Determinação da grelina acilada e dos ácidos graxos livres durante teste de tolerância oral à glicose na gestação normal e na gestação complicada por diabetes gestacional

Abstract

The gestational diabetes is admittedly an insulin resistant state. It is thus an excellent model to study the pattern of many metabolic values that show differences in insulin resistants states. These differences occur during both the fasting state and the postaprandial state. By this reason, the oral glicose tolerance test (OGTT) in gestational diabetes can be used with the purpose of studding insulin resistance. The objective of our first study is to analyze the acylated ghrelin behavior during OGTT in pregnant women with and without glycemic metabolism disturbance. Ghrelin is an amino acid hormone predominantly produced by stomach, and its receptor GHS-R1a is expressed in pituitary and hypothalamus. However, to be bound, ghrelin has to be acylated in one of its serines residues changing to active form. It has a typical circadian rhythm in healthy human with raise in pre-prandial levels and decline after meals. This postprandial suppression is blunted in pathological conditions with insulin resistance as diabetes and polycystic ovary syndrome. In glycemic metabolism, acylated ghrelin seems to exert a tonic inhibitory regulation on glucose stimulated insulin secretion, and raises hepatic glucose output. These actions are supposed to be opposing by des-acyl ghrelin or non-active ghrelin. Thus, it is extremely important to analyze acyl ghrelin action, pattern and control in normal glycemic metabolism and in gestational diabetes. For that purpose, a total of 41 women were recruited: 28 pregnant women underwent a routine oral glucose tolerance test (75g-2h-OGTT) after the 24th week of pregnancy, while another group of 13 non pregnant healthy volunteer women, matched to age and BMI, underwent the OGTT (control group, NOR). The pregnant women were assigned to two groups according to ADAs fourth Workshop Conference Criteria for Gestational Diabetes recommendations fifteen pregnant women with gestational diabetes (GDM) and 13 healthy pregnant women (GES). Blood samples were drawn at baseline and 60, 120 min. after glucose overload for the determination of glucose, insulin and acylated ghrelin. Acylated ghrelin did not show statistical difference in baseline values among groups. None of the groups show significant suppression of acylated ghrelin during OGTT, when compared with its basal acylated ghrelin levels. However, when we compared the acylated ghrelin curves during OGTT, we found statistical difference among the curves by two way ANOVA with repeated measures (p = 0.018). When we used Holm-Sidak test to detect which group were different, a significant lower values occurred in GDM at 60 minutes, if compared to GES (p = 0.006). We have showed, for the first time, that acylated ghrelin was not suppressed during glucose overload in the pregnancy with or without gestational diabetes nor in pregnant women matched by BMI. Nevertheless, acylated ghrelin showed lower values at 60 minutes in gestational diabetes when compared with healthy pregnant women; leading to a possibility that acylated ghrelin has a role in the physiopathology of gestational diabetes. High free fat acids levels are described to be involved in the physiopathology of insulin resistance. Free fat acids were described to be elevated at the third trimester of pregnancy. The objective of the second study was to evaluate the plasma free fat acids levels during oral glucose tolerance test (OGTT) in normal pregnancy and in pregnancies complicated by gestational diabetes. A total of 20 pregnant women 14 pregnant with gestational diabetes and 6 healthy pregnant during third trimester underwent an oral glucose tolerance test (100g-3h-OGTT). Blood samples were drawn for the determination of glucose and free fat acids at the 4 times. We showed significant decline in free fat acids values in both groups from fasting to 60 minutes (p < 0.05). The gestational diabetes group showed higher free fat acids values during all curve points, with significant difference by Two Way ANOVA Repeated Measures (p < 0.001). Free fat acids values declines during OGTT in gestational diabetes but they remain at higher values when compared with normal pregnancy. These higher values in gestational diabetes may be explained by the insulin resistant state of gestational diabetes.