Insulin Therapy For Gestational Diabetes

  • Amani Doklaija  MSc Pharmaceutical Science (Clinical Biochemistry and Toxicology), UEL, UK
  • Helen McLachlan MSc Molecular Biology & Pathology of Viruses, Imperial College London

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According to the World Health Organization (WHO), gestational diabetes mellitus (GDM) is a medical term used to describe glucose intolerance or high blood glucose levels (hyperglycemia) during pregnancy. The body's demand for glucose increases during pregnancy to meet the mother's metabolic needs and support foetal development. However, in some cases, hormonal changes can impair insulin signalling (insulin resistance) and glucose uptake, leading to GDM when the body is unable to produce enough insulin to counteract elevated glucose levels.1

GDM is one of the most prevalent pregnancy complications worldwide. The frequency of GDM is highly expected to increase, along with the increasing prevalence of linked type 2 diabetes mellitus and maternal obesity. This rise accounts for 1–36% of affected pregnancies. Thus, GDM treatment, which involves diet restrictions and a pharmacological approach, plays an essential role in reducing the risk of serious consequences to the foetus such as hypoglycemia, excessive birth weight (macrosomia), and the need for caesarean section.

Risk factors for GDM

Five different risk factors that contribute to GDM development in pregnant women were identified, based on personal, family, and current history, relevant medical history, and past pregnancy.2 

The risk factors are the following: 

  • Previous baby weighing 4.5Kg or above (macrosomia)
  • Body mass index (BMI) above 30 Kg/m2
  • Family history of diabetes
  • Previous gestational diabetes
  • Ethnic origin with a high prevalence of diabetes

Screening and diagnosis of GDM

Diagnostic Tests

Although there are variations in the diagnostic criteria worldwide,, the diagnosis of GDM is usually based on aconfirmatory oral glucose tolerance test (OGTT), which is a 75g two-hour test, performed between 24 and 28 weeks gestation.3 

Oral glucose tolerance test (OGTT)

  • The OGTT is performed after a minimum of 8 hours of fasting
  • First, a sample of blood will be drawn by a healthcare professional
  • A liquid containing a specified concentration of glucose is given to the patient to drink
  • Another sample of blood is taken two hours after drinking the glucose, to check how the body is dealing with the glucose
  • The normal result should be equal to or less than 140 mg/dL (7.8 mmol/L)
  • OGTT could be offered earlier than 24 to 28 weeks pregnant according to the pregnant risk factors for developing GDM

Clinical and adverse outcomes of GDM

Clinical outcomes in pregnant women

The recorded adverse outcomes in individuals who are diagnosed with GDM and their infants are of higher rates than those without hyperglycemia.3 

Women with GDM are at higher risk of developing pre-eclampsia, a serious complication characterised by sudden high blood pressure, thus they are more likely to be induced into labour and have a caesarean section. 

Moreover, women with GDM have an increased prospect of giving birth to large babies. This can lead to the incidence of serious adverse outcomes in these women including perineal lacerations, uterine rupture, and shoulder dystocia. Furthermore, GDM can cause metabolic impairments for women in later life.

Adverse health outcomes in babies 

Pregnancy hyperglycemia has significant adverse health outcomes for babies born to mothers with GDM. Babies born large are at higher risk of sustaining birth injury which includes bone fractures, shoulder dystocia, nerve palsies, and others. Moreover, they are more likely to develop obesity, type 2 diabetes, and metabolic syndrome (a cluster of complications in terms of hypertension, obesity, hypertriglyceridemia, and low concentration of high-density lipoprotein (HDL) cholesterol) in the future. Other possible adverse health outcomes are hypertrophic cardiomyopathy, respiratory distress syndrome, hypoglycemia, hyperbilirubinemia, low blood concentrations of calcium and magnesium, and admission to the neonatal nursery. 

Treatment and therapeutic intervention

The role of insulin during pregnancy

During pregnancy, body demands for glucose levels are increased to support foetus development and meet maternal needs. Thus, the body produces more insulin to maintain glucose levels and facilitate glucose uptake by body cells. However, due to the metabolic and hormonal changes that take place during pregnancy, insulin resistance might occur, reducing its sensitivity to the relevant cell receptors and production by the body over time. 

Insulin and other therapeutic options

Medical nutrition therapy and oral anti-diabetic drugs are the usual course of treatment, but there can be failure of the nutritional plan and oral-antidiabetic drugs to achieve the therapeutic glycemic target, and an inability to tolerate the side effects of oral anti-diabetic drugs (for example, gastrointestinal side effects for metformin). 

Therefore, insulin is the optimal choice to replace oral antidiabetic drugs and medical nutritional plans. Insulin acts here through the facilitation of the uptake of glucose from the bloodstream into the body cells to produce energy, overcoming insulin resistance and low insulin production during pregnancy.

There is a group of heterogeneous insulins which are different in their course of action over time. Rapid-acting or short-acting insulin mimics the endogenous insulin in maintaining glycemic targets in the blood following a meal (postprandial) during hyperglycemia, without causing hypoglycemia before meal intake (preprandial). However, intermediate-acting and long-acting insulin are used for longer-term purposes via providing constant small amounts of insulin over a long period of time regardless of food intake, these types of insulin control the output of hepatic glucose and lipolysis. No form of insulin crosses the placenta at normal therapeutic doses. 

