Objective To evaluate the value of continuous glucose monitoring system (CGMS) in the gestational patients with impaired glucose regulation. Methods The glucose level in the subcutaneous tissue was monitored by CGMS for 3 days in 6 patients with gestational diabetes mellitus (GDM) and 6 patients with gestational impaired glucose tolerance (GIGT). The fluctuation coefficient of blood glucose, percentage of hyperglycemic time, and percentage of hypoglycemic time were calculated. Results As shown by CGMS, the fluctuation coefficient of blood glucose, mean glucose level, percentage of hyperglycemic time, percentage of hypoglycemic time, mean fasting blood glucose, and mean postprandial blood glucose (PBG) levels were not significantly different between GDM group and GIGT group (P ＞ 0. 05). The time for reaching the peak PBG level ranged 90-120minutes in both two groups (P ＞ 0. 05). No sensor-related adverse events were noted. Conclusions It is safe to apply CGMS sensor in pregnant women. The blood glucose profiles are comparable between GDM and GIGT patients by CGMS; therefore, control of blood glucose should be equally strict in patients with GIGT as those with GDM.

Objective To study the pharmacokinetics and pharmacodynamics of the 40/60 premixed recombinant human insulin injection preparation,and to compare with 30/70 preparation,regular insulin,and neutral protamine Hagedorn (NPH).Methods In this positive control,single dose,open label,Latin square crossover study,20 male healthy volunteers were recruited from May 2006 to March 2007,and divided into four groups.On 4 test days,40/60 preparation,30/70 preparation,regular insulin,and NPH were administered to each of the 4 groups,the interval was 7-70 days before 2 test days.The pharmacokinetics and pharmacodynamics were evaluated by euglycemic glucose clamp technique.Results According to the analysis of variance,there were statistically significant differences in pharmacokinetics and pharmacodynamics of the 4 insulin formulations between the 4 groups (all P ＜ 0.05).For the 40/60 premixed recombinant human insulin,the pharmacokinetic parameter time to peak (Tmax) and mean retention time (MRT) were (105.00 ±24.33) minutes and (321.77 ± 56.29) minutes,respectively;the glucose-lowering effects reflected by the pharmacodynamic parameter Tmax and MRT were (167.75 ± 26.48) minutes and (248.33 ± 14.96) minutes,respectively.Compared with 30/70 premixed recombinant human insulin,40/60 preparation showed no significant differences in the pharmacokinetics parameters of blood insulin concentration,including peak concentration [(91.67 ± 13.03) mU/L vs.(84.96 ± 14.75) mU/L,P =0.119],Tmax [(105.00 ± 24.33) minutes vs.(122.25 ± 39.35) minutes,P =0.128],MRT [(321.77 ± 56.29) minutes vs.(332.12 ± 49.20) minutes,P =0.645] and area under the curve in 0-16 hours [AUCIns 0-16,(24 918 ± 6 610)h · mU/L vs.(26 768 ± 8 032)h· mU/L,P=0.084];however,statistically significant differences were observed in AUCIns0-4 [(16 991 ± 3 673) h · mU/L vs.(12 407 ± 3 441) h · mU/L,P =0.042] and AUCIns 0-8 [(23 283 ± 4 939) h · mU/L vs.(19 397 ±5 314)h · mU/L,P =0.046].Pharmacodynamic parameters showed no statistically significant differences (all P ＞ 0.05).Compared with 30/70 premixed insulin,the relative bioavailability of 40/60 premixed insulin was (118.9 ± 35.9) ％,and the relative biological effectiveness was (106.6 ± 35.2) ％.There was no clinically significant abnormalities in the safety indexes before and after the tests.No hypoglycemic events,allergic reactions,or local injection adverse reaction occurred in this trial.Conclusions The 40/60 premixed recombinant human insulin preparation demonstrated different properties in insulin absorption in 8 hours after injection compared with the 30/70 preparation,mainly because of the difference in proportions of short-and intermediate-acting insulin in the mixture.This new premixed insulin may provide a new option for personalized diabetes management.

