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Table of Contents
Year : 2021  |  Volume : 18  |  Issue : 3  |  Page : 163-168

Gestational diabetes mellitus: A Narrative Review

Department of Obstetrics and Gynecology, College of Medicine, Al-Mustansiriyah University, Baghdad, Iraq

Date of Submission12-Jan-2021
Date of Acceptance18-Apr-2021
Date of Web Publication29-Sep-2021

Correspondence Address:
Alaa Ibrahim Ali
Department of Obstetrics and Gynecology, College of Medicine, Al-Mustansiriyah University, Baghdad.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/MJBL.MJBL_1_21

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Diabetes mellitus (DM) is a chronic disease that needs medical support and continuing patient education to avoid acute complications and decrease the long-term complications. The prevalence of diabetes is high in many areas, especially Asian. There are many risk factors for developing gestational diabetes, such as advanced gestational age, obesity, family history of DM, and previous delivery of large weight baby. There is higher perinatal morbidity and mortality in untreated cases, but this can be reduced with proper antepartum surveillance and adequate insulin treatment. This article consisted of an acceptable definition, pathogenesis, screening, risk factors, management of diabetes during pregnancy, maternal and fetal complication, and prevention.

Keywords: Diabetes mellitus, fetal surveillance, gestational diabetes, insulin therapy, screening

How to cite this article:
Ali AI, Nori W. Gestational diabetes mellitus: A Narrative Review. Med J Babylon 2021;18:163-8

How to cite this URL:
Ali AI, Nori W. Gestational diabetes mellitus: A Narrative Review. Med J Babylon [serial online] 2021 [cited 2021 Nov 29];18:163-8. Available from: https://www.medjbabylon.org/text.asp?2021/18/3/163/327024

  Introduction Top

Definition of pregestational diabetes mellitus is the occurrence of Type 1 and Type 2 diabetes before pregnancy, whereas gestational diabetes mellitus (GDM) defines as glucose intolerance for the first time during pregnancy.[1],[2] During the last 30 years, the development of the treatment techniques enhances the prevention of diabetic complications during pregnancy, leading to a dramatic improvement in maternal and perinatal outcomes and that’s need clinical efforts to maintain an excellent maternal glycemic control before conception and during pregnancy.[3],[4] There is an increasing prevalence of diabetes mellitus (DM), and its major metabolic disorder caused by the insulin secretion defect or insulin action defect resulting from a defect in insulin secretion, insulin action, or both. As a result, it will lead to chronic hyperglycemia associated with carbohydrates, protein, and fat disturbance.[5],[6]

  Epidemiology Top

Impaired glucose tolerance and impaired fasting glucose play a role in the detection of prediabetes mellitus, which considered as a risk factor for the DM.[7]

The balance between insulin production and insulin sensitivity is responsible for the maintenance of standard glucose tolerance.[8] The ability of insulin to distribute carbohydrates is affected by the secretory response of B-cell of the pancreas; during pregnancy, there will be an adaptation to the alteration in the carbohydrate metabolism; therefore, there is no maternal and fetal effect.[9] Suppose there are any abnormalities in the response of the B-cells, in that case, it leads to an increase in the fetal risk, which occurs when the B-cells output does not meet the increase in the tissue’s insulin demand due to insulin resistance.[10] The pregnancy is a diabetogenic state, the insulin resistance increases in the second trimester due to the release of anti-insulin hormones from the placenta like estrogen, progesterone, cortisol, human placental lactogen, and growth hormone.[11] There will be a glucose intolerance, and postprandial hyperglycemia causes increase in fetal nutrient consumption, leading to normal glucose metabolism with low fasting glucose in pregnant women.[12] The insulin sensitivity reduces about 50%–60% in normal pregnancy when the pancreas’ function is normal; it can compensate for the physiological rise in the insulin resistance during pregnancy.[13] In contrast, in gestational diabetes, the pancreas cannot do this due to the B-cell function deficits[14] in which there is a similarity in the pathophysiology between Type 2 diabetes and gestational diabetes.[15]

