Complement C3 Predicts Whole-Body Insulin Resistance in PsA

Insulin resistance in inflammatory disorders is thought to be partly mediated by the effects of tumor necrosis factor (TNF)-α and other cytokines on glucose homeostasis. The observation that insulin sensitivity improves with disease-modifying antirheumatic drug (DMARD) initiation in PsA further supports this hypothesis. However, testing for insulin resistance using the glucose clamp technique or surrogate indices is complex and time-consuming to perform in the clinical setting.

Francesco Ursini, MD, of the University of Catanzaro in Italy, and colleagues found in a prior study that serum complement C3 served as an accurate predictor of insulin resistance in previously untreated patients with PsA, but the results were limited to hepatic insulin resistance only. It is now recognized that adipose tissue and skeletal muscle play important roles mediating insulin resistance. The current study evaluated the relationship between serum C3 levels and whole-body insulin sensitivity in nondiabetic patients with PsA.

A total of 40 patients underwent an oral glucose tolerance test, and the results were used to determine insulin resistance, early phase insulin secretion, and β-cell function, as measured by the insulin sensitivity index (ISI), insulinogenic index (IGI), and oral disposition index (ODI), respectively. Insulin resistance was defined as ISI ≤2.5.

Decreased insulin sensitivity (ISI) and β-cell function (ODI) were associated with increased diastolic blood pressure (P = .004 and P = .03), systolic blood pressure (P = .001 and P = .02), and complement C3 levels (P = .006 and P = .02) in univariate analysis.

No correlations were found between ISI or ODI and erythrocyte sedimentation rate, C-reactive protein, or body mass index. Early phase insulin secretion (IGI) was not associated with any variables evaluated in this study. After stepwise multiple regression, approximately 50% of the variance of ISI was attributed to complement C3.

After receiver operating characteristic (ROC) curve generation, the authors determined that the ideal threshold for identifying patience with insulin-resistance  using serum C3 levels was 1.32 g/L, which has a sensitivity of 56% and a specificity of 96%.

Summary and Clinical Applicability

Insulin resistance is common in PsA and other inflammatory disorders, but assessing for insulin resistance in daily clinical practice is complex and difficult. Using measures of insulin resistance derived from oral glucose tolerance tests, the authors found a significant association between serum complement C3 levels and whole-body insulin resistance in PsA.

“Our data suggest that serum C3 >1.32 g/L could represent a useful marker of insulin sensitivity in [patients with PsA], easy to use in clinical practice. Larger studies are needed to evaluate the role of C3 in predicting future development of diabetes in PsA and to accurately establish optimal C3 cut-off for the identification of insulin-resistant in [patients with PsA],” the study authors concluded.

Limitations and Disclosures

• Only a small number of patients were enrolled, which prevented analyses of potential confounding factors

• The correlation between visceral adipose tissue and serum C3 levels could not be demonstrated since only body mass index, but not waist circumference, was measured

References

Ursini F, D’Angelo S, Russo E, et al. Complement C3 Is the strongest predictor of whole-body insulin sensitivity in psoriatic arthritis. PLoS One. 2016;11(9):e0163464. doi: 10.1371/journal.pone.0163464.

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