Type 1 diabetes (T1D) is associated with reduced muscular strength and greater muscle fatigability. Along with changes in muscular mechanisms, T1D is also linked to structural changes in the brain. How the neurophysiological mechanisms underlying muscle fatigue is altered with T1D and sex related differences of these mechanisms are still not well investigated. The aim of this study was to determine the impact of T1D on the neural correlates of handgrip fatigue and examine sex and T1D related differences in neuromuscular performance parameters, neural activation and functional connectivity patterns between the motor regions of the brain. Forty-two adults, balanced by condition (healthy vs T1D) and sex (male vs female), and performed submaximal isometric handgrip contractions until voluntary exhaustion. Initial strength, endurance time, strength loss, force variability, and complexity measures were collected. Additionally, hemodynamic responses from motor-function related cortical regions, using functional near-infrared spectroscopy (fNIRS), were obtained. Overall, females exhibited lower initial strength (p < 0.0001), and greater strength loss (p = 0.023) than males. While initial strength was significantly lower in the T1D group (p = 0.012) compared to the healthy group, endurance times and strength loss were comparable between the two groups. Force complexity, measured as approximate entropy, was found to be lower throughout the experiment for the T1D group (p = 0.0378), indicating lower online motor adaptability. Although, T1D and healthy groups fatigued similarly, only the T1D group exhibited increased neural activation in the left (p = 0.095) and right (p = 0.072) supplementary motor areas (SMA) over time. A sex × condition × fatigue interaction effect (p = 0.044) showed that while increased activation was observed in both T1D females and healthy males from the Early to Middle phase, this was not observed in healthy females or T1D males. These findings demonstrate that T1D adults had lower adaptability to fatigue which they compensated for by increasing neural effort. This study highlights the importance of examining both neural and motor performance signatures when investigating the impact of chronic conditions on neuromuscular fatigue. Additionally, the findings have implications for developing intervention strategies for training, rehabilitation, and ergonomics considerations for individuals with chronic conditions.

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