  Inflammatory Mediators and their Role in Pregnancy and Diabetes Top

There is an increase in the circulating leukocytes in pregnancy. It regarded as a chronic low-grade inflammatory state triggered by prepregnancy obesity, which can be associated with increases in circulating interlukine-6 and C-reactive protein.[16],[17] These factors can enhance insulin resistance, especially in obese women, and improve substrate availability, resulting in macrosomia development.[18],[19] The most potent predictor in pregnancy for the insulin resistance is the tumor necrosis factor as it may promote insulin resistance by inhibition of insulin signaling through multiple mechanisms.[20],[21]

Pederson hypothesis in 1920; Jorgen Pederson illustrated that maternal hyperglycemia leads to fetal hyperglycemia; therefore, it results in the fetus pancreatic islet cells’ hypertrophy, causing the insulin hypersecretion.[22],[23]

  Screening of Gestational Diabetes Top

Gestational diabetes defined as any level of dysglycemia with onset or first acknowledgement during gestation, so it is essential to do screening for the DM; there are two ways for this screening.[24]

  1. Universal screening: Means screening of all pregnant women[25]

  2. Selective screening: Means screening for high-risk pregnant women when there are risk factors for gestational diabetes such as a family history of Type 2 DM, prior history of gestational diabetes, glycosuria, and impairment in the glucose metabolism.[25]

Screening should start at any time when hyperglycemia signs and symptoms appeared or at 24–28 weeks for all pregnant women.[26],[27]

The oral glucose tolerance test (OGTT) included a 3-h 100 g diagnostic test performed after the 50 g screening test exceeded or met a predetermined blood glucose level.[28]

The diagnoses of gestational diabetes depend on finding of spontaneous blood glucose level >200 mg/dl, fasting plasma glucose >126 mg/dl, or hemoglobin A1c (HbA1c) >6.5% before 20 weeks of gestation.[29] Type 2 diabetes screening indicated at the first prenatal visit for pregnant women with a high risk of gestational diabetes, stillbirth, malformation, frequent mischarge, macrosomia babies, obesity, age >35 year old, symptoms of diabetes, and vascular diseases.[30],[31] The international epidemiological study of 325 pregnant women in nine countries revealed the association between the adverse fetal outcome and glucose intolerance in pregnant with gestational diabetes during the third trimester;[32] they underwent a 75 g OGTT after a period of overnight fasting, measurement of blood glucose level at fasting, 1 h, and 2 h following the glucose intake found increasing in the rate of adverse pregnancy outcome[32],[33] in comparison with the 2 steps approach, there is a higher rate of gestational diabetes diagnosis rather than macrosomia.[34],[35]

There is a controversy about the best screening test for diabetes; several studies found that the one-step method could increase the number of pregnant diagnosed with gestational diabetes depending on one abnormal value.[36],[37] However, there is inadequate data obtained from the randomized control trials for those diagnosed by the one-step approach.[38],[39] A recent study included treating 958 pregnant women with mild GDM regardless of the diagnosis method, whatever treatment there was a similar decrease in cesarean incidence delivery, macrosomia, pregnancy-induced hypertension, and shoulder dystocia.[40] In contrast, other systematic review studies assessed the diagnostic thresholds for gestation diabetes on the fetal and maternal outcome and found that macrosomia was higher in those pregnant diagnosed with two-step approach two-step.[41]

  The Risk Assessment of Gestational Diabetes Top

The patients classified into three groups

Low risk

They do not need routine blood glucose testing if the following are present; no DM history in first degree relatives; there is no abnormal prior obstetric outcome; the age of <25, average weight before pregnancy.[42]

Average risk

Assess the blood glucose at 24–28 weeks by performing one-step method; 100 g diagnostic OGTT for all patients, or by two steps method; glucose challenge test 50 g orally then 100 g diagnostic for patients meeting the threshold.[42]

High risk

If there is one of the following, then perform one of the above-described methods:

Previous history of GDM, Type 2 diabetes, strong family history of diabetes, prior history of glycosuria, and impaired glucose intolerance.[43]

