Modeling of 24-Hour Glucose and Insulin Profiles of Patients With Type 2 Diabetes

被引：38
作者：
Jauslin, Petra M. [1 ,2 ]
Frey, Nicolas
Karlsson, Mats O. [2 ]
机构：
[1] F Hoffmann La Roche Ltd, Dept Biomath, Modeling & Simulat Grp, Biomath Modeling & Simulat,PDIM M,Biomath, CH-4070 Basel, Switzerland
[2] Uppsala Univ, Dept Pharmaceut Biosci, Div Pharmacokinet & Drug Therapy, S-75105 Uppsala, Sweden
来源：
JOURNAL OF CLINICAL PHARMACOLOGY | 2011年 / 51卷 / 02期
关键词：
NONMEM; glucose homeostasis; type; 2; diabetes; meal test; circadian rhythm;
D O I：
10.1177/0091270010362536
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
A model able to simultaneously characterize and simulate 24-hour glucose and insulin profiles following multiple meal tests was developed, extending an integrated glucose-insulin model for oral glucose tolerance tests that was previously published. The analysis was based on glucose and insulin measurements from 59 placebo-treated patients with type 2 diabetes. Circadian variations in glucose homeostasis were assessed on relevant parameters based on literature review. They were best described by a nighttime dip in insulin secretion between approximately 9 p.m. and 5 a.m. using a modulator function. The integrated glucose-insulin model has thus been shown to be applicable to real-life situations determined by multiple meals over the course of a day. This provides the basis for the analysis and simulation of long-term glucose and insulin data. The model may also prove useful for understanding antidiabetic drug actions and requirements in the context of circadian changes in glucose-insulin regulation.
引用
收藏
页码：153 / 164
页数：12
相关论文
共 46 条
  • [1] Marshall S., MacIntyre F., James I., Krams M., Jonsson N.E., Role of mechanistically-based pharmacokinetic/pharmacodynamic models in drug development : A case study of a therapeutic protein, Clin Pharmacokinet, 45, pp. 177-197, (2006)
  • [2] Jonsson E.N., MacIntyre F., James I., Krams M., Marshall S., Bridging the pharmacokinetics and pharmacodynamics of UK-279,276 across healthy volunteers and stroke patients using a mechanistically based model for target-mediated disposition, Pharm Res, 22, pp. 1236-1246, (2005)
  • [3] Silber H.E., Jauslin P.M., Frey N., Gieschke R., Simonsson U.S., Karlsson M.O., An integrated model for glucose and insulin regulation in healthy volunteers and type 2 diabetic patients following intravenous glucose provocations, J Clin Pharmacol, 47, pp. 1159-1171, (2007)
  • [4] Jauslin P., Silber H.E., Frey N., An integrated glucose-insulin model to describe oral glucose tolerance test data in type 2 diabetics, J Clin Pharmacol, 47, pp. 1244-1255, (2007)
  • [5] Boden G., Chen X., Urbain J.L., Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production, Diabetes, 45, pp. 1044-1050, (1996)
  • [6] Shapiro E.T., Polonsky K.S., Copinschi G., Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes, J Clin Endocrinol Metab, 72, pp. 444-454, (1991)
  • [7] Yki-Jarvinen H., Helve E., Sane T., Nurjhan N., Taskinen M.R., Insulin inhibition of overnight glucose production and gluconeogenesis from lactate in NIDDM, Am J Physiol, 256, (1989)
  • [8] Beebe C.A., Van Cauter E., Shapiro E.T., Effect of temporal distribution of calories on diurnal patterns of glucose levels and insulin secretion in NIDDM, Diabetes Care, 13, pp. 748-755, (1990)
  • [9] Carroll M.F., Schade D.S., The dawn phenomenon revisited: Implications for diabetes therapy, Endocr Pract, 11, pp. 55-64, (2005)
  • [10] Bergman R., Ider Y.Z., Bowden C.R., Cobelli C., Quantitative estimation of insulin sensitivity, Am J Physiol, 236, (1979)
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