Objective To study the pharmacokinetics and pharmacodynamics of recombinant human insulin preparations SciLin TM R and Humulin (R) R,and to evaluate their bioequivalence in Chinese healthy volunteers.Methods In this positive control,single dose,open label,randomized cross-over study,20 male healthy volunteers were recruited from March to October 2007,and tested on two experimental days with an interval of 7-14 days.The volunteers were divided into two groups with a random number table,one group was injected with SciLin TMR for the first time and Humulin (R) R for the second time,the other group was injected with the opposite.The pharmacokinetics and pharmacodynamic properties were evaluated by euglycemic glucose clamp study.Results Time to peak concentration [Tmax,(105.8 ± 19.1) minutes vs.(103.5 ± 18.1) minutes,P =0.389) and time to maximum glucose infusion rate [TGIRmax,(132.8 ± 16.8) minutes vs.(132.8 ± 18.6) minutes,P =0.697] for SciLin TMR and Humulin(R) R were similar.The relative bioavailability of SciLin TMR was (102.2 ± 7.6) ％,and the relative biological effectiveness was (107.4 ± 18.8) ％.The 90％ confidence interval(CI) of peak concentration(Cmax) and area under the curve of blood glucose concentration at 0-10 hours (AUCIns 0-10) of SciLin TM R were 99.32 ％-102.62 ％ (equivalent range 70％-143 ％) and 98.98 ％-104.99 ％ (equivalent range 80％-125％),respectively;90％ CI of the maximum glucose infusion rate (GIRmax) and AUCGIR0-10 were 97.36％ ～ 103.49％ (equivalent range 70％-143％) and 98.72％-113.54％ (equivalent range 80％-125％),respectively,indicating that SciLin TMR and Humulin (R) R was bioequivalent.There was no clinically significant abnormalities in the safety indexes before and after the tests.During the trial,no hypoglycemic events,allergic reactions,or local injection adverse reaction occurred.Conclusion The studied recombinant human insulin preparation SciLin TMR may be bioequivalent as Humulin (R) R.

Objective To establish the technique of hyperinsulinemic euglycemic clamp and to study the reference value of insulin sensitivity index in healthy Chinese. Methods According to the feedback mathematical model developed by DeFronzo, the technique of hyperinsulinemic euglycemic clamp was used in 90 healthy Chi- nese [ male:female =71 = 19; age; (28. 3±6. 1) years; body mass index (20. 9±1.5) kg/m2 ] to study die glu-cose metabolized rate. Blood samples were obtained at timed intervals in the fasting state and during the clamp for the measurement of glucose, insulin and C peptide. Results During the clamp tests, the blood glucose levels were con-trolled within 10% of target value. The coefficient of variation of glucose levels was 3. 8% 0.1%. In the steady state, the insulin sensitivity index (glucose metabolized rate, M value ) was (7.78±2.30) mg· kg-1 min-1, which was distributed normally. The lowest quartile of M value was 6. 286 mg·kg -1 min-1'. The coefficient of variation of M value was 9.4%±2.8%. Conclusion The technique of hyperinsulinemic euglycemic clamp and the reference value of insulin sensitivity index in healthy Chinese are successfully established in our center.

emic euglycemic clamp quantitively.

Objective To compare two different dumping cooking methods (boiling vs.frying) in their effect on postprandial glucose level in diabetic patients using continuous glucose monitoring (CGM).Methods 10 type 2 diabetes mellitus (T2DM) in-patients in the Department of Endocrinology of Peking Union Medical College Hospital between February and May 2011 were enrolled,whose fasting and preprandial glucose levels were controlled with a insulin pump.On day 2 and day 4 in the study period,the patients were given fried dumplings and boiled dumplings for lunch respectively,with the same nutrient contents.The starch digestibility of these two kinds of dumplings were compared using in vitro resistant starch digestion,measuring the concentrations of rapidly digestible starch,slowly digestible starch,and resistant starch.CGM was used to record blood glucose changes,in order to evaluate glycemic effect of these two dumpling cooking methods on postprandial glucose levels at 9 time points (0,15,30,60,90,120,150,180,and 240 minutes),peak blood glucose,and area under the curve (AUC) in 4 time periods (0-60,63-120,123-180,and 183-240 minutes).Results The percentage of rapidly digestible starch was remarkably lower in fried dumplings than in boiled dumplings (30.8％ vs.77.0％),but the content of slowly digestible starch in fried dumplings was higher than that in boiled ones (63.7％ vs.20.7％),and the content of resistant starch in both dumplings were similarly low (1.9％ and 2.3％).The average time to the peak glucose value was shorter in fried dumplings compared with boiled dumplings [(93 ± 53) minutes vs.(156 ± 61) minutes,P =0.02],but the average glucose levels at all the 9 time points and the AUC in all the 4 time periods were not significantly different (all P ＞ 0.05).Conclusions Compared with fried dumplings,boiled dumplings show faster starch digestion,but long time to the peak postprandial glucose level.Fried dumplings may raise the glucose level faster than boiled dumplings do in T2DM patients.

