Predicting pre-diabetes progression: a systematic review and meta-analysis.

Background: Pre-diabetes is a well-known risk factor for diabetes, a major contributor to morbidity and mortality globally. Identifying patients at highest risk of developing diabetes facilitates early intervention. There is no consensus on diagnostic criteria, with no single modality or range shown to be most predictive of progression to diabetes. Purpose: This systematic review and meta-analysis aimed to determine which single or combination biochemical test(s) and definition of pre-diabetes best predict progression to diabetes. Methods: Following primary screening of 11 980 papers from MEDLINE, Embase and Global Health, 40 original studies published between 2006 and 2024 looking at adults with pre-diabetes were included. Children, pregnant patient populations and groups with significant morbidity were excluded. Risk of bias was assessed with the JBI Critical Appraisal Checklist. Results: Our meta-analysis demonstrated the highest risk of progression to diabetes in the impaired fasting glucose (IFG) 6.1-6.9 mmol/L group, with an HR of 9.0 (4.6 to 13.5). Descriptive statistics identified the combination of IFG 6.1-6.9 mmol/L + impaired glucose tolerance + HbA1c 6.0%-6.4% had the highest percent incidence of diabetes per year, at 15.2%. Generally, combination tests were associated with higher progression rates. Conclusions: Certain single and combination biochemical test combinations may allow better identification of patients with pre-diabetes likely to progress to diabetes. To our knowledge, this is the first systematic review evaluating all testing combinations of these categories in progression and comparing pre-diabetes states as defined by multiple guidelines. This study (PROSPERO CRD42022312640) did not receive funding.