Introduction: Gout, the most common form of inflammatory arthritis in men, is caused by monosodium urate crystal deposition in joints and soft tissues . Gout and diabetes are highly prevalent metabolic conditions which often co-exist due to the shared risk factors including obesity, hypertension, hyperlipidaemia and impaired kidney function . Both gout and diabetes are associated with major functional and structural lower limb and foot impairments. People with gout report high levels of foot pain and disability, exhibit altered gait patterns and commonly present with tophus deposition in structures surrounding the foot and ankle [3, 4]. Individuals with diabetes also present with foot problems related to mobility loss, foot ulceration and impaired gait . Efficient function of lower limb muscles is central to the function of the foot and ankle and the ability to carry out normal activities of daily living including standing, walking and ascending and descending stairs. Reduced strength of muscles surrounding the foot and ankle has been previously demonstrated in individuals with gout  and diabetes . However, it is unclear whether people with both conditions exhibit a greater reduction in strength compared to those with either diabetes or gout, or neither.
Objective: To determine the differences in foot and ankle muscle strength between people with gout, diabetes, both gout and diabetes and age- and sex-matched controls.
Methods: In total, 112 participants were recruited, including 35 participants with gout, 28 with diabetes, 20 with both gout and diabetes, and 29 age- and sex-matched controls. Participants were recruited from a rheumatology department at Counties Manukau District Health Board, Auckland, New Zealand, together with an age- and sex-matched control population from public advertising at Auckland University of Technology (AUT). Participants with gout met the 1977 preliminary American Rheumatism Association classification criteria for gout. Diagnosis of diabetes was self-reported and confirmed through hospital records. The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614001140640). Age, gender, ethnicity, body mass index (BMI), current medications and co-morbidities were recorded for all participants. Additionally, blood chemistry was assessed to determine the presence of kidney disease including serum creatinine and estimated glomerular filtration rate. In addition, gout disease duration, serum urate and the presence of subcutaneous tophi, were recorded for the participants with gout. The most recent HbA1C were recorded for the participants with diabetes. General body pain and patient global over the past week were assessed using 100mm Visual Analog Scales (VAS). The Health Assessment Questionnaire - Disability Index (HAQ-DI) was used to measure activity limitation in the past week . Patient-specific reported foot pain and disability was assessed using the Manchester Foot Pain and Disability Index (MFPDI) . Sensory testing, via vibration perception threshold was assessed over the medial aspect of the first metatarsophalangeal joint using a biothesiometer. Isometric muscle force for foot and ankle plantarflexion, dorsiflexion, inversion and eversion was measured using hand-held dynamometry. To determine whether participant demographics were different between the four groups, one-way ANOVAs (for continuous data) and Kruskal-Wallis tests (for categorical data) were used. To determine whether there were significant differences between the participant groups for each muscle test condition, mixed linear models were used. All models were adjusted for age, sex and BMI. Models accounted for repeated measures taken from right and left feet of each participant through adopting a mixed models approach in which a participant-specific random effect and participant-nested random effect for foot-side were included.
Results: Participants with gout and/or diabetes had greater body mass index (BMI) and more frequent hypertension, hyperlipidaemia and chronic kidney disease, compared to control participants (p<0.001). After adjusting for age, sex and BMI, participants with gout (p<0.001), diabetes (p<0.001), and both gout and diabetes (p<0.001) had reduced plantarflexion strength compared to controls. Additionally, participants with diabetes had reduced plantarflexion strength compared to participants with gout (p=0.045). Participants with gout (p<0.001), diabetes (p<0.001) and both gout and diabetes (p<0.001) had reduced dorsiflexion and inversion strength compared to the control group. Participants with gout (p=0.003), diabetes (p<0.001), and both conditions (p=0.001) also demonstrated reduced eversion strength compared to the control group. Conclusions: Patients with gout, diabetes and co-existing gout and diabetes have impaired muscle strength in foot and ankle plantarflexion, dorsiflexion, eversion and inversion. Patients with concomitant disease do not exhibit differences in foot and ankle muscle strength compared to individuals with gout only or diabetes only. The reduction in foot and ankle muscle strength observed in people with gout demonstrates similarities with previous research in which concentric muscle strength was measured using isokinetic dynamometry . The exact mechanism responsible for muscle weakness in gout is not well understood, but may be attributed to a combination of factors, including local tophus deposition , disuse muscle atrophy due to pain-avoidance gait mechanisms , or neural arthrogenic inhibition  secondary to the joint damage and persistent inflammation characteristic of gouty arthritis . These data highlight the importance of foot and ankle strengthening exercises in individuals with chronic foot conditions to prevent or reduce lower limb disability. Significance: Patients with gout, diabetes and both gout and diabetes exhibit reduced foot and ankle muscle strength when compared to individuals with neither condition. Foot and ankle muscle strength in patients with coexisting gout and diabetes does not differ from patients with either condition alone. This study highlights the need for future research assessing the benefits of foot and ankle strengthening exercises to improve lower limb function in people with chronic comorbid conditions.
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