Differences between HbA_1c and glucose-related variables in predicting weight loss and glycaemic changes in individuals with overweight and hyperglycaemia – The PREVIEW trial

Aims: To examine the differences between HbA_1c and glucose related variables in predicting weight loss and glycaemic changes following 8 weeks of low energy diet (LED) in individuals with overweight and hyperglycaemia. Research design and methods: 2178 individuals with ADA-defined pre-diabetes - impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) - who started an 8 week LED weight loss diet, were included in this analysis. Participants were enrolled in the PREVIEW (PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World) clinical trial. Multivariable linear mixed effects regression models and generalised additive mixed effect logistic models were used. Results: Only 1 in 3 participants (33%) had HbA_1c levels defined as pre-diabetes. Neither baseline HbA_1c, IFG or IGT were associated with body weight change at 8 weeks. Higher baseline body weight, baseline fasting insulin and weight loss predicted normalisation of fasting plasma glucose (FPG), whilst higher baseline fasting insulin, C-reactive protein (hsCRP) and older age predicted normalisation of HbA_1c. Additionally, male sex and higher baseline BMI, body fat and energy intake were positively associated with weight loss, whereas greater age and higher HDL-cholesterol predicted less weight loss. Conclusions: Whilst neither HbA_1c nor fasting glucose predicts short-term weight loss success, both may impact the metabolic response to rapid weight loss. We propose a role of inflammation versus total body adiposity since these variables are independent predictors of the normalisation of HbA_1c and fasting glucose, respectively.