Objective To explore the relationship between glycated albumin ( GA ) in 2 consecutive months and hemoglobin A1c ( HbA1c) in diabetes patients.Methods Totally 100 consecutive patients with main diagnosis of diabetes mellitus were enrolled retrospectively from April 2015 to January 2016 in outpatient clinic of endocrinology of Peking Union Medical College Hospital, who had undertaken GA tests every 4 weeks for 2 successive months and had HbA1c test in the second month.GA was measured with liquid enzymatic method. HbA1c was measured by ion-exchange high performance liquid chromatography.The relationship between HbA1c and GA for the 2 successive months was determined.Results A total of 85 patients were enrolled.The regres-sion equation between HbA1c (y) and average GA (j) for successive 2 months was y=3.187+0.218j (adjusted R2 =0.520, P=0.000), which showed a similar effect as the regression equation for HbA1c and the levels of GA tested for the 2 successive months (adjusted R2 =0.514, P=0.000), and both had more significant regressive effect than the regression equation for HbA1c and single measurement of GA (adjusted R2 =0.392, P=0.000). Conclusions The regressive effect between HbA1c and GA (or the average of GA) in successive 2 months is bet-ter than that with single measurement of GA, hence could better predict HbA1c in clinical practice.

Objective To evaluate the clinical and biochemical characteristics of pregnant women with different glucose tolerance status,and their secretion characteristics of insulin,glucagon and glucagon-like peptide-1 (GLP-1) after oral glucose challenge.Methods We analyzed 74 cases pregnant women with positive results of 50 g glucose challenge test in 24-28 gestational weeks,who received regular obstetrical follow-up in Peking Union Medical College Hospital from January 2009 to June 2012.A further 100 g oral glucose tolerance test (OGTT) was performed,based on which the included women were divided into three groups,namely gestational diabetes mellitus (GDM) group (n =25),impaired glucose tolerance (IGT) group (n =25) and normal glucose tolerance (NGT) group (n =24).The general clinical data and biochemical indexes of the three groups were compared,and the indexes about insulin resistance and the function of pancreatic islet beta cells were calculated.Glucose,insulin,glucagon and GLP-1 were measured in OGTT.The secretion characteristics of each of these hormones and their correlation with other indicators were evaluated.Results Compared with the NGT group,the GCT [(9.21 ±0.75) mmol/L vs.(8.52 ±0.50) mmol/L,P ＜0.05] and glycosylated hemoglobin A1c [(5.39±0.34)％ vs.(5.18 ±0.20)％,P＜0.05] were significantly higher in the GDM group.In OGTT,the area under curve (AUC) of glucose in the GDM group was significantly higher than that inthe IGT group and NGT group [(26.58 ±2.02) mmol/(L · h) vs.(23.20 ± 1.51) mmoL/(L · h),(26.58 ± 2.02) mmol/(L · h) vs.(19.84 ± 1.95) mmol/(L · h),both P ＜ 0.05].The peak values of insulin secretion in the GDM group and IGT group were delayed to 2 hours after OGTT.The 3-hour insulin level in the GDM group was significantly higher than that in the NGT group (P ＜ 0.05).Compared with the NGT group,the glucagon levels in each time point after OGTT and the AUC of glucagon levels were reduced in the GDM group and the IGT group,but with no significant differences.The peak glucagon levels in the 3 groups all appeared at 3 hours after OGTT.The GLP-1 levels in each time point of OGTT were gradually increased from the NGT group to the IGT group to the GDM group,but no significant differences were found.The peak value of GLP-1 level was presented at 1 hour after OGTT in the NGT group and the IGT group and at 2 hours after OGTT in the GDM group.The valley values of GLP-1 level in the 3 groups all appeared at 3 hours after OGTT.In comparison with the NGT group,the ratios of GLP-1 to blood glucose levels (GLP/BG) at 1-hour and 2-hour were significantly decreased in the GDM group (P ＜ 0.05).The AUC of glucagon levels in OGTT were negatively correlated with fasting blood glucose (r =-0.287,P =0.013) and 1-hour glucose levels (r =-0.266,P =0.022) in OGTT and positively correlated with insulin secretion sensitivity index (ISSI) (r =0.297,P =0.010) and HOMA-β (r =0.236,P =0.043).Moreover,the AUC of GLP-1 levels in OGTT was negatively correlated with the levels of C-reactive protein (r =-0.264,P =0.035).The AUC of GLP/BG in OGTT was positively correlated with ISSI (r=0.406,P＜0.001).Conclusions Pregnant women with GDM and IGT in the second trimester have insulin resistance and dysfunction of pancreatic islet β cells.Potential GLP-1 resistance and inadequate secretion may exist in GDM patients.GLP/BG may be a better parameter to evaluate the secretion function of L cells in pregnancy and an effective parameter to estimate the compensatory function of pancreatic β cells indirectly.Glucagon levels may not start to change obviously before 28 gestational weeks.

