Modelling the effect of very low calorie diet on weight and fasting plasma glucose in obese type 2 diabetic patients
(English)Manuscript (preprint) (Other academic)
Background: Change in weight (WT) as a result of diet changes is closely associated with change in fasting plasma glucose (FPG) in type 2 diabetes mellitus (T2DM) patients. Two hypotheses on this relationship are 1) weight loss induces a change in an intermediary effector that reduces FPG, with the intermediary effector being insulin sensitivity (IS) or 2) an underlying change of the system affects weight as well as FPG. The aim of this study was to test these hypotheses using non-linear mixed effects modelling on summary level data from publications of weight loss with very low calorie diets (VLCD).
Methods: Summary level data was gathered from 8 clinical studies of diabetic patients (n=167 from 12 arms) treated with VLCD where weight and FPG was measured. The patients had a baseline weight ranging from 93-118 kg, and baseline FPG ranging from 91-321 mg/dL, treated with VLCD for up to 224 days. Non-linear mixed-effects modelling was performed using NONMEM 7.2.
Results: Both weight and FPG was modelled using indirect response models, with VLCD implemented as an instantaneous inhibitory effect on the input. The objective function value for the model describing hypothesis 2 was significantly lower than for hypothesis 1. The VLCD diet was estimated to reduce 42% of the Kin of weight and 51% of the Kin of FPG. Baseline BMI was a significant covariate effect on the scaling factor for the effect on FPG.
Conclusions: The model with an underlying mechanism that affects both weight and FPG was found to better describe the data than using weight loss as an effector on a mediator through which FPG is reduced.
Body weight, fasting plasma glucose, type 2 diabetes, very low calorie diet, modelling, weight loss, meta-analysis
Endocrinology and Diabetes
Research subject Pharmaceutical Science
IdentifiersURN: urn:nbn:se:uu:diva-272229OAI: oai:DiVA.org:uu-272229DiVA: diva2:893558