| Part Ⅰ:Changes and significance of plasma Asprosin in female patients with T2DMObjectives:Asprosin is a new protein hormone secreted mainly by white adipose tissue.Studies have shown that asprosin increases plasma asprosin levels in the blood of people with insulin resistance or obesity and mice.Asprosin is a hormone that activates AgRP neurons and increases food intake and body weight.However,its potential association with type 2diabetes mellitus(T2DM)remains unclear,especially in women with T2DM.The purpose of this study was to investigate the changes and significance of plasma asprosin in female patients with T2DM.Methods:1.We recruited 119 female subjects from February 2017 to November 2018 at the Second Affiliated Hospital of the Military Medical University(Xinqiao Hospital),including53 newly diagnosed patients with T2DM and 66 healthy women.The subjects in the two groups were divided into two subgroups:normal weight group(BMI<24kg/m~2)and overweight/obesity group(BMI≥24kg/m~2).2.Observing Indicators incude age,height,weight,waist circumference,hip circumference,waist-hip ratio,blood pressure,etc.Laboratory examination:plasma asprosin determination,fasting blood glucose,fasting insulin,triglyceride,cholesterol,high density lipoprotein,low density lipoprotein,liver,kidney function,HOMA-IR,HOMA-β,120 minutes insulin,insulin concentration-time curve(IAUC)area.3.Statistical analysis SPSS 22.0 was used for statistical analysis,measurements were denoted by?x±s,non-normal distribution measurements were denoted by median(quartile spacing);t-test was used for inter-group comparison;Spearman correlation analysis was used for the relationship between plasma asprosin level and various glycolipid metabolic indices and insulin resistance,and binary logistic regression was used to analyze plasma asprosin level and glycolipid metabolic indices.The relationship between plasma albumin level,glycolipid metabolism and insulin resistance parameters and T2DM was analyzed by binary logistic regression.The difference was statistically significant with P<0.05.Results:(1)The body mass index(BMI)and waist-hip ratio(WHR)in T2DM group were significantly higher than those in healthy group(P<0.05).In terms of glycometabolism,T2DM group had higher fasting blood glucose,glycosylated hemoglobin and HOMA-IR than healthy group(P<0.05).In terms of lipid metabolism,the levels of triglyceride,total cholesterol and low density lipoprotein in the T2DM group were significantly higher than those in the healthy group(P<0.05),and the levels of high density lipoprotein were significantly lower than those in the healthy group(P<0.05).(2)The plasma asprosin levels in healthy group,T2DM group,healthy subgroup and T2DM subgroup classified by BMI=24kg/m~2 were significantly higher than those in healthy group(P<0.05).In addition,the plasma asprosin level in overweight/obesity group was slightly higher than that in normal weight group,but no difference was observed between T2DM group and healthy subjects subgroup according to BMI.The plasma asprosin levels in the overweight/obese subgroups were higher than those in the normal weight subgroups.(3)Analysis of the correlation between plasma asprosin level and parameters of glycolipid metabolism and insulin resistance in all subjects According to Spearman correlation analysis,plasma asprosin levels were positively correlated with glycometabolism indicators(such as glycated hemoglobin,HOMA-IR),lipid metabolism indicators(triglyceride,total cholesterol),and general clinical indicators(waist-hip ratio,systolic blood pressure)after age adjustment(P<0.05).(4)The correlation between plasma asprosin level and glycolipid metabolic parameters in the subgroup of T2DM was analyzed.After adjusting the age factor,all subjects with T2DM were divided into two groups according to BMI=24kg/m~2.We found that plasma asprosin level was positively correlated with fasting blood glucose and glycosylated hemoglobin(P<0.05).After age correction,plasma asprosin level was positively correlated with HOMA-IR in T2DM group and normal weight group of diabetes mellitus(P<0.05),negatively correlated with OGTT-120 min insulin in normal weight group of diabetes mellitus and overweight HDL-C in diabetes mellitus(P<0.05).