The serum lipopolysaccharide level in people with different glucose tolerances and its relationship with insulin resistance and β-cell secretory function

Abstract

Objective To investigate serum lipopolysaccharide (LPS) level in people with different glucose tolerances and to explore the relationship between LPS and insulin resistance/β-cell secretory function.Methods Sixty-seven subjects were recruited,including 23 with newly diagnosed type 2 diabetes ( T2DM),21 impaired glucose tolerance ( IGT),and 23 normal glucose tolerance (NGT).Serum LPS was assayed by limulus amebocyte lysate test ;expression of LPS toll-like receptor 4 (TLR4) on surface of plasma monocytes was measured by flow cytometric assays,and the changes of LPS levels by 0.5 hours and 2 hours after a high-fat diet were detected.Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR); β-cell secretory function was evaluated by homeostasis model assessment for β3 cell function ( HOMA-β )/HOMA-IR,increment in insulin in the first 30 minutes/increment in glucose in the first 30 minutes ( AIns30/ΔG30)/HOMA-IR,AUCIns120min/HOMA-IR.Results 2 h LPS levels after a high-fat diet were significantly higher than fasting LPS levels [ NGT:0.96(0.33,0.99)vs 0.62 (0.22,0.64),IGT:1.08(0.53,1.22)vs 0.71 (0.39,0.82),T2DM:1.23 (0.62,1.43)vs 0.86( 0.45,0.94 ),EU/ml,all P＜0.01 ].Fasting,0.5 h,and 2 h LPS levels and fasting TLR4 levels of T2 DM group and IGT group were respectively higher than those of NGT group [ fasting LPS:0.86( 0.45,0.94 ),0.71 ( 0.39,0.82 ) vs 0.62(0.22,0.64),EU/ml;0.5 h LPS:1.10(0.55,1.18),0.84(0.50,1.07) vs 0.73(0.31,0.76),EU/ml;2 h LPS:1.23(0.62,1.43),1.08(0.53,1.22)vs 0.96(0.33,0.99),EU/ml; fasting TLR4:36.96( 17.22,55.19),30.34 ( 15.00,45.18 )vs 15.66 (6.09,9.76),MIF/105 cells,all P＜0.01 ].Fasting LPS,AUCLPS 120 min,and fasting TLR4 were positively correlated with insulin resistance index and negatively correlated with β-cell secretory function index ( P＜0.05 ).Multiple linear regression analysis showed that fasting LPS was an independent correlative factor of HOMA-IR and 0.5 h LPS was an independent correlative factor of (AIns30/AG30)/HOMA-IR and AUCIns Ins120min/HOMA-IR.Conclusion People with different glucose tolerances show differed LPS levels and its receptor TLR4 levcls,both of which are correlated with insulin resistance and β-cell secretory function,suggesting that LPS is associated with the pathogenesis of abnormal glucose regulation. Key words: Lipopolysaccharide ; Toll-like receptor 4 ; Insulin resistance ; β-cell secretory function