Introduction: The effect of changes in body weight or insulin resistance on grey matter volume and cortical thickness change are unclear. The present observational study assessed effects of an 8-week weight loss period (≥8% of body weight), and a subsequent 22-month weight maintenance period on grey matter volume and cortical thickness.

Methods: A total of 24 participants (12f/12 m; age 52.8 ± 10.6 years) with overweight/obesity and pre-diabetes were recruited. T1-weighted magnetic resonance imaging was used to determine grey matter volume and cortical thickness at baseline, after the weight loss period and after a medium to high dietary protein weight maintenance period.

Results: At baseline, global grey matter volume was inversely associated with HOMA-IR, adjusted for sex and age (r = -0.42; p = .049). During the weight loss period participants decreased their BMI (32.1 ± 3.3 to 28.1 ± 2.8 kg/m2, p < .01), body-fat (41.6 ± 6.4 to 35.0 ± 8.0%, p < .01) and insulin resistance (HOMA-IR: 4.0 ± 2.0 to 1.8 ± 0.9, p < .01). During the 22-month weight maintenance period, these parameters gradually increased again (BMI: 29.3 ± 3.8 kg/m2; body-fat: 37.8 ± 9.3%; HOMA-IR: 2.9 ± 1.4, p < .01). Global grey matter volume and cortical thickness did not change significantly during the weight loss or weight maintenance period. Changes in body weight, body-fat percentage or insulin sensitivity were not associated with changes in global grey matter volume.

Conclusion: In conclusion, we confirmed that global grey brain matter volume was inversely associated with insulin resistance at baseline, yet an intervention yielding a decrease in insulin resistance did not lead to changes in global grey brain matter volume or cortical thickness.

Trial registration: The trial is registered with ClinicalTrials.gov, NCT01777893.