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J Appl Physiol (1985). 2018 Aug 1;125(2):553-566. doi: 10.1152/japplphysiol.00160.2018. Epub 2018 Mar 29.

Mechanisms for the increased fatigability of the lower limb in people with type 2 diabetes.

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Program in Exercise Science, Department of Physical Therapy, Marquette University , Milwaukee, Wisconsin.
Division of Endocrinology, Metabolism, and Clinical Nutrition, Department of Medicine, Medical College of Wisconsin , Milwaukee, Wisconsin.
Department of Clinical Laboratory Science, Marquette University , Milwaukee, Wisconsin.
Musculoskeletal Health Research Group, Faculty of Health Sciences, The University of Sydney, Lidcombe, New South Wales , Australia.


Fatiguing exercise is the basis of exercise training and a cornerstone of management of type 2 diabetes mellitus (T2D); however, little is known about the fatigability of limb muscles and the involved mechanisms in people with T2D. The purpose of this study was to compare fatigability of knee extensor muscles between people with T2D and controls without diabetes and determine the neural and muscular mechanisms for a dynamic fatiguing task. Seventeen people with T2D [ten men and seven women: 59.6 (9.0) yr] and twenty-one age-, body mass index-, and physical activity-matched controls [eleven men and ten women: 59.5 (9.6) yr] performed one hundred twenty high-velocity concentric contractions (one contraction/3 s) with a load equivalent to 20% maximal voluntary isometric contraction (MVIC) torque with the knee extensors. Transcranial magnetic stimulation (TMS) and electrical stimulation of the quadriceps were used to assess voluntary activation and contractile properties. People with T2D had larger reductions than controls in power during the fatiguing task [42.8 (24.2) vs. 26.4 (15.0)%; P < 0.001] and MVIC torque after the fatiguing task [37.6 (18.2) vs. 26.4 (12.1)%; P = 0.04]. People with T2D had greater reductions than controls in the electrically evoked twitch amplitude after the fatiguing task [44.0 (20.4) vs. 35.4 (12.1)%, respectively; P = 0.01]. However, the decrease in voluntary activation was similar between groups when assessed with electrical stimulation [12.1 (2.6) vs. 12.4 (4.4)% decrease; P = 0.84] and TMS ( P = 0.995). A greater decline in MVIC torque was associated with larger reductions of twitch amplitude ( r2 = 0.364, P = 0.002). Although neural mechanisms contributed to fatigability, contractile mechanisms were responsible for the greater knee extensor fatigability in men and women with T2D compared with healthy controls. NEW & NOTEWORTHY Transcranial magnetic stimulation and percutaneous muscle stimulation were used to determine the contributions of neural and contractile mechanisms of fatigability of the knee extensor muscles after a dynamic fatiguing task in men and women with type 2 diabetes (T2D) and healthy age-, body mass index-, and physical activity-matched controls. Although neural and contractile mechanisms contributed to greater fatigability of people with T2D, fatigability was primarily associated with impaired contractile mechanisms and glycemic control.


diabetes mellitus; knee extensors; muscle fatigue; sex differences; skeletal muscle

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