  Complications Top

Fetal complications

Unexplained stillbirth

It is usually associated with poor glycemic control, as hyperglycemia results in a chronic reduction in the level of oxygen; therefore, the fetal metabolites would be responsible for the unexplained stillbirth,[44] which is approved by the low mean umbilical venous pH in those diabetic mothers. Other causes of stillbirth include maternal ketoacidosis, placental insufficiency in overt diabetes with severe preeclampsia, and vascular complication.[45]

Spontaneous abortion

related to poor glycemic control, usually when the HbA1c concentrations are more than 12%.[46]


account 11% in diabetic pregnant the cardiac malformation is the most common anomaly for which the caudal regression associated with diabetes.[46]


incidence is 25%–40%, in diabetic pregnant, and it is an estimated fetal weight >4–4.5 kg or more significant than 90th percentile at any gestational age.[47]

Altered fetal growth

It can be associated with a congenital malformation and advanced vascular complications.[47]

Neonatal complications

preterm birth is one of the severe complications of pregestational diabetes, as well as necrotizing enterocolitis, but the respiratory distress syndrome is mostly associated with gestational diabetes;[48] other complications such as low birth weight, especially those who delivered between 24 and 33 weeks, hypoglycemia of newborn as a result of hyperplasia of B-islet cells due to chronic hyperglycemia in the mother, polycythemia (related to hypoxia as a result of increased fetal oxygen consumption with high fetal erythropoietin), and hyperbilirubinemia.[49]

Maternal complications


There is a higher risk of infection in diabetic pregnancies such as vulvovaginal candidiasis, respiratory, urinary infections, and pelvic sepsis.[50]


Polyhydramnios accounts 3%–30% among diabetic women, it occurs due to fetal glycemic load with polyuria, gastrointestinal obstruction, defect in the fetal swallowing, and high sugar in the amniotic membrane.[51]

Preterm delivery

Preterm delivery accounts for about 605 in diabetic pregnant, it regarded as a severe obstetrical complication.

Acute vascular complications

Acute vascular complications such as acute stroke and coronary artery disease.[52]


is an obstetric complication that leads to preterm delivery in diabetic pregnancies.[52]

Diabetic ketoacidosis

It is a severe medical complication and carries a risk for the fetus for both at time of the event and following it, incidence about 1% in diabetic pregnancies, usually seen among type 1 diabetic women.[52] There are several risk factors which are as follows: infection, noncompliance with insulin, severe hyperemesis gravidarum, B-memetic drugs used as tocolysis and corticosteroids;[53] it occurs as a result of insulin deficiency and increasing the regulatory hormone glucagon, unfortunately, leads to ketone body formation with the gluconeogenesis, and the serum B-hydroxybutyrate used to reflect the level of ketone bodies.[54]

The critical signs and symptoms of diabetic ketoacidosis (DK) are as follows: Abdominal pain, nausea or vomiting, polyuria, and polydipsia, muscular pain, blurred vision, lethargy, drowsiness, altered mental status, tachycardia, tachypnea, coma shock, and fetal distress by abnormal fetal heart.[55]

  Management of Diabetic Ketoacidosis during Pregnancy Top

Investigation revealed the following

glucose hyperglycemia (≥11.0 mmol), positive serum/urine ketones, low serum bicarbonate, the elevated base deficit of ≥4 mEq/l, potassium level may be falsely normal/elevated, multidisciplinary approach should be available.[56]

Intravenous fluid therapy using isotonic saline 0.9% with electrolyte correction, bicarbonate administration if needed, treatment of the predisposing factor, maternal and fetal monitoring.[57]

  Prevention of Diabetic Ketoacidosis in Pregnancy Top

We should outline a strategy for preventing DK from the preconception period until delivery; this can be obtained by pregnancy education, particularly the risk factors, with proper blood sugar control, and decreasing the pregnancy complication.[58]

Chronic complication

Neuropathy and nephropathy accounts for about 10%–50%.[58]


