Journal of Diabetes & Clinical Practice
Open Access

GDM (gestational diabetes mellitus) is characterized as glucose intolerance that develops or becomes apparent during pregnancy. As a result, GDM is a result of standard glucose tolerance testing, which is currently done in otherwise healthy people. GDM, like other types of hyperglycemia, is characterised by inadequate pancreatic β -cell activity to supply the body's insulin demands. According to the data, β -cell abnormalities in GDM are caused by the same range of factors that cause hyperglycemia in general, such as autoimmune illness, monogenic reasons, and insulin resistance. As a result, GDM frequently depicts diabetes as it evolves, and as such, it has a lot of potential as a model for studying diabetes etiology and developing and testing diabetes preventive measures.

In various nations, clinical detection of GDM is done in different methods. In general, one or more of the following methods are used in the approaches: Clinical risk assessment, glucose tolerance screening, and formal glucose tolerance testing are the three steps in the process. The procedures are used on pregnant women who haven't been diagnosed with diabetes. The debate over the best approaches for detecting GDM is outside the scope of this paper [1]. The important aspect is that GDM screening is the only mainstream medical technique that tests for glucose intolerance in otherwise healthy people. Regardless of the glucose criteria used to diagnosis GDM, the patients are often young women whose glucose levels during pregnancy are at the upper end of the population distribution. Outside of pregnancy, a tiny percentage of those women had glucose levels that would indicate diabetes.

Glucose regulation

Pregnancy is usually accompanied by increasing insulin resistance that begins around the middle of the pregnancy and develops during the third trimester to levels that are similar to type 2 diabetes insulin resistance. Increased maternal adiposity and the insulin-desensitizing effects of hormones produced by the placenta may cause insulin resistance during pregnancy. The rapid reduction in insulin resistance after birth shows that placental hormones play a significant role.

Studies show potential factors behind normal insulin resistance during pregnancy elsewhere in this supplement. To compensate for the insulin resistance that occurs during pregnancy, pancreatic -cells generally increase their insulin output. As a result, changes in circulating glucose levels during pregnancy are minor compared to the significant changes in insulin sensitivity. Normal glucose control throughout pregnancy is characterised by substantial adaptability of β -cell activity in the face of growing insulin resistance [2].

A restriction in pancreatic β -cell reserve, which manifests as hyperglycemia only when insulin production does not rise to match the increasing insulin requirements of late pregnancy, is one possible aetiology for GDM. Studies undertaken outside of pregnancy appear to corroborate that situation at first look. Insulin levels are generally identical in women without and with a history of GDM, suggesting that the GDM group's insufficient insulin production was restricted to pregnancy. Women with a history of GDM, on the other hand, are often more insulin resistant than non-pregnant women. If the previous GDM patients' β -cell function was normal, insulin levels would be greater. In women with past GDM, the closeness of insulin levels despite varying insulin resistance shows a β-cell malfunction on a qualitative level. Using the hyperbolic connection that exists between insulin sensitivity and insulin secretion, the defect may be measured by expressing insulin levels according to each individual's degree of insulin resistance. This method demonstrates a significant impairment in pancreatic β-cell function both during and after pregnancy in women with GDM.

Gdm in the Context of Chronic Insulin Resistance

Insulin sensitivity is poor in both normal and GDM women during pregnancy, when GDM is diagnosed. Nonetheless, rigorous tests of insulin sensitivity taken in the third trimester found that women with GDM have somewhat higher insulin resistance than normal pregnant women. Insulin's efforts to increase glucose disappearance and reduce both glucose synthesis and fatty acid levels cause further resistance. After birth, normal women have a larger rise in insulin sensitivity than women with GDM because the physiological insulin resistance of pregnancy is reduced. In other words, in women with GDM, the abatement reflects a distinct chronic kind of insulin resistance. This result of higher insulin resistance in women with past GDM has been replicated in investigations that directly assessed whole-body insulin sensitivity.

Given that GDM is a cross-section of glucose intolerance in young women, the mechanisms that contribute to chronic insulin resistance in GDM are likely to be as diverse as those that lead to chronic insulin resistance in the general population. Obesity is a common antecedent of GDM, and modest investigations of women with GDM or a history of it have revealed many of the molecular mediators of insulin resistance that occur in obesity. Increased levels of leptin, as well as the inflammatory markers tumour necrosis factor-α and C-reactive protein, reduced levels of adiponectin, and increased fat in the liver and muscle, are among these mediators.

In vitro studies of adipose tissue and skeletal muscle from women with GDM or a history of the disease revealed abnormalities in the insulin signalling pathway, abnormal subcellular localization of GLUT4 transporters, decreased expression of peroxisome proliferator–activated receptor–γ, and overexpression of membrane glycoprotein 1, all of which could contribute to the observed reductions in insulin-mediated glucose transport [3]. To far, there have been few studies of the cellular mechanisms of insulin resistance in GDM, and it's unclear if any of these abnormalities are universal or even common anomalies underpinning the chronic insulin resistance that is so widespread in GDM.

Autoimmune β-cell Dysfunction and GDM

Antibodies against pancreatic islets (anti-islet cell antibodies) or β -cell antigens like GAD are found in a limited percentage of women with GDM (about 10% in most studies) (anti-GAD antibodies). Although specific physiological investigations on these women are lacking, they are most likely suffering from insufficient insulin secretion as a result of autoimmune injury and loss of pancreatic β -cells. They appear to be developing type 1 diabetes, which is detected by standard glucose test throughout pregnancy. It's unclear if pregnancy can trigger or accelerate islet-directed autoimmunity. Outside of pregnancy, the incidence of anti-islet and anti-GAD antibodies in GDM seems to follow ethnic patterns in the prevalence of type 1 diabetes. Patients with anti-islet or anti-GAD antibodies are frequently, but not always, thin. After pregnancy, they may experience a quick progression to overt diabetes [4].

GDM and Monogenic Diabetes

Variants in autosomes (autosomal dominant inheritance pattern, generally referred to as "maturity-onset diabetes of the young" or "MODY," with genetic subtypes marked MODY1, MODY2, etc.) and mitochondrial DNA can cause monogenic forms of diabetes outside of pregnancy (maternally inherited diabetes, often with distinct clinical syndromes such as deafness). Patients are neither fat or insulin resistant, and the start age is young compared to other kinds of nonimmune diabetes. Both characteristics point to abnormalities in β-cell mass and/or function severe enough to cause hyperglycemia in the absence of insulin resistance. In women with GDM, mutations that induce different subtypes of MODY have been discovered. Mutations in the genes for glucokinase (MODY2), hepatocyte nuclear factor 1 (MODY3), and insulin promoter factor 1 (MODY1) are among them (MODY4). Mitochondrial gene mutations have been discovered in a limited proportion of GDM patients. Only a tiny percentage of GDM cases appear to be caused by these monogenic variants of the disease [5]. They are most likely cases of pre-existing diabetes discovered through standard glucose test during pregnancy.