Serum fatty acid-binding protein 4 levels and responses of pancreatic islet β-cells and α-cells in patients with type 2 diabetes

Abstract

Background: Serum fatty acid-binding protein 4 (FABP4), as an intracellular lipid chaperone and adipokine, was reported to be related to the incidence of type 2 diabetes (T2D) and diabetic complications, but its association with pancreatic islet β-cell and α-cell functions has not been fully elucidated. So the present study was to investigate the serum FABP4 levels and responses of islet β-cells and α-cells in patients with T2D.

Methods: 115 patients with T2D and 89 healthy controls (HC), who received serum FABP4 levels test, were recruited to participate in this study. Moreover, 75-g oral glucose tolerance test (OGTT) was performed in T2D patients to evaluate islet β-cell and α-cell functions. Systemic insulin sensitivity and overall insulin secretion of islet β-cell function were assessed by Matsuda index using C peptide (ISI_M-cp) and ratio of the area under the C peptide curve to the glucose curve (AUC_cp/glu) during OGTT, respectively. Fasting glucagon (Gluca_0min) and postchallenge glucagon assessed by the area under the glucagon curve (AUC_gluca) were determined during OGTT to evaluate islet α-cell function. And other various clinical variables were also measured in all participants. Skewed variables were natural log-transformed (ln), such as lnFABP4.

Results: The serum FABP4 levels in T2D patients were significantly higher than those in HC (p < 0.05). And after partially adjusting for fasting plasma glucose, serum lnFABP4 levels were negatively correlated with lnISI_M-cp (r = - 0.332, p < 0.001) and positively correlated with lnAUC_cp/glu (r = 0.324, p < 0.001), lnGluca_0min (r = 0.200, p = 0.040) and lnAUC_gluca (r = 0.311, p < 0.001), respectively, in patients with T2D. Furthermore, when multiple linear regression analyses were applied to adjust for other various clinical variables, serum lnFABP4 levels were found to remain associated with lnISI_M-cp (β = - 0.296, t = - 2.900, p = 0.005), lnAUC_cp/glu (β = 0.223, t = 2.038, p = 0.046), lnGluca_0min (β = 0.272, t = 2.330, p = 0.024) and lnAUC_gluca (β = 0.341, t = 3.065, p = 0.004), respectively.

Conclusion: Increased serum FABP4 levels were closely associated with blunted insulin sensitivity, increased insulin secretion, and elevated fasting and postchallenge glucagon levels in patients with T2D.

Keywords: FABP4; Type 2 diabetes; α-cell function; β-cell function.

Fig. 1

Levels of serum FABP4 in HC and patients with T2D

Fig. 2

Relationships between serum FABP4 and islet β-cell and α-cell function indices in patients with T2D by univariate analysis (a ISI_M-cp; b AUC_cp/glu; c Gluca_0min; d AUC_gluca)

Fig. 3

Relationships between serum FABP4 and islet β-cell and α-cell function indices in patients with T2D after adjusting for FPG (a ISI_M-cp; b AUC_cp/glu; c Gluca_0min; d AUC_gluca)