Responses to lifestyle interventions among individuals with distinct pre-diabetes phenotypes: A systematic review and Meta-Analysis

Aims: To assess responses to lifestyle interventions (LIs) among individuals with distinct pre-diabetes phenotypes (isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT], and combined IFG + IGT) for reducing diabetes incidence, reversing pre-diabetes, and improving glycemic control and insulin sensitivity.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched until December 6th, 2023. We included randomized controlled trials examining responses to LIs (including diet and/or physical activity) among adults with i-IFG, i-IGT, and IFG + IGT. Outcomes included diabetes incidence, normoglycemia incidence, fasting plasma glucose (FPG), 2-hour plasma glucose (2 h-PG), hemoglobin A1c, fasting insulin (FI), and homeostasis model assessment-insulin resistance (HOMA-IR). Random-effects meta-analyses were performed to estimate risk ratios (RRs) and mean differences.

Results: Twenty-seven studies were included. Meta-analysis of 10 studies that performed stratified analyses by pre-diabetes phenotype found that LIs significantly reduced diabetes incidence in i-IGT (RR = 0.69 [0.56; 0.85], I² = 14 %) and IFG + IGT (RR = 0.56 [0.48; 0.66], I² = 0 %) but not in i-IFG (RR = 0.85 [0.66; 1.11], I² = 0 %; p_subgroup = 0.02). Meta-analysis of 20 studies using IGT for participant recruitment showed that LIs significantly decreased diabetes incidence, increased normoglycemia incidence, and improved FPG, 2 h-PG, FI and HOMA-IR.

Conclusions: LIs are effective for IGT (with or without IFG), but tailored LIs are needed for i-IFG to prevent diabetes.