973, Comparative biochemistry and physiology. A, Comparative physiology.

[25]  P. Iozzo,et al.  Inverse association between liver fat content and hepatic glucose uptake in patients with type 2 diabetes mellitus. , 2008, Metabolism: clinical and experimental.

[26]  P. Iozzo,et al.  Insulin-mediated hepatic glucose uptake is impaired in type 2 diabetes: evidence for a relationship with glycemic control. , 2003, The Journal of clinical endocrinology and metabolism.

[27]  K. Polonsky,et al.  Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. , 1988, The New England journal of medicine.

[28]  V. Bolie,et al.  Coefficients of normal blood glucose regulation. , 1961, Journal of applied physiology.

[29]  R. DeFronzo,et al.  Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans. , 1989, The American journal of physiology.

[30]  F. Féry.  Role of hepatic glucose production and glucose uptake in the pathogenesis of fasting hyperglycemia in type 2 diabetes: normalization of glucose kinetics by short-term fasting. , 1994, The Journal of clinical endocrinology and metabolism.

[31]  R. Hovorka,et al.  Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes. , 2004, Physiological measurement.

[32]  L. Groop,et al.  Studies on the mass action effect of glucose in NIDDM and IDDM: evidence for glucose resistance , 1997, Diabetologia.

[33]  C Cobelli,et al.  Normal glucose-induced suppression of glucose production but impaired stimulation of glucose disposal in type 2 diabetes: evidence for a concentration-dependent defect in uptake. , 1998, Diabetes.

[34]  R. Gleason,et al.  A Model of Glucose-insulin Homeostasis in Man that Incorporates the Heterogeneous Fast Pool Theory of Pancreatic Insulin Release , 1978, Diabetes.

[35]  C Cobelli,et al.  Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans. , 1994, The Journal of clinical investigation.

[36]  Andrea Mari,et al.  Mathematical modeling in glucose metabolism and insulin secretion , 2002, Current opinion in clinical nutrition and metabolic care.

[37]  C. Cobelli,et al.  Effects of a change in the pattern of insulin delivery on carbohydrate tolerance in diabetic and nondiabetic humans in the presence of differing degrees of insulin resistance. , 1996, The Journal of clinical investigation.

[38]  L C Gatewood,et al.  Model studies of blood-glucose regulation. , 1965, The Bulletin of mathematical biophysics.

[39]  R. Bergman,et al.  Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. , 1981, The Journal of clinical investigation.

[40]  H D Landahl,et al.  Comparison of models of insulin release. , 1982, Bulletin of mathematical biology.

[41]  John Thomas Sorensen,et al.  A physiologic model of glucose metabolism in man and its use to design and assess improved insulin therapies for diabetes , 1985 .

[42]  L. Mandarino,et al.  Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus. , 1988, Metabolism: clinical and experimental.