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

AIMS/HYPOTHESIS: 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 HbA1c-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. METHODS: 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 HbA1c [6.0-6.4%/42-46 mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models. RESULTS: Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA1c, 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. CONCLUSIONS/INTERPRETATION: This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA1c 6.0-6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.