Implications of increased circulating macrophage inhibitory protein-5 in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) which is regarded as an inflammatory disease is associated with several chemokines, although the association with macrophage inhibitory protein-5 (MIP-5) which has a chemotaxis for many immune cells has not been reported. This study was designed to determine the circulating level of MIP-5 as well as clinical significance in T2DM patients.

MIP-5 was measured in sera of 156 T2DM patients and 20 healthy controls (HCs). The association of serum MIP-5 with various clinical and laboratory characteristics of T2DM was analyzed.

Serum MIP-5 levels were significantly elevated in T2DM patients compared with HCs (P < 0.001). The univariate analyses revealed that increased serum MIP-5 was associated with age, disease duration, fasting serum insulin and C-peptide, serum urea, creatinine, urinary albumin-to-creatinine ratio (uACR), estimated glomerular filtration rate (eGFR), hypertension, coronary artery disease (CAD), peripheral neuropathy (PN), peripheral artery disease (PAD), diabetic ketosis (DK), diabetic kidney disease (DKD) and Repaglinide medication (all P < 0.05). The multivariate linear regression analysis showed that CAD (P = 0.046), eGFR (P < 0.001) and uACR (P = 0.004) remained significantly associated with serum MIP-5, but other variables did not. The multivariate logistic regression analysis showed that increased MIP-5 was independently associated with increased risk of DKD development (OR, 95 %CI, 1.044, 1.003-1.086, P = 0.034), but not with CAD in T2DM patients (OR, 95 %CI, 1.029, 0.990-1.069, P = 0.144). The correlations among MIP-5, eGFR and uACR were compared between patients with and without DKD. Serum MIP-5 correlated negatively with eGFR, but did not with uACR, in T2DM patient both with and without DKD. uACR correlated negatively with eGFR in T2DM patients without DKD, but did not in those with DKD.

The present study indicates that circulating MIP-5 is increased in T2DM patients and associated closely with DKD risk and renal decline. Therefore, circulating MIP-5 may be a novel and potential biomarker for T2DM and DKD.