+1 (629)348-3199Commentary - Journal of Diabetology (2022) Volume 6, Issue 1
Glucose regulation and chronic insulin resistance in gestational diabetes mellitus.
Liv Blair*
Department of Medicine, Sao Paulo School of Medicine, Federal University of Sao Paulo, Rua Sena Madureira, São Paulo, Brazil
- *Corresponding Author:
- Liv Blair
Department of Medicine, Sao Paulo School of Medicine
Federal University of Sao Paulo, Rua Sena Madureira
São Paulo, Brazil
E-mail: blairl@uol.com.br
Received: 01-Jan-2022, Manuscript No. AADY-22-104; Editor assigned: 03-Jan-2022, PreQC No. AADY-22-104(PQ); Reviewed: 18-Jan-2022, QC No AADY-22-104; Revised: 21-Jan-2022, Manuscript No. AADY-22-104(R); Published: 28-Jan-2022, DOI:10.35841/aady-6.1.104
Citation: Blair L. Glucose regulation and chronic insulin resistance in gestational diabetes mellitus. J Diabetol. 2022;6(1):104
Introduction
GDM (gestational diabetes mellitus) is defined as glucose intolerance that appears or develops during pregnancy. As a result, GDM is the result of conventional glucose tolerance testing, which is currently performed in otherwise healthy individuals. GDM, like other kinds of hyperglycemia, is marked by insufficient pancreatic-cell activity to meet the body's insulin requirements. According to the findings, -cell abnormalities in GDM are caused by the same variables that cause hyperglycemia in general, including autoimmune disease, monogenic causes, and insulin resistance. As a result, GDM usually reflects diabetes as it progresses, and as a result, it has a lot of promise as a model for researching diabetes aetiology and creating and testing diabetes prevention strategies [1].
Clinical detection of GDM is done in a variety of ways in different countries. In general, the approaches employ one or more of the following methods: The three steps in the approach are clinical risk assessment, glucose tolerance screening, and formal glucose tolerance testing. Pregnant women who haven't been diagnosed with diabetes are subjected to the procedures. This research does not address the issue over the optimum methods for detecting GDM. The fact that GDM screening is the sole mainstream medical tool for testing glucose intolerance in otherwise healthy adults is critical. Regardless of the glucose criterion used to diagnose GDM, the patients are frequently young women with high glucose levels during pregnancy. A small minority of those women had glucose levels that would suggest diabetes outside of pregnancy.
Glucose regulation
Pregnancy is frequently accompanied by an increase in insulin resistance that begins around the middle of the pregnancy and progresses to levels similar to type 2 diabetes insulin resistance by the third trimester. Insulin resistance during pregnancy may be caused by increased maternal adiposity and the insulin-desensitizing effects of hormones generated by the placenta. Placental hormones play a crucial role in the quick reduction of insulin resistance after birth, as seen by the rapid reduction in insulin resistance after birth [2].
In this supplement, studies demonstrate potential explanations for normal insulin resistance during pregnancy. Pancreatic β-cells normally boost their insulin secretion to compensate for the insulin resistance that arises during pregnancy. As a result, changes in circulating glucose levels are small compared to the major changes in insulin sensitivity that occur during pregnancy. In the face of increasing insulin resistance, normal glucose regulation during pregnancy is characterised by high flexibility of -cell activity.
One putative aetiology for GDM is a restriction in pancreatic -cell reserve, which appears as hyperglycemia only when insulin output does not rise to match the growing insulin demand of late pregnancy. At first glance, studies conducted outside of pregnancy appear to support that conclusion. Insulin levels in women without and with a history of GDM are nearly equal, implying that the GDM group's deficient insulin production was limited to pregnancy. Women who have had GDM in the past are more likely to be insulin resistant than non-pregnant women. Insulin levels would be higher if the prior GDM patients' -cell function was normal. The closeness of insulin levels in women with previous GDM, despite varied insulin resistance, indicates a qualitative -cell dysfunction. The deficiency can be assessed by expressing insulin levels according to each individual's degree of insulin resistance, according to the hyperbolic relationship that exists between insulin sensitivity and insulin secretion. This approach indicates that women with GDM have a severe impairment in pancreatic-cell function both during and after pregnancy.
