Adipocyte Fatty Acid Binding Protein And Subclinical Atherosclerosis In Type 2 Diabetes Mullitus

Objective:To explore the predictive effect of metabolic syndrome (MS) score on subclinical atherosclerosis (subAS) in patients with newly-diagnosed type 2 diabetes (T2DM) under multifactorial intervention.Methods:In the prospective study,141 patients with newly-diagnosed T2DM without subAS were designed to experience the multifactorial intervention, including intensive control of blood glucose, blood pressure, blood lipids and body weight. The predictive effect of MS score on the incidence of subAS after 6 years was analyzed.Results:MS scores after 1 year intervention were significantly improved (P<0.01). The subAS incidence rate after 6 years of patients whose MS scores remained equal to or greater than 2 after 1 year intervention was significantly higher than that of those whose MS scores were 0 or 1 after 1 year intervention (P<0.05). The subAS incidence rate of those whose MS scores remained 2 after 1 year intervention was 74.1%(20/27), while the subAS incidence rate of those whose MS scores remained 3 after 1 year intervention was 100.0%(6/6). Multiple stepwise Logistic regression analysis showed that after adjustment of age and sex, MS score after 1 year intervention was the independent variable of subAS after 6 years (OR,1.89; 95% CI,1.19 to 3.01, P<0.01). Further analysis revealed that after adjustment of age and sex, central obesity after 1 year intervention was the most marked factor on subAS after 6 years among all the MS components except for hyperglycemia (OR,2.45; 95%CI,1.19 to 5.07, P<0.05).Conclusion:The early-stage MS score may predict long-term subAS outcome in patients with newly-diagnosed T2DM under multifactorial intervention. Obesity is the most important factor which deteriorates long-term subAS. Objective:Adipocyte fatty acid binding protein (A-FABP), a 15-kD protein mainly derived from adipocytes and mocrophages, plays a central role in the development of type 2 diabetes (T2DM), metabolic syndrome (MS) and atherosclerosis. In the present study, we evaluated the association of A-FABP with MS and prediction on subclinical atherosclerosis (subAS) in patients with T2DM under multifactorial intervention.Methods:In the present study,133 patients with newly-diagnosed T2DM were prospectively followed up for 6 years under multifactorial intervention. A-FABP was detected by double antibody sandwich ELISA in fasting status in plasma of baseline, year 1 to 6. The association of plasma A-FABP with MS in respective year and the predictive effect of plasma A-FABP on subAS after 6 years were investigated.Results:①At baseline, after adjusted for age and sex, plasma A-FABP was positively associated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), total cholesterol (TC) and homeostasis model assessment of insulin resistance index (HOMA-IR) (P＜0.05). At year 3 and year 6, after adjusted for age, sex and pharmacological treatments, plasma A-FABP was positively associated with BMI, WC, WHR and HOMA-IR (P＜0.05). Plasma A-FABP levels were divided into sex-specific higher level and lower level by dichotomy. At baseline, after adjusted for age, WC, HbA1c, low density lipoprotein cholesterol (LDL-C), HOMA-IR, high sensitivity C-reactive protein (hsCRP) and adiponectin, sex-specific higher plasma A-FABP level was associated with MS (OR,2.46; 95% CI,1.05 to 5.78; higher vs lower sex-specific dichotomy, P<0.05). At year 3 and year 6, after adjusted for indexes above and pharmacological treatments, sex-specific higher plasma A-FABP level was associated with MS (OR, 2.62 and 2.60; 95% CI,1.14 to 6.01 and 1.09 to 6.20; higher vs lower sex-specific dichotomy, P both<0.05).②Multiple stepwise Logistic regression analysis showed that, after adjustment of age, sex, and pharmacological treatments, plasma A-FABP at year 1 was the independent variable of subAS after 6 years (OR,3.08; 95% CI,1.22 to 7.75, P＜0.05), rather than plasma A-FABP at baseline or year 2 to 6.Conclusion:Plasma A-FABP is associated with obesity and MS in type 2 diabetics under multifactorial intervention. Plasma A-FABP after early-stage multifactorial intervention may predict long-term subAS outcome in patients with newly-diagnosed T2DM. Objective:To explore the impact on adipocyte fatty acid binding protein (A-FABP) expression in THP-1 macrophages by serum of patients with type 2 diabetes (T2DM), metabolic syndrome (MS) or subclinical atherosclerosis (subAS).Methods:THP-1 macrophages, which were derived from THP-1 monocytes and cultured in serum, were derived into 5 groups: T2DM+MS-subAS- group (n=10), T2DM+MS+subAS- group (n=10), T2DM+MS-subAS+ group (n=10), T2DM+MS+subAS+ group (n=10) and normal control group (n=10). Each group was conducted with 3 treatments:serum intervention, serum+LPS intervention and serum+LPS+A-FABP inhibitor intervention. TLR4 and phospho-JNK expression were detected by Western blot; TLR4 and A-FABP mRNA expression were measured by RT-PCR; A-FABP levels in serum, cell lysate and culture medium were tested by ELISA.Results:After cultured in serum for 24h, TLR4, phospho-JNK and A-FABP expression in THP-1 macrophages as well as A-FABP level in culture medium were significantly higher in T2DM groups than which in normal control group, similarly in T2DM with MS groups than which in T2DM without MS groups, as well as in T2DM+MS+subAS+ group than which in T2DM+MS+subAS- group. After LPS treatment, TLR4, phospho-JNK and A-FABP expression in THP-1 macrophages as well as A-FABP level in culture medium, which were all increased in 5 groups significantly, were higher in T2DM groups than normal control group, and in T2DM with MS groups than which in T2DM without MS groups, and in T2DM+MS+subAS+ group than which in T2DM+MS+subAS-group. However, LPS treatment after A-FABP selective inhibitor incubation caused significantly decreasement of TLR4, phospho-JNK and A-FABP expression in THP-1 macrophages as well as A-FABP level in culture medium in all 5 groups than LPS treatment alone, and there were no significant differences between T2DM+MS-subAS- group, T2DM+MS-subAS+ group and normal control group.Conclusion:Serum from T2DM can activate TLR4/JNK signaling and A-FABP expression in THP-1 macrophages, which has higher activation extent with serum of T2DM with MS or with subAS. A-FABP selective inhibitor may downregulate activation of TLR4/JNK signaling and A-FABP expression induced by LPS based on serum of T2DM, MS or subAS patients.