Background/Purpose: In non-diabetic healthy individuals insulin secretion and insulin sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA).

Methods: Cross-sectional study encompassing 361 non-diabetic individuals, 151 RA and 210 controls. Insulin, C-peptide and IR indexes by homeostatic model assessment (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indexes between patients and controls. Non-linear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion.

Results: HOMA2-S% was lower in RA patients than in controls after adjusting for traditional IR-related factors and prednisone intake (105 ± 53 vs. 108 ± 75, p=0.006). Insulin (9.8 ± 6.5 vs. 13.0 ± 13.4 U/ml, p=0.007) and C-peptide serum levels (1.53 ± 0.77 vs. 3.37 ± 2.94 ng/ml, p=0.000) were found to be up-regulated in RA patients. The insulin to C-peptide ratio was lower in RA patients (0.14 ± 0.07 vs. 0.08 ± 0.02, p=0.000) after multivariate adjustment including glucocorticoids. Traditional IR-related factors strongly correlated with glucose, insulin, C-peptide, and IR indexes in both patients and controls. However, Pearson’s correlation coefficients were lower in patients. This shows that the variability in glucose homeostasis molecules or IR indexes had a weaker association with traditional IR-related factors in RA patients. Linear relations between glucose homeostasis molecules (glucose, insulin and C-peptide) and HOMA2 indexes showed high values that reached statistical significance. However, the relation of C-peptide with insulin, HOMA2-IR with C-peptide, and the relation of HOMA2-%B with insulin and C-peptide were lower in patients with RA than in controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients after multivariable analysis (0.08±0.02 vs. 0.14±0.07, p=0.000). The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients: the variability explained by the curve (non-linear r²=0.690 vs. r²=0.899, p=0.000) and beta coefficients (-0.87[95%CI -0.95–0.78] vs. -0.98[95%CI -1.04–0.92] ng/ml, p=0.034) were lower in RA.

Conclusion: The traditional factors associated with IR in healthy individuals are less related to IR in RA patients. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationship-between-insulin-sensitivity-and-beta-cell-secretion-in-non-diabetic-rheumatoid-arthritis-subjects/