Objective To evaluate clinical features,insulin sensitivity,and serum adipocytokines levels in pregnant women with different glucose tolerance status and to investigate the possible serum predictive biomarkers of gestational diabetes mellitus (GDM).Methods We included 74 pregnant women with positive results of 50 g glucose challenge test (GCT),who received regular obstetrical follow-up in Peking Union Medical College Hospital from January 2009 to June 2012.A further 100 g oral glucose tolerance test was performed in 24-28 gestational weeks,based on which the 74 pregnant women were divided into GDM group (n =25),impaired glucose tolerance (IGT) group (n =25) and normal glucose tolerance (NGT) group (n =24).The clinical data were recorded in detail.Serum fibroblast growth factor (FGF)-19,FGF-21,visceral adiposespecific serine protease inhibitor (vaspin),leptin,insulin-like growth factor binding protein-1 (IGFBP-1),and adiponectin levels of the 3 groups were measured by enzyme-linked immunosorbent assay (ELISA) and compared.The associations of these adipocytokines with the patients' baseline data and metabolic indexes were analyzed.Results The blood glucose after GCT and glycosylated hemoglobin A1c in the GDM group were significantly higher than those in the NGT group [(9.21 ±0.75) mmol/L vs.(8.52 ±0.50) mmol/L,P ＜0.05;(5.39 ± 0.34) ％ vs.(5.18 ± 0.20) ％,P ＜ 0.05],but not significantly different from those in the IGT group [(9.14 ± 0.64) mmol/L,P ＞ 0.05;(5.28 ± 0.28) ％,P ＞ 0.05].Age,systolic blood pressure and diastolic blood pressure in the first trimester,pre-gestational body mass index (BMI),increment of BMI during pregnancy,serum total cholesterol,triglyceride,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,and C-reactive protein levels in the three groups showed no significant differences (all P ＞0.05).From the NGT group to the IGT group to the GDM group,the area under curve of blood glucose (AUCBG) [(19.84±1.95),(23.20±1.51),(26.58±2.02) mmol/(L · h)] and AUC of insulin (AUCINS) [(1.84± 0.91) ×103,(1.85 ±1.15) ×103,(2.49 ±1.36) ×103 pmol/(L · h)] both gradually increased.Compared with the NGT group,the GDM group had significantly higher HOMA-IR [3.0 (1.5,5.2) vs.2.5 (1.5,3.4),P ＜0.05] significantly lower HOMA-β [230.5 (144.6,311.6) vs.235.6 (168.1,350.0),P ＜ 0.05].Among the GDM,the IGT,and the NGT groups,there were no significant differences in serum FGF-19 [(284.42±78.16),(268.17 ±72.97),(283.86 ±79.74) ng/L],FGF-21 [(798.16±273.57),(882.43 ±322.17),(842.75 ±343.01) ng/L],vaspin [(22.36 ±7.27),(23.53 ±7.90),(22.63±9.11) μag/L],leptin [(5.51 ± 1.44),(5.58 ± 1.58),(5.48 ± 1.47) μg/L],adiponectin [(798.85 ± 255.14),(863.44 ± 252.18),(828.36 ± 249.32) μg/L] and IGFBP-1 [(40.44 ± 16.41),(49.57±12.60),(43.80±16.58) μg/L] levels (all P＞0.05).Conclusions There are no significant differences of a variety of adipocytokines in pregnant women with different glucose tolerance status,and no effective serum predictors of GDM are found.The effect of adipocytokines in the pathogenesis of GDM remains to be further investigated.

