Relationship Between Plasma Leptin, C-Peptide And Weight Gain, Glucose Regulation Induced By Clozapine

Background : A lot of researches have indicated thatantipsychotics have relationship with the weight gain of schizophrenia patients, especially atypical antipsychotics. Most researches have been performed on clozapine .At the same time clozapine can induce glycometabolism abnormality and even can induce diabetes mellitus, while risperidone has little effect on glycometabolism. It is well known that clozapine has a certain effect on schizophrenic patients, added its poor price, clozapine is used widely in Chinese primary hospital today.Objective: To observe the effects of clozapine on plasma leptin,C-peptide, plasma glucose and weight, body mass index, waist circumferences, WHR in schizophrenic patients. To assess the relationship between leptin, C-peptide and weight gain, glucose metabolism induced by clozapine. To investigate the mechanism and related factors of weight gain , glycometabolism abnormality induced by clozapine.Methods: sixty first-episode schizophrenic patients were randomly divided into two groups, which treated with clozapine andrisperidone respectively. The subjects were given either clozapine(75mg/d) or risperidone(1mg/d) for 3 days. Then gradually added to efficient dosage till day 14, maintained the dosage to 8 weeks. During the therapeutic periods, any other antipsychotics was not exerted except trihexyphenidyl (artane) which was necessary to be used for extrapyramidal symptoms (EPS).Before and after 8-week treatment, the fasting glucose, postprandial 1 , 2 hours blood glucose, c-peptid plasma leptin were measured. Body weight, body mass index (BMI) and waist-hip-ratio (WHR) were also measured for whole subjects in the other 2 weeks. All parameters were analyzed by SPSS10. 0 software.Results: (1)There were no significantly differences between thetwo groups' general index before patiens were treated. (2)After 8 weeks treatment, the weight, BMI, weight circumferences, WHR of the clozapine patients all increased greatly (P>0.05). Although the index of risperidone group had the increasing tendency, there were no significantly differences between pre-treatment and post-treatment(P>0.05). The accrescence amplitude of the above-mentioned four indexes all had significantly differences (P all<0. 05) between the comparison of the two groups. (3)At the end of 8 weeks the postprandial 1 , 2 hours blood glucose increased significantly compared with pre-treatment (P all<0.05), while the fasting glucose increased with no significant differences(P all>0. 05). But there were significant differences(P all<0. 05) between the comparison of the two groups in the accrescence amplitude of the fasting glucose, postprandial 1 , 2 hours blood glucose. The rate of impaired glucose tolerance (IGT) was higher in clozapine group (7/30,23.3%) than that in risperidone group (1/30, 3. 3%) (x2=3. 972, P<0. 05). ? At the end of 8 weeks, there were significant differences (P all<0.05) in the fasting, 1 hour, 2 hoursc-peptid compared with pre-treatment in clozapine group. The Opeptid horizontal curve of pre-treatment was all above post-treatment. The C-peptid horizontal curve of pre-treatment reached its peak at the time of 1 hour and the peak time of post-treatment delayed. While C-peptid and horizontal curve appeared no marked change compared with pre-treatment in risperidone group. ?At the end of 8 weeks, plasma leptin of the two groups had more significant differences (all P<0. 05) than those of pre-treatment, but the accrescence amplitude had no significant difference (all P>0.05) except for gender. ?BMI was positively correlated with WC, WHR, postprandial 2 hours blood glucose, and was inversely correlated with basement BMI. Plasma leptin was positively correlated with BMI, WC, WHR, while it was inversely correlated with gender. The accrescence amplitude of fasting C-peptide and the postprandial 1 hour C-peptide was correlated with blood glucose. The accrescence amplitude postprandial of the 2 hours C-peptide was correlated with BMI, plasma leptin. ?The high basement BMI, the postprandial 2 hours high blood glucose, the weight circumference, the postprandial 2 hours C-peptide were significant risk factors for IGT.Conclusions: Clozapine could easily induce schizophrenicpatients' weight gain and glucose metabolism abnormality. BMI or the postprandial 2 hours high blood glucose were the susceptible index of IGT which lead by clozapine. After the treatment of clozapine, the waist circumference' s quick amplification and postprandial 2 hours C-peptide' s high level may be the earlier period sign of IGT . In order to avoid the early intervention drug' s obesity and diabetes mellitus, it is necessary to monitor the body weight and glycometabolism index of the patients who take clozapine according to some index.