Characteristics Of Glycemic Fluctuation In Gestational Diabetes Mellitus Different Fasting Plasma Glucose Level And The Influence Of Diet Therapy The Glucose Variability

[BACKGROUND]Gestational hyperglycemia includes diabetes in pregnancy and hyperglycemia first detected during pregnancy. The new diagnostic criteria for hyperglycaemia first-detected in pregnancy recommended by the World Health Organization (WHO) in 2013 includes diabetes mellitus in pregnancy(DIP) and gestational diabetes mellitus(GDM). The diagnostic criteria for DIP consistents with diabetes recommended by the World Health Organization (WHO) in 1999.The data of IDF shows that the global prevalence of hyperglycaemia in pregnancy is 6.9%, and the incidence is as high as 7.0% in our country. Gestational diabetes mellitus (GDM) was defined as any degree of glucose intolerance that was first recognized or discovered during pregnancy and it is the most common metabolic disease during pregnancy.The incidence of it will continue to rise. Due to the diagnostic methods and criteria has not been fully unified,so the morbidity of GDM ranges from 1%～14%.Xie Xing et al point out that with the change of dietary structure and the reset of diagnostic criteria, the diagnostic rate of GDM is continue to rise and the morbidity ranges from 1%～ 5% in our country. HAPO study testified that Gestational hyperglycemia is the most common medical complications during pregnancy, it often result in adverse perinatal outcomes,such as large for date infant,pre-eclampsia,gestational hypertension,preterm delivery,shoulder dystocia,birth trauma,cesarean section,neonatal hypoglycemia,neonatal hyperbilirubinemia and so on, even may cause pregnant women and there offspring membolic disorder in long term.Glucose fluctuations as one of the sugar metabolic disorder takes part in the development of diabetic vascular complications by increasing oxygen free radicals and vascular endothelial dysfunction.Theglucose variability and variation of GDM is more significant,and it is related to the islet B cell function defect and insulin resistance. With the increase of gestational age, the increased hormones secreted by pituitary and placental result in deepening physiological insulin resistance during the middle-late gestation, this pregnancy-related insulin resistance is met with a corresponding increase by two-to threefold in pregnancy in insulin secretion.In addition to physiological insulin resistance, chronic insulin resistance exist in GDM to make insulin sensitivity decreased further. when β cells dysfunction that insulin secretion fail to keep pace with the demand during pregnancy,it lead to gestational hyperglycemia.Some studies have shown that during breastfeeding, women with a recent history of GDM, still normotolerant by OGTT 1 year after delivery,had higher daily glycemic profiles and higher variability than women who were normotolerant during pregnancy.This means that women with GDM still exist islet B cell function defect and insulin resistance during postpartum, even increase the risk for type 2 diabetes mellitus in long term.Blood glucose monitoring is the one of methods in diabetes treatment, but the traditional detection of fingertip blood and venous blood glucose only reflect instantaneous blood glucose values, it can not reflect the characteristics and regular of linear glucose. With the development of blood glucose monitoring technology, continuous glucose monitoring(CGM) which is similar to "Holter" minimally invasive monitoring system is increasing mature. It is the most advanced technology of blood glucose monitoring in currently,it could obtain signal from the probe every 1 0 seconds, and save the average of the signal every 5 minutes, a total of 288 blood glucose values can be recorded a day and continuous monitor patients’blood glucose levels for 72 hours.The adventage of CGMS is discovering the hyperglycemia and hypoglycaemiaevents which could not found by traditional blood glucose monitoring, especially the postprandial hyperglycemia and asymptomatic hypoglycemia in night.lt helps to analyze the changes of blood glucose fluctuations in tendency, amplitude, frequency, time,reasons and so on comprehensively.GDM is similar to other forms of diabetes which diet palys a key role in the management of it.Considering the particularity of pregnancy,we don’t use any drug or insulin to intervent generally, unless the illness is very seriously. However, the overall elevated of blood glucose values and blood glucose fluctuations are associated with poor perinatal outcomes closely.The suggestions of American Diabetes Association (ADA) on nutritional therapy guidelines for the diabetes is that all patients diagnosed as GDM should ask the advicement of nutritionist to set specific allocation of nutrients which is according to its current dietary patterns, favorites and the goal of blood glucose control,and accept medical nutrition therapy.By using CGM to monitor GDM last for more than 120 hours,this study analyzed and discussed the characteristics of glycemic fluctuation in gestational diabetes mellitus with different fasting plasma glucose level,the relationship between pregnancy outcome and different fasting plasma glucose level, and the influence of diet therapy on the glucose variability. To provide the partial clinical data for managing the glucose of gestational period.[objectives]To discuss the characteristics of glycemic fluctuation in gestational diabetes mellitus with different fasting plasma glucose level,the relationship between pregnancy outcome and different fasting plasma glucose level, and the influence of diet therapy on the glucose variability by continuous glucose monitoring system (CGMS), making the clinicians manage blood sugar better in GDM during the perinatal period, keeping blood sugar levels in normal of the whole pregnancy, reducing the occurrence of adverse pregnancy outcomes finally.