Serum complement C3 and islet β-cell function in patients with type 2 diabetes: A 4.6-year prospective follow-up study

Purpose Serum complement C3 has been shown to contribute to the incidence of type 2 diabetes (T2D), but how serum complement C3 affects islet β-cell function throughout the course of T2D is unclear. This study explored whether serum complement C3 is independently associated with changes in islet β-cell function over time in patients with T2D. Methods Serum complement C3 was measured, and endogenous β-cell function was evaluated by area under the C-peptide curve (AUC cp ) during an oral glucose tolerance test (OGTT) in 411 patients with T2D at baseline from 2011 to 2015. Next, 347 of those patients with available data were pooled for a final follow-up analysis from 2014 to 2018. Changes in islet β-cell function at follow-up were evaluated by AUC cp percentage changes (ΔAUC cp %). In addition, other possible clinical risks for diabetes were also examined. Results The 347 patients included in the analysis had a diabetes duration of 4.84 ± 3.63 years at baseline. Baseline serum complement C3 (baseline C3) levels were positively correlated with baseline natural logarithm of AUC cp (lnAUC cp ) ( n = 347, r = 0.288, p < 0.001), and baseline C3 was independently associated with baseline lnAUC cp ( β = 0.17, t = 3.52, p < 0.001) after adjustment for baseline glycemic status and other clinical confounders by multivariate liner regression analysis. Compared with the baseline values, complement C3 changes (ΔC3) and ΔAUC cp % was –0.15 ± 0.28 mg/ml and –17.2 ± 18.4%, respectively, at a follow-up visit 4.57 ± 0.78 years later. Moreover, ΔC3 was positively correlated with ΔAUC cp % ( n = 347, r = 0.302, p < 0.001). Furthermore, each 0.1 mg/ml increase in ΔC3 was associated with a higher ΔAUC cp % (1.41% [95% CI, 0.82–2.00%]) after adjusting for changes in glycemic status and other clinical confounders at follow-up. Conclusions In addition to serum complement C3 being independently associated with islet β-cell function at baseline, its changes were also independently associated with changes in islet β-cell function over time in patients with T2D.