Insulin types used during pregnancy

Short-acting insulin

  • Regular human insulin
  • Begins working in 30 to 60 minutes
  • Peaks at 90 to 120 minutes
  • Lasts for five to 12 hours

Rapid-acting insulin

  • Insulin lispro, aspart, and glulisine are commonly used analogues
  • Takes effect within 15 minutes or less
  • Peaks between 30 to 80 minutes
  • Lasts for three to six hours

Intermediate-acting insulin

  • Neutral protamine Hagedorn insulin, also known as isophane insulin
  • This type of insulin is a longer-acting form of regular human insulin
  • It typically has an onset of action of about 60 to 120 minutes 
  • The time to peak action ranges from 4 to 8 hours
  • The maximum duration of action is about 18 hours

Long-acting insulin

  • Insulin detemir
  • It has an onset of action of about 60 to 120 minutes following administration
  • The action lasts for 18 to 20 hours
  • There is no peak of action

Insulin glargine

  • Onset of action occurs approximately 60 to 120 minutes after administration
  • Duration of action lasts for 24 hours
  • Does not exhibit a peak of action

Pre-mixed insulin

  • Comprises a blend of rapid-acting or short-acting insulin with intermediate-acting insulin
  • Exhibits a quicker onset of action
  • Demonstrates subsequent peak and extended duration of action

Other formulations of insulin

Currently, other routes of administration of insulin are invested by pharmaceutical companies which involve oral and inhaled. These routes are expected to be released to the market in the near future, knowing that they are still at the early stage of trial phases. Additionally, newer analogues of ultra-long insulin are also being implemented. 

Insulin regimens

The selected insulin regimen should be optimal, maintain glycemic targets, minimise the risk of hyperglycemia and hypoglycemia, and achieve ideal pregnancy outcomes across 24 hours. Thus, to reach such a suitable therapeutic plan, several points should be followed up in terms of providing adequate levels to cover food intake, reducing blood glucose fluctuations, and having a proper therapeutic strategy for the correction of blood glucose levels when required. Due to the availability of several types of insulin, there are different regimens of insulin being used throughout the 24 hours, either in the form of multiple injections or continuous administration by subcutaneous insulin infusion. 

Insulin can be administered as

  • A once-daily dose (single dose of insulin) of either intermediate or long-acting insulin each day. Knowing that these individuals might take oral anti-diabetic drugs with insulin
  • A twice-daily regimen (basal-plus) by adding one or two doses of rapid-acting insulin onto an intermediate or basal dose
  • A basal-bolus regimen, this regimen is most commonly used in type 1 diabetes individuals, it offers flexibility based on the quantity of carbohydrates contained in the meals. The regimen includes taking a long-acting or intermediate-acting dose followed by separate injections of rapid or short-acting insulin at each meal
  • A continuous subcutaneous (SC) insulin infusion of rapid-acting insulin delivered via an insulin pump in constant amounts. A bolus of insulin can be provided at meal times to keep glycemic levels controlled within the required therapeutic ranges

How insulin intervention works

Insulin is a hormone produced by the beta cells of pancreas, it acts through regulating the uptake of glucose levels in the bloodstream by certain cells. It also inhibits glucose synthesis and release by the liver. Insulin inhibits proteolysis (breakdown of proteins), lipolysis (breakdown of fats), and gluconeogenesis (synthesis of glucose). Moreover, it enhances protein production and conversion of extra glucose into fats. 

Future directions

Further clinical studies and research are needed to develop more effective diagnostic tools that detect GDM earlier, particularly in women at high risk of developing GDM.4


Gestational Diabetes Mellitus (GDM) is a form of glucose intolerance that occurs during pregnancy, characterized by high blood glucose levels. This condition arises due to hormonal changes that impair insulin signaling and glucose uptake. GDM is becoming increasingly common, correlating with the rising rates of type 2 diabetes and maternal obesity, affecting 1–36% of pregnancies. Effective management, including dietary restrictions and pharmacological interventions, is crucial to prevent severe fetal complications such as hypoglycemia, macrosomia, and the necessity for cesarean sections. Screening for GDM typically involves an oral glucose tolerance test (OGTT) conducted between 24 and 28 weeks of gestation. Managing GDM often requires insulin therapy, especially when diet and oral medications fail to maintain blood glucose levels. Research continues to focus on developing better diagnostic tools and treatments to manage and prevent GDM.


  • Brown, Julie, et al. ‘Insulin for the Treatment of Women with Gestational Diabetes’. The Cochrane Database of Systematic Reviews, vol. 2017, no. 11, Nov. 2017, p. CD012037. PubMed Central,
  • Farrar, Diane, et al. ‘Treatments for Gestational Diabetes: A Systematic Review and Meta-Analysis’. BMJ Open, vol. 7, no. 6, June 2017, p. e015557. PubMed Central,
  • Lefkovits, Yael R., et al. ‘Gestational Diabetes’. Medicine, vol. 50, no. 11, Nov. 2022, pp. 733–36. ScienceDirect,
  • Zhang, Mengxing, et al. ‘Current Guidelines on the Management of Gestational Diabetes Mellitus: A Content Analysis and Appraisal’. BMC Pregnancy and Childbirth, vol. 19, June 2019, p. 200. PubMed Central,

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Amani Doklaija

Master of Science, pharmaceutical science route, clinical biochemistry, and toxicology specialism – UEL (University of East London), London, UK

Amani Doklaija holds a Master of Science in Pharmaceutical Science with a specialization in Clinical Biochemistry and Toxicology from the University of East London (UEL), London, UK. She is a registered overseas community and hospital pharmacist with a strong passion for pharmaceutical and biomolecular research and expertise in medical writing.

Amani possesses a solid background in lab-based procedures and is highly motivated and vigilant in completing complex tasks on time. She is skilled in consultative and advisory strategies and has gained a basic foundation in forensic science and toxicology through her master’s studies and online sessions.

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