The multidisciplinary team is needed to manage pregnant, seen in a special diabetic clinic with the specialized team included nutritionist, physician, obstetrician, neonatologist, and midwife.[59] The management aims are to optimize the diabetic control depending on the following rules: reasonable glycemic control, proper antepartum surveillance, dietary control, neonatal support, and preconception patient education.[59]

The essential management is glucose control in the first and second trimester to reduce the risks of early pregnancy loss, congenital malformations in infants of diabetic mothers;[60] therefore, the fetal echo at 20–24 weeks advised to exclude structural anomalies, besides the lower serum level of alfa fetoprotein in diabetic pregnant.[61]

The third trimester needs strict glucose monitoring weekly with proper evaluation of preeclampsia, serial ultrasound monthly to detect inadequate fetal growth or excessive growth, fetal surveillance program, umbilical artery Doppler for assessing the uteroplacental circulation to see intrauterine growth retardation, hospitalization for those with uncontrolled glucose level depending on risk factors and the antepartum.[62]

Monitoring of glucose in gestational diabetes mellitus

Four times watching blood glucose level by daily measurement of fasting glucose, 1 or 2 h after each meal, several studies found the better outcome depending on the postprandial glucose control, diabetic pregnancies with reasonable diabetic control depending on the diet need less frequent monitoring.[63]

Hemoglobin A1c concentrations

It should be <6%–6.5% to get lower fetal complications, as it decreases due to rapid red blood cell turnover, so it does not have any benefit during pregnancy.[64]

Nutritional therapy is regarded as the cornerstone in the GDM management, as gestational diabetic women should have the dietary counseling; these are the following dietary approach: Regular small meals consist mainly of slowly absorbed carbohydrate to obtain good glycemic control, maintain the intake of moderate sugar-containing food as it does not relate to excessive weight gain nor hyperglycemia.[65]

In general, the caloric distribution should be 10% at breakfast, 30% at lunch, 30% at dinner, and 30% divided between the snakes, four to five portions of fruits and vegetables every day, eating fish, meat, poultry, milk, oily fish as two portions per day.[65]


it will reduce insulin resistance peripherally, which can assist the dietary therapy for the GDM patients, advised to engage in activity for about 30 min every week.[66]

Medical treatment for the gestational diabetes mellitus

indicated when the fasting glucose >95 mg/dl or postprandial >120 mg/dl for 2 h and >140 mg/dl for 1 h, in general, the oral hypoglycemic drugs not recommended because they can pass through the placental barrier and lead to fetal hypoglycemia.[67] One of the safest oral hypoglycemic medication is the metformin; it causes improvement in the insulin sensitivity, the initial dose is 500 mg given at night for the 1st week then increases to 500 mg two times daily, until 2500–300 mg every day as a maximum dose; the side effects include diarrhea and abdominal pain.[68] Alternative drug for the metformin is the glyburide; it is a sulfonylurea which can promote the insulin secretion, the initial dose is 2.5–2 mg every day in dividing dose, can be given up to 30 mg.[11]

Insulin therapy

starting treatment in GDM when oral hypoglycemic drugs and dietary treatment is inadequate for glycemic control, we use regular and neutral protamine Hagedorn insulin and the short-acting insulin analogue.[69] The treatment depends on the maternal weight and it is illustrated in the [Figure 1] seen above, which revealed the proper insulin doses in the morning and evening, the insulin therapy for the GDM women initiated as an outpatient treatment, and the starting dose is usually lower than the starting dose for the non-GDM diabetic women.[70]
Figure 1: The American diabetes association showing the total insulin dose for the pregnant women

Click here to view

  Conclusion Top

The management of diabetic pregnant is a significant health problem that can burden society. Nonpharmacologic methods such as the diet and exercise could be adequate for many women to get reasonable glycemic control. However, others could not benefit and need additional treatment as pharmacological therapy such as insulin, the first-line treatment then metformin, and glyburide under strict glucose monitoring. It is essential that all pregnant women who have risk factors for diabetes be tested in the first trimester to rule out the presence of overt or preexisting diabetes.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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