Introduction
Pathophysiology means changes in normal body function (physiology and biochemistry) which lead to developing disease. For example, changes in the insulin levels in the blood as it is decreased or their action becomes impaired it will lead to eventually to diabetes mellitus (Al-Noaemi & Shalayel, 2011). The diabetes mellitus is a metabolic disorder of several causes that cause hyperglycaemia with abnormal metabolism of carbohydrate, fat and protein resulting from abnormal levels of insulin in blood, insulin action, or both. A patient who suffers from diabetes mellitus for long time it will show retinopathy that may cause blindness, nephropathy that may progress to renal failure, neuropathy, foot ulcers, amputation and sexual dysfunction also the patient has high risk to develop cardiovascular disease(WHO, 1999). Gestational diabetes mellitus (GDM) is defined as glucose (carbohydrate) intolerance of different degrees during pregnancy. Neglected Hyper-glycaemia during pregnancy is found to be connected with maternal and perinatal adverse outcomes. (Meek, 2015).
History and discovery of Gestational diabetes mellitus
The first case of gestational diabetes mellitus has been discovered by Bennewitz is multigravida (Frequent pregnancies) a woman, aged 22 years old, she shows severe symptoms of hyperglycaemia during pregnancy and stillbirth of macrosomia fetal (giant fetus) in the modern era in 1824 in Berlin. Bennewitz estimated that only by drying urine using boiling(Hadden & Hillebrand, 1989). Symptom of gestational diabetes mellitus will resolve themselves after delivery. Before the discovery of insulin at 1928 there was no treatment appropriate for women suffering from gestational diabetes mellitus that lead to a disaster condition of both pregnant women and baby so, they were undergoing intense attention from obstetricians and diabetologists to minimize the outcome of disease but not completely treated by adjusting maternal glucose metabolism to normal (GDM, Hadden and Mathiesen, 2016). Gestational diabetes appeared as a concept in 1946. By the 1950s the term “gestational diabetes” was first used. In 1964 a proposal made by O’Sullivan and Mahan described the specific criteria to explain the glucose tolerance level in pregnancy to diagnose women at high risk for developing diabetes after delivery, After, they concluded that the degree of glucose intolerance in pregnant women was correlated to developing diabetes after pregnancy (Buchanan, 2016). In 1979 the criteria were modified by the National Diabetes Data Group (NDDG) with Carpenter and Coustan. In 2000, the American Diabetes Association (ADA) recommended to follow the Carpenter and Coustan criteria for diagnosis of GDM. In 2010, based on a study published in 2008, The International Association of the Diabetes and Pregnancy Study Groups proposed new diagnostic criteria for GDM (Cheung, 2011).
Epidemiology
Prevalence of gestational diabetes mellitus varies widely. Depending on the sample studied and the type of diagnostic criteria were used. It is difficult to predict any uniform prevalence levels because of the wide verities in living conditions, socioeconomic levels and dietary habits in general, prevalence is around 2.4 to 21 % of all pregnancies. Studies show that prevalence in the United Kingdom is around 5%, 3-7% while in the United States was found to be and 2-6% (Cheung, 2011). In another study conducted in Toronto, Canada it was found that around 7% of Caucasian women sample had GDM(Naylor ,1996).
Mechanism
At early pregnancy fasting blood glucose start to decrease and continue during gestation. Insulin sensitivity also decline with advancing gestation to reach at late gestation (34–36 weeks). As a result of insulin resistance, the concentrations of fasting insulin increase. The changes in insulin sensitivity and maternal body fat are inversely proportioned (Dahlgren, 2006). In addition, the liver is also targeted by the decrease in insulin action which cause an increase in Hepatic glucose production (Catalano, 1998).
Pathogenesis
After many studies done by Catalano using euglycaemic hyperinsulinemic clamp techniques and glucose infusion, he concluded that women who had insulin resistant 1 before pregnancy developed GDM. The decrease in insulin sensitivity in late gestation is related to the decreased insulin sensitivity that exists prior to pregnancy. Furthermore, he found that defects in insulin secretion during pregnancy is related to the degree of glucose intolerance. In addition, some evidence shows a correlation between β -cell dysfunction and the severity of glucose intolerance during pregnancy.
(Friedman, 2008) suggested a role of inflammatory factors in the pathogenesis after he found an inverse proportion between circulating TNF α, interleukin 6 (IL6) and insulin sensitivity. Others studies showed an elevation of leptin in GDM which is thought to be determined by thepre-gravid maternal weight (Brown ,2012).
GDM is similar to other types of hyper-glycaemia, it is characterized by the insufficient insulin secretion that doesn’t fulfil the insulin demands.
Thus, the main factor of reveling undiagnosed GDM is the physiological occurrence of insulin resistance (Baz, Riveline and Gautier, 2015).
Insulin resistance, β cell dysfunction, and GDM
Most women with GDM have β cell dysfunction that develops in consequences of chronic insulin resistance. Pregnancy usually induces insulin resistance.
pregnant women with GDM have more insulin resistance when compared to normal pregnant women. In the third trimester, Differences in whole-body insulin sensitivity tend to be small, because of the effects of pregnancy itself on insulin resistance. However, specific and direct measures of insulin sensitivity conducted during the third trimester have showed, in women with GDM, overestimated resistance to insulin’s abiity to stimulate glucose utilization and to help suppress both glucose production and fatty acid levels. (Xiang, 2016).
After delivery, several studies share a common finding, that the acquired insulin resistance of pregnancy subside, and women who had GDM end up with higher insulin resistance than normal women(Buchanan, 2016).which indicates that women who develop GDM have had chronic insulin resistance before.
Etiologies of GDM
there is no specific underlying biochemical etiology. Women with GDM tend to be over-Wight, so mechanisms promoting obesity linking obesity to insulin resistance might have a role in developing GDM.
Type 2 diabetes
GDM is most commonly a precursor of T2D.Longitudinal studies for more than 10 years found that around 25% of GDM will develop T2D (Lee, 2007) (Rice, 2012). Like T2D Women with GDM show insulin resistance before and after pregnancy. (Lauenborg, 2009). In addition, other studies found a strong association between glucose levels during oral glucose tolerance tests in pregnant women and the variants of glucokinase (GCK) and TCF7L2 loci (Freathy, 2010).
Monogenic diabetes
Monogenic diabetes is a form of diabetes that could be seen during pregnancy. It has also been seen that the young (MODY)genes which is a variant in maturity onset of diabetes might contribute to GDM. MODY is defined as any of the several hereditary diabetes that occur due to the mutations in an auto-somal dominant gene affecting insulin production.
MODY 2 is one of the forms that seems to be the most commonly connected with GDM. with a prevalence of about 10% of GDM (Shaat, 2016).
Type 1 diabetes
One of the possible etiologies of GDM is Auto-immune diabetes resulted from the destruction of pancreatic β cells. Which causes about 5–10% of diabetes in the general population (Buchanan, 2016). Auto-immune markers of type 1 diabetes are ranged from 0.98 to 14.7% in women with GDM. It might anticipate the development of type 1 diabetes later on in these women (de Leiva, 2007).
Other factors
Race and ethnicity might have some role in the origin of GDM onset. In a study conducted by(Jenum et al., 2011) in south Asia, he found that GDM may also be a result from non-genetic environmental risk factors such as, obesity, high fat diet and old age. In addition, studies show higher rates in Scandinavians counters and the lowest rates in Native Americans.