Objective To evaluate clinical features,insulin sensitivity and β-cell function of pregnant women with different glucose tolerance status,so as to identify the possible risk factors for adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM).Methods We retrospectively analyzed the clinical data of 360 pregnant women with positive results of 50 g glucose challenge test who received antenatal care and admitted for delivery in the period from January 2009 to June 2012 in Peking Union Medical College Hospital.According to the result of 100 g oral glucose tolerance test (OGTT),the 360 women were divided into GDM group (n =83),impaired glucose tolerance (IGT) group (n =75),and normal glucose tolerance (NGT) group (n =202).The blood glucose level in all those women was controlled in normal range for gestational period.We compared the general clinical data,biochemical indexes,insulin resistance index,insulin sensitivity index,function index of islet β-cell,first-and second-phase insulin secretion,insulin secretion-sensitivity index as well as the pregnancy outcomes of the 3 groups,analyzing the possible risk factors for adverse pregnancy outcomes in women with GDM.Results Compared with the NGT group,the pregnant women in GDM group were older [(33.1 ± 3.7) years vs.(31.7 ± 3.4) years,P =0.008],had higher systolic blood pressure [(115.8 ± 9.7) mmHg vs.(111.4 ± 13.5) mmHg (1 mmHg =0.133 kPa),P =0.031] and diastolic blood pressure in first trimester [(75.4 ±9.0) mmHg vs.(71.8 ±8.8) mmHg,P =0.010],higher positive rate of family history of diabetes in first-degree relatives (37.3％ vs.22.3％,P =0.012),positive rate of insulin therapy (10.8％ vs.0％,P =0.001),serum triglyceride level [(2.8 ±0.9) mmol/L vs.(2.3 ±0.9) mmol/L,P =0.001],free fatty acid level [(486.7 ± 137.6) μmol/L vs.(438.1 ± 140.7) μmol/L,P =0.033],and C-reactive protein level [(5.7 ± 4.3) mg/L vs.(3.6 ± 3.0) mg/L,P =0.001].The GDM group had a larger pre-pregnancy body mass index [(22.6 ± 2.9) kg/m2] than that in IGT group [(21.3 ± 2.7) kg/m2] (P =0.049) and NGT group [(21.2 ±2.8) kg/m2] (P =0.003).In the order from NGT to IGT to GDM group,the hemoglobin A1c [(5.2 ± 0.3) ％ vs.(5.3 ± 0.3) ％ vs.(5.4 ± 0.3) ％,P =0.001,P =0.007],the areas under curve of glucose [(20.4±2.0) mmol · h/L vs.(22.9 ± 1.5) mmol · h/L vs.(26.9 ±2.1) mmol · h/L,both P=0.001] and the areas under curve of insulin [(1.7 ±0.9) × 103 pmol · h/L vs.(2.1 ± 1.1) × 103 pmol · h/L vs.(2.7±1.3) ×103 pmol · h/L,P=0.001,P=0.007] increased gradually,while insulin sensitivity index (88.1 ± 52.1 vs.80.0 ± 30.6 vs.50.0 ± 24.1,P =0.001,P =0.014) and insulin secretion-sensitivity index (134 507.0 ± 43 291.0 vs.102 542.0 ± 15 291.0 vs.77 582.0 ± 20 764.0,both P =0.001) decreased gradually.The insulin resistance index in the GDM group (3.3 ± 2.2) was significantly higher than that in IGT (2.2 ± 1.0) and NGT groups (3.0 ± 1.1) (both P =0.001).The function of β-cell,first-and second-phase insulin secretion were not significantly different among the 3 groups.Compared with the NGT group,pregnant women with GDM had shorter gestational age [(38.8 ± 1.1) weeks vs.(39.4 ± 1.1) weeks,P=0.004] and higher incidence of adverse pregnancy outcomes (44.6％ vs.21.8％,P =0.001).Seven risk factors predicting adverse pregnancy outcomes in women with GDM were identified,including pre-pregnancy body mass index (P=0.017),0-,1-,and 2-hour blood glucose in 100 g OGTT (P=0.036,P=0.009,P=0.004),3-hour insulin (P =0.014),and hemoglobin A1 c (P =0.002) and C-reactive protein (P =0.005) in second trimester,among which 1-hour blood glucose displayed the highest coefficient (OR =2.767).Conclusions Pregnant women with GDM have elevated blood pressure,dyslipidemia and increased inflammatory cytokine C-reactive protein.Women with GDM and IGT both show insulin resistance and β-cell dysfunction,and these impairments are more severe in women with GDM.Higher pre-pregnancy body mass index and blood glucose levels during pregnancy are associated with adverse pregnancy outcomes in women with GDM.