| Background:Schizophrenia(SCZ)is a kind of severe mental disorder. It is conducted in a lot epidemiological study that the prevalence of Diabetes mellitus (DM) in schizophrenia is higher than normal people. However, atypical antipsychotics are widely used in clinical as first-class drugs and their effects in the glucose metabolism is a confuse factor when studying the relationship of SCZ and DM. It is reported in a small number studies that glucose metabolic disorder is more severe in first-episode drug-na?ve schizophrenia patients than in controls. But there are still some contradictions.Low level inflammatory condition is found to be a possible pathophysiologic process to schizophrenia as inflammation factors concentrations are higher in plasma and cerebrospinal fluid of patients than in controls. The relationship of interleukin-1 (IL-1) and schizophrenia drive much attention of researchers in recent years. IL-1 is a central inflammatory factor in vivo and IL-1βis the major active subtype. Interleukin-1 receptor antagonistα(IL-1Rα)is the natural antagonist of IL-1βand regulate its concentration. At the same time, it is conducted in a lot researches that glucose metabolism of diabetes patients is related to the disorder of IL-1βand IL-1Rα. Recombinant IL-1Rαis proved to be effective to improve glycemia andβ-cell secretory function and reduce markers of systemic inflammation . Up to date, there still no literature reports if there is any relationship between glucose metabolism and IL-1βlevel in first-episode drug naive schizophrenia.We suppose that there is condition independently glucose metabolic disorder in schizophrenia and it is related to the high level of IL-1β. The patients enrolled in most study with regard to schizophrenia and diabetes are not drug-naive condition, so it is difficult to detect the glucose metabolic status without confounding factors. Therefore, we decide to enroll frist-episode drug-naive patients to detect the glucose metabolism and its relationship with IL-1βand IL-1Rα.Objective:1. To compare the glucose metabolic index level of first-episode drug-naive schizophrenia and healthy controls; To find out the trait marker of glucose metabolism in schizophrenia and its relationship with clinical characteristics2. To compare the serum IL-1βand IL-1Rαlevel in first-episode drug-naive schizophrenia and healthy controls and its relationship with clinical characteristics.3. To investigate the pathway of inflammatory markers IL-1βand IL-1Rαto the glucose metabolic disorder in first-episode drug-naive schizophrenia.Methods:1. First-episode in-patients from Guangzhou Brain Hospital(affiliated hospital of Guangzhou Medical College)were screened. Patients who met the schizophrenia diagnosis criteria of Domestic criteria of mental disorde(rCCMD-3)were enrolled. Healthy controls were staff and interns of this hospital.2. Demographic and clinical questionare, Postive and negative syndrome scale(PANSS), Personal and social scale(PSP), Young mania rating scale(YMRS), Hamilton depression scale-17(HAMD-17), and Nottingham onset schedule (NOS) were evaluated.3. Fasting plasma glucose(FPG), Post-prandial blood glucose(PBG), Fasting plasma insulin(FPI), Total cholesterol(TC), Total triglyceride(TG), High density lipid-cholesterol(HDL-C), and Low density lipid-cholesterol(LDL-C ) of all samples were evaluated. Insulin resistance index was calculated by HOMA2-IR software through the evaluation of FPG and FPI. Serum concentrations of IL-1βand IL-1Rαwere detected by ELISA in all samples. 4. SPSS 13.0 soft was used to statistic analyzed. We used the explore function of the soft to analyse the data first. The indices of glucose metabolism and IL-1βand IL-1Rαof patients and controls were compared. T-test was used to analyzed with normal distribution data and non-parametric test was used to analyzed abnormal distribution data. Relations of clinical characteristics and glucose metabolism and IL-1βand IL-1Rαwere analyzed with Spearman or Pearson correlation analysis according to the distribution of the data. Influence factors of glucose metabolism were statistical analyzed with Logistic regression analysis.Results:1. Fourty-seven patients met the schizophrenia criteria of CCMD-3 were enrolled. The mean abdominal circumference of patients was smalle(rZ=-2.540,P=0.011). The levels of PBG (6.48±1.49vs4.97±0.88,t=-5.134,P<0.001), LDL-C(Z=-3.056,P=0.002) , and HDL-C (1.52±0.32vs1.69±0.26,t=2.373,P=0.020 ) were lower in patients. The ratio of impaired fasting glucose(IFG)(14.9%vs0%,P=0.038) in schizophrenia group was significantly higher, and so as that of impaired glucose tolerance(IGT)(23.4%vs0%,P=0.002). There was no difference with BMI,FPI,HOMA2-IR,FPG,TC,TG in patients and control. The serum level of FPG in patients was related to duration of untreated psychosis(Spearman,r=0.306,P<0.05)and duration of untreated illness(Spearman,r=0.306,P<0.05). The negative score of PANSS was related to the levels of FPG(Pearson,r=0.427,P<0.01)and PBG(Pearson,r=0.427,P<0.01).2. The serum level of IL-1βin first-episode drug-na?ve schizophrenia was significantly highter than controls(22.35±6.33vs5.40±4.42 ,t=-13.107,P<0.001)and the level of IL-1Rαwas lower but didn't meet the significance(172.05±58.07vs203.48±80.93,t=1.897,P=0.063). The concentration of IL-1βin patients was to mildly related to negative score(Pearson,r=0.366,P<0.05) and total score of PANSS(Pearson,r=0.378,P<0.01). The concentration of IL-1Rαwas related to negative score of PANSS(Pearson,r=-0.385,P<0.01). The PBG in patients were moderately related to IL-1β(Pearson,r=0.414, P<0.05)and IL-1Rα(Pearson ,r=-0.513,P<0.05).3. Tha patients were divided into IGR(Impaired glucose regulation, including IFG and IGT)group and non-IGR group, and IL-1βand IL-1Rαlevel of two groups were compared with that of healthy controls.The IL-1βlevel the three groups were 26.25±5.25ng/ml,21.00±6.17 ng/m and 5.40±4.43 ng/ml , the total difference was significant(F=98.489, P<0.001). It was significant in pairwise comparison also(P<0.01). The IL-1Rαlevel in the three groups were 123.15±38.46ng/ml,188.81±54.32ng/ml and 203.58±80.93ng/ml in increase sequence of the three group and it total difference was significant(F=13.517,P<0.001). The IL-1Rαlevel of IGR group was lower than that of non-IGR(P<0.001),but there was no difference between the latter and controls(P>0.05).4. Being IGR or not of patients was defined to be dependent factor and DUP,DUI,PANSS total score,negative score of PANSS, aggressive score of PSP,IL-1βand IL-1Rαlevel were defined to be independent factors. It was suggested in the Logistic regression that IL-1β(OR:1.616,95%CI:1.100~2.373,P<0.05)was risk factors of developing IGR.Conclusions:1. Schizophrenia patients have glucose metabolic disorder compare to healthy controls. PBG is an important biomarker of glucose disturbance in schizophrenia patients and it is related to negative syndrome.2. There is inflammation disturbance in schizophrenia patients. The serum level of IL-1βand IL-1Rαare related to negative syndrome.3. The glucose metabolic disturbance of SCZ is related to serum level of inflammation factor IL-1β. |
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