Reduced Muscle Strength Is Associated With Insulin Resistance in Type 2 Diabetes Patients With Osteoarthritis

J Clin Endocrinol Metab. 2021 Mar 25;106(4):1062-1073. doi: 10.1210/clinem/dgaa912.

Abstract

Context: Type 2 diabetes is associated with a greater risk for musculoskeletal disorders, yet its impact on joint function remains unclear.

Objective: We hypothesized that patients with type 2 diabetes and osteoarthritis would exhibit musculoskeletal impairment, which would associate with insulin resistance and distinct microRNA profiles.

Methods: Participants of the German Diabetes Study with type 2 diabetes (T2D, n = 39) or normal glucose tolerance (CON, n = 27), both with (+OA) or without osteoarthritis (-OA) underwent intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp tests. Musculoskeletal function was assessed by isometric knee extension strength (KES), grip strength, range of motion (ROM), and balance skills, while neural function was measured by nerve conductance velocity (NCV). Arthritis-related symptoms were quantified using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, serum arthritis-related microRNA using quantitative polymerase chain reaction.

Results: Insulin sensitivity was lower in T2D+OA vs T2D-OA (4.4 ± 2.0 vs 5.7 ± 3.0 mg* kg-1*min-1) and in CON+OA vs CON-OA (8.1 ± 2.0 vs 12.0 ± 2.6 mg*kg-1,*min-1, both P < .05). In T2D+OA, KES and ROM were 60% and 22% lower than in CON+OA, respectively (both P < .05). Insulin sensitivity correlated positively with KES (r = 0.41, P < .05) among T2D, and negatively with symptom severity in CON and T2D (r = -0.60 and r = -0.46, respectively, P < .05). CON+OA and T2D+OA had inferior balance skills than CON-OA, whereas NCV was comparable in T2D+OA and T2D-OA. Expression of arthritis-related microRNAs was upregulated in T2D compared to CON, but downregulated in CON+OA compared to CON-OA (P < .05), and did not differ between T2D+OA and T2D-OA.

Conclusion: Musculoskeletal impairment and osteoarthritis-related symptoms are associated with insulin resistance. Type 2 diabetes can mask changes in arthritis-related microRNA profiles.

Trial registration: ClinicalTrials.gov NCT01055093.

Keywords: insulin secretion; insulin sensitivity; muscle strength; osteoarthritis; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Germany
  • Glucose Clamp Technique
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Muscle Strength / physiology
  • Muscle Weakness / etiology*
  • Muscle Weakness / metabolism
  • Muscle Weakness / physiopathology
  • Osteoarthritis / complications*
  • Osteoarthritis / metabolism
  • Osteoarthritis / physiopathology
  • Osteoarthritis, Knee / complications
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / physiopathology
  • Surveys and Questionnaires

Substances

  • Insulin

Associated data

  • ClinicalTrials.gov/NCT01055093