Rheumatoid Arthritis Inflammation Linked With Insulin Resistance

The incretin-insulin axis is impaired in patients who have rheumatoid arthritis, both during fasting and postprandial.

Beatriz Tejera-Segura and colleagues at the Hospital Universitario de Canarias, Tenerife, Spain, and other centers suggested that the precise mechanism that links systemic inflammation with insulin resistance in patients with rheumatoid arthritis remains elusive.

So they conducted a cross-sectional study to determine whether the incretin-insulin axis and incretin effect are disrupted in patients with rheumatoid arthritis and whether they are related to the insulin resistance found in these patients.

The authors reported their findings in Arthritis Research & Therapy.

Their study included 361 subjects who did not have diabetes. Of them, 151 had rheumatoid arthritis and 210 were sex-matched controls. Because patients and controls with diabetes were not included in the study, none of the patients or controls were receiving glucose-lowering drugs or insulin therapy.

The investigators assessed insulin, C-peptide, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 (DPP-4) soluble form, and insulin resistance indexes by homeostatic model assessment (HOMA2, the updated computer HOMA model), and performed a multivariable analysis adjusted for insulin resistance–related factors.

They further studied the postprandial differences of these molecules between patients and controls by having 10 patients and 10 controls undergo a 566-kcal meal test.

Following are some of the results:

• Insulin, C-peptide, and HOMA2-IR indexes were higher in patients than in controls.

• This was also the case for GLP-1.

• The differences remained significant after multivariable adjustment, including glucocorticoid intake.

• Disease Activity Score in 28 joints with erythrocyte sedimentation rate and Clinical Disease Activity Index were associated with DPP-4 serum levels.

• GLP-1 positively correlated with β-cell function (HOMA2 of β-cell production calculated with C-peptide) in patients but not in controls.

• The meal test in patients who had rheumatoid arthritis revealed a higher total and late response AUC for glucose response, a later maximal response of C-peptide, and a flatter curve in GIP response.

The researchers suggested that their study, probably the first assessment of the incretin-insulin axis and the incretin effect in rheumatoid arthritis, shows that metabolic hormones are impaired in patients who have rheumatoid arthritis.

“The presence of this impairment reinforces the concept that the disease itself, probably by means of the effect of inflammation, leads to an IR state,” they concluded. “Our results demonstrate the existence of a mechanism linking inflammation with IR that warrants further studies.”

References:

Tejera-Segura B, López-Mejías R, Domínguez-Luis MJ, et al. “Incretins in patients with rheumatoid arthritis.” Arthritis Res Ther. 2017 Oct 17;19(1):229. doi: 10.1186/s13075-017-1431-1439.