[Methods]1. Resaerch subjects:A total of 316 patients who diagnosed as gestational hyperglycemia in prenatal examination from October in 2010 to July in 2015,were dieting for a week in outpatient department and still not reach the glycemic control standard.They hospitalized in the Endocrinology and Metabolism Department at Nanfang Hospital in Guangzhou and used the continuous glucose monitoring system (CGMS)made to monitor the blood glucose level voluntarily. Pregnancy women who with diabetes, hypertension, other endocrine and metabolic diseases, Other liver and kidney diseases smoking and alcohol and twin pregnancy need to be excluded.Finally, the actual number of subjects adopted to the American Diabetes Association(ADA) standards published in 2015 was 173. The mean age is(31.6+4.8)years old and the mean gestational weeks is (27.69+4.28)weeks.2. Resaerch methods:Based on the fasting plasma glucose(FPG) of OGTT test,the patients were divided into 3 groups:group A with the normal FPG(FPG<5.1mmol/L, n=72),group B with FPG range from 5.1mmol/L to 6.1mmol/L(5.1≤FPG<6.1mmol/L,n=67), group C with FPG equal or more than 6.1mmol/L(FPG≥6.1mmol/L,n=34). Take the survey and the basic laboratory tests of the pregnancy women, continuous glucose monitoring system (CGMS) was used to monitor the blood glucose level, to analyze the indicators of the clinical and the CGMS simultaneously.[Resultsl]1. General clinical data:There were no significant differences in age、 gestational age、TG、fasting plasma c-peptide in three groups (P<0.05); with the FPG of OGTT test increasing,the 1 hour and 2 hour blood glucose after take suger were higher.TheHbAIC、BMI、SBP、DBP、the insulin resistance (HOMA-IR) in group B and group C were higher than group A (P<0.05);then the LDL-C、CHOL、HDL-C and the islet b-cell function(HOMA-β) in group C were lower than group A(P<0.05). FPG was significantly positive correlation with BMI、SBP、DBP、TG、HbA1C while there was significantly negative correlation between that and HDL-C (P<0.05).2. The parameters of CGMS:(1)、The characteristics of blood glucose in three mealsThe mean blood glucose before breakfast and the 1 hour and 2 hour mean blood glucose after breakfast in group B and group C were higher than group A (P<0.05),while the mean blood glucose before lunch and dinner and the 1 hour and 2 hour mean blood glucose after lunch and dinner in group C were higher than group A and group B(P<0.05). The blood glucose peak of breakfast and lunch in group C was higher than group A and group B (P<0.05),while the blood glucose peak of dinner in group C was higher than group A(P<0.05). The blood glucose peak of breakfast was higher than lunch and dinner (P<0.05) in three groups, while there were no significant differences in the time to peak of three meals in three groups(P>0.05). There were no significant differences on the incidence of hypoglycemia in three groups(P>0.05).(2)、The parameters of blood glucose fluctuation①、The MAGE、MBG, PT(BG>6.7mmol/L)、AUC(BG>6.7mmol/L)、Daytime MBG(6:30-23:30) and nighttime MBG(23:30-6:30) in group C were higher than group A and group B (P<0.05),while there were no significant differences in the SD、 FPG-CV and MODD in three groups(P>0.05).②、FPG was significantly positive correlation with MBG、MAGE、LAGE、 PT、AUC、Daytime MBG and nighttime MBG(P<0.05).3、Diet therapy(1)、The rate of insulin utilization and success rate of Diet treatmentThe the success rate of Diet treatment in group A was 90.3%, and the insulin utilization was 9.7%. The success rate of Diet treatment in group B was 83.1%,and the insulin utilization was 26.9%. The success rate of Diet treatment in group C was 58.8%,and the insulin utilization was 70.6%. FPG was the predictor for the necessity of insulin treatment.,and PT was the predictor for the success rate of Diet treatment.(2)、The parameters of CGMS after diet therapy①、The characteristics of blood glucose in three mealsAfter treatment with diet,the 2h mean blood glucose after breakfast and the blood glucose peak of breakfast、the MAGE、SD in group A were lower than before diet, and the mean blood glucose at night was higher than before diet (P<0.05).The 2h mean blood glucose after breakfast and the PT、SD、AUC、the mean blood glucose during the day in group B were lower than before diet (P<0.05). There were no significant differences of the characteristics of blood glucose in three meals and blood glucose fluctuation in group C after diet therapy (P>0.05).4、Pregnancy outcomesThere were no significant differences in delivery time, birth weight, neonatal blood sugar, neonatal bilirubin, cesarean section rate, the incidence of neonatal hypoglycemia and the incidence of macrosomia(P>0.05).The fasting plasma glucose with GDM patients is in relationship to neonatal blood sugar and cesarean section rate(P<0.05). MAGE、PT and 1h glucose after take suger were the risk factors for macrosomia,and the fasting plasma glucose was the independent factor for cesarean.[CONCLUSIONS]1、CGMS could provide integrative glucose profiles information.It can find many hypoglycemia and hypoglycemia which self blood glucose monitoring is not easy to detect,especially the postprandial hyperglycemia and night asymptomatic hypoglycemia.It helps to comprehensively analyze the tendency of changes in blood glucose fluctuations, amplitude, frequency, time, the reasons, and so on.2、Compared to GDM patients with normal fasting glucose, the one with abnormal fasting glucose was higher in BMI, SBP, DBP, FINS and HbAlC level. With the increasing of fasting glucose levels,the indicators of blood glucose fluctuation,such as MBG, MAGE, LAGE, PT, AUC, MBG during the day and MBG during the night were also increased.3、MAGE、PT and 1 hour blood glucose after take suger were the risk factors for macrosomia,and the fasting plasma glucose was the independent factor for cesarean.4、With the fasting glucose level going,the insulin utilization rate increased, while the success rate of diet treatment reduced. PT (BG>6.7mmol/L) was the predictor for the success rate of Diet treatment,and FPG was the predictor for the necessity of insulin treatment.5、When FPG≥6.1mmol, the blood glucose fluctuation of it was bigger, the time of high blood glucose lasted longer, the insulin resistance of it was more obvious and the islet B cell function was damaged more severely. Due to the bad effect of diet treatment,it was recommended to use insulin therapy as soon as possible. Trying to keep blood sugar levels in normal of the whole pregnancy, and to reduce the occurrence of adverse pregnancy outcomes finally.