Effects of systemic TNF inhibition on postprandial glucose-regulatory hormones in inflammatory arthritis

The effects of systemic tumour necrosis factor (TNF) inhibition on glucose homeostasis are not fully understood. This study aims to evaluate the effects of TNF inhibitors (TNFis) on gastric inhibitory polypeptide (GIP), amylin and pancreatic polypeptide (PP), hormones involved in the fine-tuning of postprandial glucose homeostasis, in patients with RA, PsA and axial spondylarthritis (axSpA).

Sixty-four non-diabetic patients (RA, n = 22; PsA, n = 13; axSpA, n = 29) undergoing TNFi therapy were prospectively evaluated at baseline and after 12, 24 and 52 weeks. Assessments included measurements of disease activity, acute-phase reactants, fasting glucose, insulin and C-peptide levels, insulin resistance as assessed by the updated Homeostatic Model Assessment (HOMA)2 and lipid profile. Serum concentrations of amylin, GIP and PP were measured at each visit. Multivariable linear mixed-effects models were used to analyse temporal changes in clinical and biochemical variables.

Basal insulin resistance indices did not significantly change throughout the study in patients with RA, PsA or axSpA. However, serum basal levels of GIP, amylin and PP significantly increased in the univariable model, and the results remained consistent after adjusting for CRP, at 12, 24 and 52 weeks of TNFi therapy. These effects were consistent and specific across different TNFi types and diagnoses, except for PP, which exhibited a significant interaction with the type of arthritis.

In patients initiating TNFi therapy, serum levels of GIP, amylin and PP increase regardless of systemic inflammation. This effect on postprandial glucose-regulating hormones may help explain the cardiovascular benefits of TNFi in rheumatic inflammatory diseases, at least in part.