Dataset Information

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.

SUBMITTER: Zaharia OP

PROVIDER: S-EPMC7993587 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivePrior genome-wide association and exon array expression studies both provided suggestive evidence that apoptosis signal regulating kinase 1 (ASK1) may influence in vivo insulin action in Pima Indians. Genetic variants in or near ASK1 were analyzed to assess the role of this gene in insulin action and type 2 diabetes.Research design and methodsGenotypic data from 31 variants were used to determine the linkage disequilibrium pattern across ASK1 in Pima Indians. Eight tag SNPs were initially genotyped in 3,501 full-heritage Pima Indians. Replication for association with diabetes was assessed in a second population-based sample of 3,723 Native Americans and the published DIAGRAM study. Quantitative traits were analyzed in 536 nondiabetic Native Americans, and ASK1 expression was examined in skeletal muscle of 153 nondiabetic Native Americans.ResultsThree tag SNPs were associated with type 2 diabetes (rs35898099, P = 0.003, odds ratio [95% CI] 1.27 [1.08-1.47]; rs1570056, P = 0.007, 1.19 [1.05-1.36]; rs7775356, P = 0.04, 1.14 [1.01-1.28]) in the full-heritage Pima Indians. The association with rs35898099 was replicated in a second sample of Native Americans (P = 0.04, 1.22 [1.01-1.47]), while that for rs1570056 was replicated in the DIAGRAM study of Caucasians (Z statistic based P = 0.026; fixed-effect model, 1.06 [1.00-1.12]). The diabetes risk allele for rs1570056 was associated with reduced insulin action as assessed by either HOMA-IR in 2,549 nondiabetic full-heritage Pima Indians (P = 0.027) or a hyperinsulinemic-euglycemic clamp among 536 nondiabetic Native Americans (P = 0.02). Real-time PCR identified a positive correlation between ASK1 expression in skeletal muscle biopsies and in vivo insulin action (P = 0.02, r = 0.23), and the risk allele for rs1570056 was associated with lower ASK1 expression (P = 0.003, r = -0.22).ConclusionsASK1 variants may increase susceptibility to type 2 diabetes by decreasing insulin sensitivity via reduced ASK1 expression.