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Study Demonstrates Link Between Rheumatoid Arthritis and Insulin Resistance

Rheumatoid arthritis and diabetes may be closely related, according to researchers writing in the June issue of Arthritis and Rheumatology.

Rheumatoid arthritis and diabetes may be closely related, according to researchers writing in the June issue of Arthritis and Rheumatology.

Led by Ronan H. Mullan, MBCHB, Ph.D., of Trinity Centre for Health Science, Ireland, researchers conducted a study of 92 rheumatoid arthritis and osteoarthritis patients finding that insulin resistance was independently associated with a high body mass index (61 patients) and swollen joint count in 28 joints (61 patients).

“Both type 2 diabetes mellitus and chronic inflammatory diseases, including rheumatoid arthritis, are characterized by increased insulin resistance, a phenomenon that is thought to be a contributor to adverse cardiovascular outcomes in rheumatoid arthritis through nontraditional mechanisms,” the authors wrote.

The findings are based on an assessment of disease activity in rheumatoid arthritis patients. They were assessed for cardiovascular risk factors, including insulin resistance and body mass index.

The study included 92 patients of which 66% were female and 72% were positive for rheumatoid factor. At baseline, the mean values for swollen joint count in 28 joints (SJC28), tender joint count in 28 joints (TJC28), and Disease Activity Score in 28 joints (DAS28) were 3.7 ± 4.4, 3.6 ± 5.2, and 3.5 ± 1.5, respectively. The mean BMI was 28 ± 7 kg/m with 70% of patients having a BMI higher than >25 kg/m. Insulin resistence was present in 26% of patients and 5% of patients had diabetes. They patients were being treated with DMARDs (80%), biologics (29%), and steroids (19%).

The patients, including a second group with osteoarthritis, underwent synovial tissue testing for glucose transporter 1 (GLUT ‐1) and GLUT‐4 activity. GLUT-1 expression was greater in the synovium of rheumatoid arthritis (RA) patients (n = 26) as compared to patients with osteoarthritis (n = 16). RA patients showed increased expression in the lining, sublining, and vascular regions. But, decreased GLUT‐4 expression was found in the RA lining layer in 21 patients as compared to only eight osteoarthritis patients.

When GLUT-1 protein expression decreased, p‐AMPK protein expression in synovial fluid increased in in four patients who were treated with metformin, which increased glycolytic activity and decreased oxidative phosphorylation in rheumatoid arthritis synovial fibroblasts in seven patients. RA patients who were taking metformin or aminoimidazole carboxamide ribonucleotide, demonstrated a reduced spontaneous production of interleukin‐6 (IL ‐6), IL ‐8, and monocyte chemotactic protein 1 in synovial explants and fibroblasts.

“The results of the present study highlight a relationship between insulin resistance and disease activity in rheumatoid arthritis. Furthermore, we demonstrated down‐regulation of inflammatory responses in ex vivo rheumatoid arthritis synovial explant cultures and rheumatoid arthritis synovial fibroblasts cell cultures by metformin, as well as evidence to suggest that alteration in glucose pathways may ameliorate disease activity in rheumatoid arthritis,” they wrote.

REFERNCE: Lorna Gallagher  Sian Cregan  Monika Biniecka  Clare Cunningham  Douglas J. Veale  David J. Kane  Ursula Fearon  Ronan H. Mullan. "Insulin‐Resistant Pathways Are Associated With Disease Activity in Rheumatoid Arthritis and Are Subject to Disease Modification Through Metabolic Reprogramming: A Potential Novel Therapeutic Approach," Arthritis and Rheumatology. Frst published:16 December 2019 https://doi.org/10.1002/art.41190