title: Estimating the predictive validity of diabetic animal models in rosiglitazone studies.
abstract: For therapeutic studies, predictive validity of animal models - arguably the most important feature of animal models in terms of human relevance - can be calculated retrospectively by obtaining data on treatment efficacy from human and animal trials. Using rosiglitazone as a case study, we aim to determine the predictive validity of animal models of diabetes, by analysing which models perform most similarly to humans during rosiglitazone treatment in terms of changes in standard diabetes diagnosis parameters (glycosylated haemoglobin [HbA1c] and fasting glucose levels). A further objective of this paper was to explore the impact of four covariates on the predictive capacity: (i) diabetes induction method; (ii) drug administration route; (iii) sex of animals and (iv) diet during the experiments. Despite the variable consistency of animal species-based models with the human reference for glucose and HbA1c treatment effects, our results show that glucose and HbA1c treatment effects in rats agreed better with the expected values based on human data than in other species. Induction method was also found to be a substantial factor affecting animal model performance. The study concluded that regular reassessment of animal models can help to identify human relevance of each model and adapt research design for actual research goals.
authors: Laboratory Animal Science group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.|Department of Preventive Medicine, Faculty of Public Health, University of Debrecen, Debrecen, Hungary.
authors: O E
authors: OE
authors: Varga
authors: 1st Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: N
authors: N
authors: Zsíros
authors: Laboratory Animal Science group, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors: I A S
authors: IA
authors: Olsson
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D000077154:Rosiglitazone; D012727:Sex Characteristics; D013045:Species Specificity; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077154:Rosiglitazone; D045162:Thiazolidinediones
keywords: Animal models; human relevance; predictive validity; type 2 diabetes