(5)Analysis of the relationship between plasma asprosin level and T2DM Logistic regression analysis showed that plasma asprosin level was an independent risk factor for T2DM after controlling for age,BMI,blood pressure,blood lipid,liver and kidney function(P<0.05).Conclusions:The potential role of plasma asprosin in healthy and T2DM patients was analyzed.Plasma asprosin is closely related to glycolipid metabolism and insulin resistance.Plasma asprosin is a potential predictor of T2DM in women.Part Ⅱ:The effects of GLP-1RA compared with Diane-35 on glycolipid metabolism and reproductive function in overweight PCOS patientsObjective: In this study,a 12-week randomized controlled clinical trial was conducted to compare the effects of metformin combined with glucagon-like peptide-1 receptor agonists(GLP-1RA)and metformin combined with Diane-35 on glycolipid metabolism and reproductive function in overweight PCOS patients in a short period of time(3 months).The changes of plasma asprosin levels were observed after treatment in the two groups.Materials and methods: All subjects underwent general biochemical examinations such as blood routine,liver and kidney function before admission.After obtaining informed consent,the remaining plasma 1 ml was collected from the laboratory and frozen in the refrigerator at-80 ℃ Patients with(BMI >24kg/m~2)or waist circumference(>85cm)were randomly divided into GLP-1RA group or Diane-35 group.Three months later,all subjects were re-examined for fasting blood sugar,fasting insulin,lipid,liver and kidney function,and plasma 1ml was retained for freezing storage at-80℃ refrigerator.PCOS subjects were randomly divided into GLP-1RA group(13 cases,metformin enteric-coated tablets 0.5g orally for 3/day + exenatide injection / linalopeptide injection)and Diane-35 group(12 cases,metformin enteric-coated tablets 0.5g orally for 3/day + Diane-351 tablets orally for 1/day).Before medication,the patients’ weight,waist circumference,menstrual history,blood pressure,glycolipid metabolism,sex hormones and liver fibrosis were assessed and blood samples were collected.The above indicators,glycolipid metabolism and sex hormone were re-evaluated in March and adverse events were recorded.Asprosin was determined by ELISA.The intra-batch CV was less than 6.5% and inter-batch CV was less than 9.8%.Result:(1)General clinical data Compared with before treatment,the body weight,waist circumference and diastolic pressure of GLP-1RA group decreased after 3 months of treatment(P < 0.05);the waist circumference of Diane-35 group decreased(P < 0.05);after 3 months of treatment,the body weight,waist circumference and diastolic pressure of GLP-1RA group were lower than those of Diane-35 group,and there was significant difference between the two groups(P < 0.05).(2)Biochemical Indicators Compared with before treatment,fasting blood sugar,30 minutes insulin,liver hardness and fat attenuation in the two groups decreased significantly after 3 months of treatment(P < 0.05),while GLP-1RA group was significantly lower than Diane-35 group(P < 0.05).Compared with before treatment,fasting insulin and plasma asprosin in the two groups decreased after 3 months of treatment,but no significant difference was observed between the two groups(P >0.05).Compared with before treatment,there was no significant difference in triglycerides between the two groups after 3 months of treatment(P > 0.05).(3)Sex Hormone Indicators Compared with before treatment,the serum luteinizing hormone level of the two groups decreased significantly after 3 months of treatment.The luteinizing hormone level of GLP-1RA group was lower than that of Diane-35 group,and there was a significant difference between the two groups(P < 0.05).After 3 months of treatment,the estradiol level in GLP-1 RA group was higher than that before treatment(P <0.05);After 3 months of treatment,there was no significant difference in testosterone level between the two groups(P >0.05).(4)Menstrual Cycles In GLP-1RA group,menstrual cycle was established in 12 cases(92.3%)and in Diane-35 group,menstrual cycle was established in 5 cases(41.7%).After 3 months of treatment,the number of menstrual cycles in GLP-1RA group was higher than that in Diane-35 group,with statistical significance(P <0.05).(5)Safety evaluation during treatment: the most common adverse reaction of GLP-1RA was gastrointestinal discomfort.In this study,10 patients(25%)had nausea,diarrhea and dyspepsia,but the duration of symptoms was short.It occurred mainly in the first week of treatment,and then the incidence decreased significantly with the prolongation of treatment time.There was no severe hypoglycemia(blood sugar <3.9 mmol/L).None of the subjects had abnormal liver and kidney functions.Conclusion: Overweight/obese PCOS patients mainly have metabolic disorders.GLP-1RA combined with metformin can effectively reduce the weight of overweight or obese PCOS patients,improve glycolipid metabolism and establish regular menstrual cycle.Plasma asprosin is associated with hyperinsulinemia,which can improve PCOS by reducing hyperinsulinemia and thereby stimulating ovarian follicular membrane cells.Plasma asprosin may play a role in the pathogenesis of PCOS and provide a possible intervention target for the treatment of PCOS patients. |
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