Secretion of glucagon and glucagon-like peptide-1 in different glucose tolerance status during pregnancy / 中华临床营养杂志

ABSTRACT

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.