GDM in the context of chronic insulin resistance
During pregnancy, when GDM is diagnosed, both normal and GDM women have impaired insulin sensitivity. Despite this, third-trimester insulin sensitivity tests revealed that women with GDM have slightly higher insulin resistance than normal pregnant women. Insulin's attempts to increase glucose disappearance while lowering glucose synthesis and fatty acid levels result in increased resistance. Because the physiological insulin resistance of pregnancy is lowered, normal women have a greater increase in insulin sensitivity after birth than women with GDM. In other words, the reduction in insulin resistance in women with GDM represents a separate chronic type of insulin resistance. This finding of increased insulin resistance in women with a history of GDM has been confirmed in studies that measured whole-body insulin sensitivity [3].
Given that GDM is a subset of glucose intolerance in young women, the mechanisms underlying chronic insulin resistance in GDM are likely to be as diverse as those behind chronic insulin resistance in the general population. Obesity is a common antecedent of GDM, and small studies of women with GDM or a history of it have revealed many of the molecular mediators of insulin resistance found in obese people. These mediators include increased leptin levels, as well as the inflammatory markers tumour necrosis factor- and C-reactive protein, lower adiponectin levels, and increased fat in the liver and muscle.
In vitro studies of adipose tissue and skeletal muscle from women with GDM or a history of the disease found abnormalities in the insulin signalling pathway, abnormal subcellular localization of GLUT4 transporters, decreased expression of peroxisome proliferator–activated receptor–, and overexpression of membrane glycoprotein 1, all of which could contribute to the observed reductions in insulin-mediated glucose transport. There have been few investigations of the cellular causes of insulin resistance in GDM so far, and it's unclear if any of these abnormalities are universal or even frequent aberrations underlying the chronic insulin resistance seen in GDM.
Autoimmune β-cell dysfunction and GDM
Antibodies against pancreatic islets (anti-islet cell antibodies) or -cell antigens such as GAD are identified in only a small number of women with GDM (approximately 10% in most studies) (anti-GAD antibodies). Despite the lack of precise physiological studies on these individuals, they are most likely suffering from inadequate insulin secretion as a result of autoimmune damage and pancreatic -cell death. They appear to be developing type 1 diabetes, which may be identified during pregnancy with a simple glucose test. It's uncertain if pregnancy may cause or speed up islet-directed autoimmunity. Anti-islet and anti-GAD antibodies in GDM appear to mirror ethnic variations in the frequency of type 1 diabetes outside of pregnancy.
GDM and monogenic diabetes
Variants in autosomes (an autosomal dominant inheritance pattern known as "maturity-onset diabetes of the young" or "MODY," with genetic subtypes labelled MODY1, MODY2, and so on) and mitochondrial DNA can produce monogenic diabetes outside of pregnancy (maternally inherited diabetes, often with distinct clinical syndromes such as deafness). Patients are neither obese or insulin resistant, and the onset age is rather early in comparison to other types of nonimmune diabetes. Both of these traits suggest to -cell mass and/or function problems severe enough to generate hyperglycemia in the absence of insulin resistance. Mutations that cause distinct subtypes of MODY have been detected in women with GDM. Glucokinase (MODY2), hepatocyte nuclear factor 1 (MODY3), and insulin promoter factor 1 (MODY1) genes all have mutations (MODY4). In a small number of GDM patients, mitochondrial gene alterations have been detected. These monogenic GDM variants appear to be responsible for just a small proportion of GDM cases. They're very certainly examples of pre-existing diabetes found during pregnancy using a normal glucose test.
References
- Lapolla A, Dalfrà MG, Fedele D. Diabetes related autoimmunity in gestational diabetes mellitus: is it ¬important? Nutr Metab Cardiovasc Dis. 2009;19(9):674-82.
- Thellin O, Coumans B, Zorzi W, et al. Tolerance to the foeto-placental “graft”: Ten ways to support a child for nine months. Curr Opin Immunol. 2000;12(6):731-37.
- Stowers JM, Sutherland HW, Kerridge DF. Long-range implications for the mother: The Aberdeen experience. Diabetes. 1985;34(2):106-10.
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