Progression rates from HbA1c 6.0-6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis

Precise estimates of progression rates from 'prediabetes' to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals. There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA(1c)-defined prediabetes ranges, with some favouring 6.0-6.4% (42-46 mmol/mol). Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories. Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5.6-6.9 mmol/l], WHO-defined IFG [6.1-6.9 mmol/l], IGT (7.8-11.0 mmol/l) or raised HbA(1c) [6.0-6.4%/42-46 mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models. Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA(1c), the pooled incidence rate (95% credible interval) of diabetes was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5 [37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results were seen when the data were analysed by the criteria used to diagnose diabetes. This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA(1c) 6.0-6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.