The investigation of the role of proteoglycans and ADAMTS levels in fetal membranes in physiopathological process of gestational diabetes☆
Introduction
Physiologically, pregnancy is a process associated with insulin resistance and hyperinsulinemia. Gestational diabetes (GDM) is known as carbohydrate intolerance arising at various levels in pregnancy. GDM is one of the most important complications emerging at pregnancy. Hyperglycemia is characterized by various degrees of fetal (macrosomia, intrauterine growth restriction, premature birth, neonatal morbidity, perinatal mortality) and maternal (cesarean section, maternal death, future diabetes) complications. GDM occurs in 7% of all pregnancies [1], [2]. Within the last two decades, the prevalence of gestational diabetes increased by 37% in developing countries and >50% in developed countries [3]. The rate increases further in those who become pregnant at advanced ages, who have family history of diabetes and have GDM in previous pregnancy. The risk of the development of type II DM within 5 years of birth in those with GDM is between 20 and 50% [4], [5].
In pregnancy, insulin resistance becomes pronounced in second trimester, then decreases progressively and returns to normal six weeks after birth. The diagnosis of GDM can be made by either 75 g – 2 h oral glucose tolerance test as recommended by WHO, or 100 g – 3 h glucose tolerance test as suggested by ACOG.
The main event in the pathophysiological process of GDM is the significant decrease in response to insulin and development of insulin resistance. Obesity, genetics and environmental factors may be considered among etiological factors. However, the pathophysiology of this disease still remains to be elucidated, increasing the interest in the etiology of GDM, due to maternal and fetal complications.
Uncontrolled hyperglycemia in young infants, the occurrence of fetal congenital anomalies, intrauterine fetal deaths, severe antenatal and postnatal fetal and maternal complications is quite high in GDM. GDM is diagnosed in the second half of pregnancy, but many complications are related to hyperglycemia in the first half of the pregnancy.
As GDM, is a complex disease, although it is diagnosed in pregnancy, adequate studies have not been carried out in order to prevent physiopathological development. There are many studies investigating obesity at genetic level or environmental factors in order that the development of GDM can be prevented, or diagnosed early and severe maternal and fetal complications associated with hyperglycemia can be decreased. However, definitive etiology and treatment is not addressed in these studies.
Section snippets
Hypothesis
The relation between gestational diabetes and extracellular matrix;
Our hypothesis is based on the fact that GDM appears in pregnancy. It is observed that physiopathological process underlying GDM starts with implantation stage and clinical changes occur in the advanced stages of pregnancy. We suggest that, before the diagnosis of GDM is made, the abnormalities in the levels of ADAMTS and ECM proteoglycans, found in fetal membranes in early stages of pregnancy, modify intrauterine environment
Conclusion
The present study is different from those attempting to explain the pathophysiology of GDM in that it is the first study in which ADAMTS and proteoglycans are investigated together. This hypothesis push forward the idea that a surrogate marker can be determined for the pathophysiology of GDM. Controlled experiments to test this hypothesis may be carried out in mouse models with GDM. In view of the advancing knowledge and techniques, pathophysiological mechanism of GDM was attempted to be
Conflict of interest statement
The authors have no conflict of interest to declare.
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Bone tissue material composition is compromised in premenopausal women with Type 2 diabetes
2020, BoneCitation Excerpt :One of the roles of proteoglycans in bone tissue is to prevent mineralization of the perilacunar matrix around the osteocyte lacunae, and the canaliculi in compact lamellar bone [59], thus the decrease in GAG content in the T2DM patients may signify an alteration in this system, which would be in general agreement with the observations of Mabilleau et al. in a male mouse animal model of T2DM [118]. It is also in agreement with published results showing that proteoglycans are altered (usually decreased) in several tissues (endothelium, vascular wall, kidney, retina, heart, gut epithelial cells, bone and cartilage) with diabetes [119–127]. This decrease associated with hyperglycemic conditions, is reported to be due to a decrease in proteoglycan synthesis or an increase in destruction due to upregulation of enzymes degrading GAGs or destruction by reactive oxygen species [120].
ADAMTS proteases in fertility
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There are no sources of support to declare.