Elsevier

Medical Hypotheses

Volume 104, July 2017, Pages 182-184
Medical Hypotheses

The investigation of the role of proteoglycans and ADAMTS levels in fetal membranes in physiopathological process of gestational diabetes

https://doi.org/10.1016/j.mehy.2014.06.020Get rights and content

Abstract

About 2–5% of all pregnant women develop gestational diabetes mellitus (GDM) during pregnancy and its prevalence has increased markedly within the last decade. GDM is a metabolic syndrome produced by various degrees of carbohydrate intolerance during pregnancy. Various risk factors such as obesity, genetics, environmental factors, and hypertension have been described previously. Maternal and fetal complications occur in around 7% of pregnant women with GDM. In these patients, a relation between proteoglycans and ADAMTS proteases located in extracellular matrix in fetal membranes (placenta, cord, amnion) and complicated pregnancies has already been determined by various animal experiments. Changes in expression, structure and function of ADAMTS proteases and proteoglycans in fetal membranes lead to alteration in the structure of extracellular matrix. If we can establish a balance between these proteoglycans and ADMTS proteases or determine the changes in their structure and functions, it will be possible to predict the risk in high risk pregnancies at early weeks and to initiate treatment early or to follow the target population regularly. In addition, prevention or reduction of maternal and fetal complications may be possible. For this purpose, ADAMTS and proteoglycans the synthesis of which is too much or less, may be targeted and if we would be able to determine and prevent the changes in their levels in the early period of pregnancy, the development of GDM and its complications may be prevented or decreased. Thus, we may identify a marker for early diagnosis and treatment and reduce prematurity, which is the most common cause of fetal death. Fetal and maternal complications, and especially treatment and care costs of prematurity, may also be decreased.

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.

References (14)

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