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Randomized Controlled Trial
. 2025 Mar 27;192(4):456-465.
doi: 10.1093/ejendo/lvaf004.

High-intensity interval training improves insulin sensitivity in individuals with prediabetes

Pernille Mensberg  1   2 , Clarissa Frandsen  1   2 , Christian S Carl  3 , Emilie Espersen  1   2 , Thomas Leineweber  1   2 , Emil L Larsen  1   2   4 , Heidi Storgaard  1   2 , Kirstine Schlawitz  5 , Torben H D Petersen  5 , Jytte N Poulsen  5 , Frederik Sørensen  6 , Peter M Gørtz  7 , Julie L Forman  6 , Bente Kiens  3 , Filip K Knop  1   2   8   9 , Tina Vilsbøll  1   2   8
Affiliations
Randomized Controlled Trial

High-intensity interval training improves insulin sensitivity in individuals with prediabetes

Pernille Mensberg et al. Eur J Endocrinol. .

Abstract

Objective: To examine the separate and combined effects of low-volume high-intensity interval training (HIIT) and walking compared with no training on insulin sensitivity and skeletal metabolic capacity in individuals with prediabetes.

Design: Individuals were randomized to: (1) control (no exercise), (2) HIIT (3 × 20 s's cycle sprint 3 times weekly), (3) HIIT + walking (walking >10 000 steps/day), or (4) walking for 12 weeks.

Methods: Insulin sensitivity was assessed by an oral glucose tolerance test at baseline and end-of-trial. Additionally, proteins important for mitochondria capacity and insulin sensitivity were measured in the vastus lateralis muscle.

Results: Seventy sedentary individuals with prediabetes (women n = 36; age: 60.8 ± 11.3 years (mean ± SD); body mass index: 31.6 ± 4.4 kg/m2; fasting plasma glucose: 6.6 ± 0.8 mmol/L; glycated hemoglobin A1c 5.7 ± 0.4% (39.0 ± 4.3 mmol/mol) were included. Compared with control, peripheral insulin sensitivity (measured by the Cederholm index) was significantly improved with HIIT (estimated treatment difference [ETD]: 18.5% [95% confidence interval (CI): 7.4; 28.3%] and HIIT + walking [ETD: 15.7% (95% CI: 4.4; 25.6%)]), but not with walking alone (ETD: 9.4% [95% CI: -2.5; 19.9%]). Whole-body insulin sensitivity (measured by the Matsuda index) was significantly increased with HIIT + walking (ETD: 28.0% [95% CI: 10.3; 42.3%]) and walking alone (ETD: 42.3% [95% CI: 28.3; 53.5%]), but not with HIIT alone (ETD: 17.0% [95% CI: -4.0; 33.7%]). Protein expression of proteins involved in mitochondrial capacity in skeletal muscle and glucose uptake were most improved with HIIT + walking, and no significant effects were observed with walking alone.

Conclusions: Twelve weeks of low-volume HIIT training can improve glucose control and induces adaptations in skeletal muscle important for metabolic health in individuals with prediabetes.

Keywords: HIIT; exercise; insulin sensitivity; mitochondrial function; prediabetes.

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Conflict of interest statement

Conflict of interest: P.M., C.F., C.S.C., E.E., T.L., H.S., T.H.D.P., J.N.P., F.S., P.M.G., J.L.F., B.K., and have no relevant disclosures. F.K.K. has served on scientific advisory panels, has been part of speaker's bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, Lupin, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi, and Zealand Pharma, and is a minority shareholder in Antag Therapeutics ApS and is currently employed at Novo Nordisk A/S, Søborg, Denmark. T.V. declares personal fees from Amgen, Boehringer Ingelheim, Eli Lilly, AstraZeneca, GSK, Roche, Sanofi, Sun Pharmaceuticals, Novo Nordisk, Zealand Phama, and Bristol Myers Squibb, and grants (to her institution) from Eli Lilly. E.L.L. has received research funding for an unrelated investigator-initiated study from Boehringer Ingelheim.

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