Complement C3 Is the Strongest Predictor of Whole-Body Insulin Sensitivity in Psoriatic Arthritis

Abstract

ObjectivesTo evaluate the correlation between inflammatory measures and whole-body insulin sensitivity in psoriatic arthritis (PsA) patients.MethodsFor the present study, 40 nondiabetic PsA patients were recruited. A standard oral glucose tolerance test (OGTT) was performed. The insulin sensitivity index (ISI), insulinogenic index (IGI) and oral disposition index (ODI) were calculated from dynamic values of glucose and insulin obtained during OGTT.ResultsIn our study population, mean ISI was 3.5 ± 2.5, median IGI was 1.2 (0.7–1.8), mean ODI 4.5 ± 4.5. In univariate correlation analysis, ISI correlated inversely with systolic blood pressure (sBP) (R = -0.52, p = 0.001), diastolic blood pressure (dBP) (R = -0.45, p = 0.004) and complement C3 (R = -0.43, p = 0.006) and ODI correlated inversely with sBP (R = -0.38, p = 0.02), dBP (R = -0.35, p = 0.03) and complement C3 (R = -0.37, p = 0.02). No significant correlations were found between analyzed variables and IGI. In a stepwise multiple regression, only complement C3 entered in the regression equation and accounted for approximately 50% of the variance of ISI. Using a receiver operating characteristic (ROC) curve we identified the best cut-off for complement C3 of 1.32 g/L that yielded a sensitivity of 56% and a specificity of 96% for classification of insulin resistant patients.ConclusionsIn conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients.

Complement C3 and fatty liver disease in Rheumatoid arthritis patients: a cross-sectional study

“…Moreover, two large clinical studies confirmed the association between C3 levels and NAFLD [24,25] independently of other metabolic features. Further, these data integrate our previous studies in which complement C3 was identified as the strongest predictor of insulin resistance in RA and PsA patients [26][27][28], despite in this study, we have not found any significant correlation between the presence of NAFLD and increased insulin resistance, thus supporting the hypothesis that complement C3 may reflect different mechanisms of metabolic derangement. In our cohort we found an overall prevalence of NAFLD in RA of 25%.…”

“…Complement system activation [22] has been shown in liver biopsies from patients with NAFLD compared to healthy controls [23]. Moreover, our group previously demonstrated a significant association between complement C3 and insulin resistance (IR) in psoriatic arthritis (PsA) [26,27] and RA patients [28][29][30]. Moreover, our group previously demonstrated a significant association between complement C3 and insulin resistance (IR) in psoriatic arthritis (PsA) [26,27] and RA patients [28][29][30].…”

“…More recently, circulating C3 levels have been demonstrated to predict the presence of NAFLD in large cohorts from general population independently of the most plausible confounders such as MS and obesity [24,25]. Moreover, our group previously demonstrated a significant association between complement C3 and insulin resistance (IR) in psoriatic arthritis (PsA) [26,27] and RA patients [28][29][30].…”

Response to the letter to the editor by Shadmani et al

“…However, we feel the need to clarify that the main aim of our manuscript was not that of confirming a direct, unimpeachable, unidirectional causal correlation between complement C3 and the future development of NAFLD, but rather to provide a hypothesis-generating basis for further, adequately powered longitudinal studies aiming at investigating in details the processes linking complement system to metabolic disturbances in RA patients, as already suggested by other studies published by our group. [2][3][4] ORCID Francesco Ursini…”

“…We truly appreciated the precious and highly qualified contribution-given the leading expertise of the authors in the field of biostatistics and epidemiology-and largely agree with them that the crosssectional design of our study may significantly limit the ability of our results to support definitive conclusions regarding the direction of the relationship between C3 and NAFLD.However, we feel the need to clarify that the main aim of our manuscript was not that of confirming a direct, unimpeachable, unidirectional causal correlation between complement C3 and the future development of NAFLD, but rather to provide a hypothesis-generating basis for further, adequately powered longitudinal studies aiming at investigating in details the processes linking complement system to metabolic disturbances in RA patients, as already suggested by other studies published by our group. [2][3][4] ORCID Francesco Ursini…”