title: Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes.
abstract: A previous semi-mechanistic model described changes in fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) in patients with type 2 diabetic mellitus (T2DM) by modeling insulin sensitivity and β-cell function. It was later suggested that change in body weight could affect insulin sensitivity, which this study evaluated in a population model to describe the disease progression of T2DM. Nonlinear mixed effects modeling was performed on data from 181 obese patients with newly diagnosed T2DM managed with diet and exercise for 67 weeks. Baseline β-cell function and insulin sensitivity were 61% and 25% of normal, respectively. Management with diet and exercise (mean change in body weight = -4.1 kg) was associated with an increase of insulin sensitivity (30.1%) at the end of the study. Changes in insulin sensitivity were associated with a decrease of FPG (range, 7.8-7.3 mmol/L) and HbA1c (6.7-6.4%). Weight change as an effector on insulin sensitivity was successfully evaluated in a semi-mechanistic population model.
authors: Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden.
authors: S
authors: S
authors: Choy
authors: Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden.
authors: M C
authors: MC
authors: Kjellsson
authors: Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden.
authors: M O
authors: MO
authors: Karlsson
authors: Janssen Prevention Center Janssen Pharmaceutical Companies of Johnson & Johnson Leiden The Netherlands.
authors: W
authors: W
authors: de Winter
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000628:therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000378:metabolism; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human