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

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.

© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.

Musculoskeletal function. Parameters of musculoskeletal function in individuals with normal glucose tolerance and no osteoarthritis (CON-OA, circles), with osteoarthritis (CON+OA, squares), patients with type 2 diabetes without osteoarthritis (T2D-OA, triangles), and with osteoarthritis (T2D+OA, inverted triangles) showing osteoarthritis-related symptoms quantified by the A, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score; B, sensorimotor abilities; C, stability; D, knee extension strength; E, grip strength; and F, knee range of motion. Data shown as individual values and bars for mean and SD. P values refer to comparison of data adjusted for age, sex, and body mass index. Data were ln-transformed where applicable. *P less than or equal to .05.

Figure 2.

Parameters of nerve function and bone mineral density. Parameters of nerve and bone function in individuals with normal glucose tolerance and no osteoarthritis (CON-OA, circles), with osteoarthritis (CON+OA, squares), patients with type 2 diabetes without osteoarthritis (T2D-OA, triangles), and with osteoarthritis (T2D+OA, inverted triangles) showing nerve conduction velocity in the A, peroneus nerve, and the B, median nerve; C, bone mineral density in the lumbar spine; and D, the femoral neck. Dotted red lines correspond to the World Health Organization criteria for osteoporosis (T-score  −1 SD). *P less than or equal to .05.

Figure 3.

Biomarkers of adipose tissue function and inflammation. A, Adiponectin; B, tumor necrosis factor α (TNF)α; C, interleukin (IL)-6; D, IL-1 receptor antagonist (ra); and E, leptin levels in individuals with normal glucose tolerance and no osteoarthritis (CON-OA, circles), with osteoarthritis (CON+OA, squares), patients with type 2 diabetes without osteoarthritis (T2D-OA, triangles), and with osteoarthritis (T2D+OA, inverted triangles). Correlation analyses (Spearman correlation coefficient r and respective P value) between biomarkers of inflammation (leptin and IL-1ra) and F, glycemic control (glycated hemoglobin [HbA1c]); G, muscle strength; as well as H, symptom severity (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] score). *P less than or equal to .05 adjusted for age, sex, and body mass index.

Figure 4.

microRNA expression levels. Differences in microRNA expression levels between individuals with normal glucose tolerance (CON) and patients with type 2 diabetes (T2D) are depicted as a volcano plot with statistically significant different microRNAs marked as A, green circles showing a tendency for upregulation in patients with type 2 diabetes. Further stratification of the top 15 statistically different microRNAs is presented in a heat map for individuals with normal glucose tolerance without osteoarthritis (CON-OA), with osteoarthritis (CON+OA), patients with type 2 diabetes without osteoarthritis (T2D-OA), and with osteoarthritis (T2D+OA). Differences in microRNA expression levels between individuals with osteoarthritis (+OA) and patients without osteoarthritis (-OA) are depicted as volcano plot with statistically significant different microRNAs marked as B, green circles showing a tendency for downregulation in individuals with normal glucose tolerance without osteoarthritis. Further stratification of the top 15 statistically different microRNAs is presented in a heat map for individuals with normal glucose tolerance without osteoarthritis (CON-OA), with osteoarthritis (CON+OA), patients with type 2 diabetes without osteoarthritis (T2D-OA), and with osteoarthritis (T2D+OA). Green shades depict upregulation, whereas yellow shades depict downregulation.