# Optimal exercise dose for glycemic control in prediabetes across different exercise types PMID: 41377666 Journal: iScience Published: 2025-11-10 Authors: Yan R, Li Y, Jia S, He J, Lin G, Huang W, Sun J, Li D ## Question Which exercise modality and weekly exercise dose best reduces HbA1c in adults with prediabetes, and how do baseline BMI and exercise type modify minimum effective and optimal doses? ## Summary This systematic review and Bayesian network and dose-response meta-analysis of 39 randomized trials in adults with prediabetes found that exercise interventions reduced HbA1c compared with control conditions. HIIT had the largest estimated HbA1c reduction and reached a clinically meaningful dose threshold at 350 METs.min/week, but the certainty for HIIT was very low, so the true effect remains uncertain. ## Population - Adults with prediabetes included in 39 randomized controlled trials. - Sample size: 3421 - Age: Mean 55.82 years. - Sex: 45.9% male. - Health status: Prediabetes; mean BMI 26.85. ## Methodology - Systematic review with pairwise meta-analysis, Bayesian network meta-analysis, Bayesian dose-response meta-analysis, meta-regression, sensitivity analyses, risk-of-bias assessment, and CINeMA certainty assessment. - Included exercise-only randomized controlled trials with at least 4 weeks of intervention; individual study durations varied. - Published randomized trials from six databases across 12 countries; exercise settings varied by included study. - Randomized and controlled study design. ## Protocol - Exercise interventions including HIIT. - Modality: Multiple exercise modalities across included RCTs. - Intensity: Weekly dose quantified as METs.min/week using 2024 Adult Compendium values; HIIT category minimum clinically meaningful dose 350 METs.min/week and optimal dose 850 METs.min/week. - Program length: At least 4 weeks in included RCTs. - Progression: Progressive prescriptions were averaged for dose estimation. - Usual care, wait-list, health education, or alternative exercise modality. - Modality: Varied. ## Outcomes ### HbA1c, network meta-analysis Status: improved All exercise modalities reduced HbA1c compared with usual care; HIIT had the largest estimated effect but very low certainty. HIIT MD -0.50%, 95% CrI -0.62 to -0.36, SUCRA 99%; CT MD -0.34%, AT MD -0.28%, RT MD -0.28%, MBT MD -0.21%. ### HbA1c, pairwise meta-analysis Status: improved HIIT significantly reduced HbA1c compared with controls in direct pairwise analysis. HIIT MD -0.78%, 95% CI -1.16 to -0.40; CT -0.36%, AT -0.28%, RT -0.30%, MBT -0.19%. ### Dose-response relationship Status: mixed A nonlinear J-shaped dose-response was observed, with estimated overall optimal dose of 850 METs.min/week. After BMI adjustment at 850 METs.min/week: obesity MD -0.339%, 95% CrI -0.440 to -0.238; normal weight and overweight statistically significant but not clinically meaningful by MCID. ### HIIT dose-response Status: improved HIIT produced clinically meaningful reductions at lower dose than other modalities in unadjusted modality analysis. HIIT minimum dose 350 METs.min/week, MCFB -0.306%, 95% CrI -0.371 to -0.240; optimal dose 850 METs.min/week, MCFB -0.52%, 95% CrI -0.598 to -0.443. ### Adherence Status: no clear change No statistically significant adherence differences were found between exercise interventions and control. HIIT OR 0.91, 95% CrI 0.15 to 5.1; CT OR 2.5, 95% CrI 0.49 to 13; RT OR 2.2, AT OR 1.6, MBT OR 1.1. ### Adverse events Status: mixed Reported events were low-incidence and mostly mild to moderate, but HIIT had seven reported events among 94 participants in two studies. AT: 4 events/135 participants; HIIT: 7 events/94 participants; RT: 3 events/42 participants among studies reporting events. ## Practical Insights - HIIT may be promising for HbA1c reduction in prediabetes, but the certainty is very low and should be communicated cautiously. - For glycemic-control programming, weekly dose may need to account for MET intensity, duration, frequency, and BMI rather than minutes alone. - The review supports content about an overall estimated optimum around 850 METs.min/week, while noting that exact workout structures are not specified. - Safety messaging should reflect limited adverse-event reporting and the clinical nature of prediabetes populations. ## Limitations - 79.5% of included studies were conducted in Asian populations, limiting global generalizability. - Dose was estimated using standardized MET compendium values rather than individual objective energy expenditure. - Limited evidence for BMI >=32 kg/m2. - HIIT evidence had very low certainty and local inconsistency in some comparisons. - Protocol-level work-rest details for HIIT were not available in the main article. ## Safety And Adherence - AT reported four adverse events across three studies among 135 participants: sprain, cardiovascular event, fall, and hypoglycaemia. - HIIT reported seven adverse events across two studies among 94 participants: six soft tissue injuries, one cardiovascular event, and one knee pain case. - RT reported three adverse events in one study among 42 participants: two muscle strains and one hypoglycaemia case. - Authors characterized reported adverse events as primarily mild to moderate with low incidence. ## Original Sources - [PubMed](https://pubmed.ncbi.nlm.nih.gov/41377666/) (pubmed) - [DOI](https://doi.org/10.1016/j.isci.2025.113980) (doi) - [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12689185/) (full text) ## Agent Guidance Preserve the paper-level scope of this note. Do not generalize beyond the population, protocol, measured outcomes, and limitations above.