The article underscores the increasing occurrence of pregnancy-related diabetes, emphasises personalised insulin-based glycemic control and warns against metformin use in gestational diabetes. It also calls for additional research on its safety in the first trimester.

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Diabetes in pregnancy

Diabetes confers significantly greater maternal and fetal risk due to hyperglycemia, but is also related to chronic complications and comorbidities associated with diabetes. Hyperglycemia in the first trimester of pregnancy leads to congenital malformations.

Specific risks associated with diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, pre-term delivery, neonatal hypoglycemia, hyperbilirubinemia, shoulder dystocia and neonatal respiratory distress syndrome.

Diabetes in pregnancy may increase the risk of obesity, hypertension and type 2 diabetes in offspring later in life.

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Glycemic targets in pregnancy

Fasting and postprandial blood glucose monitoring are recommended in both gestational diabetes mellitus and preexisting diabetes in pregnancy to achieve optimal glucose levels.

Glycemic targets are:

• Fasting plasma glucose- <95 mg/dL 
• 1-h postprandial glucose- <140 mg/dL
• 2-h postprandial glucose- <120 mg/dL

HBA1C is slightly lower during pregnancy in people with and without diabetes due to increased red blood cell turnover. HBA1C target in pregnancy is <6% if this can be achieved without significant hypoglycaemia, but the target may be relaxed to <7% if necessary to prevent hypoglycemia.

Recently maintaining blood glucose between 63 mg/dl to 140 mg/dl (time in range) through continuous glucose monitoring (CGM) above 70% in type 1 diabetes in pregnancy and above 90% in GDM, type 2 diabetes in pregnancy is recommended.

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Management of preexisting type 1 diabetes and type 2 diabetes in pregnancy

Insulin should be used to manage type 1 diabetes in pregnancy. Either multiple daily injections (MDI) or insulin pump technology can be used in pregnancy complicated by type 1 diabetes. Insulin is the preferred agent for the management of type 2 diabetes in pregnancy. Metformin can be given in 2nd and 3rd trimesters of pregnancy to reduce maternal weight gain, macrosomia, and insulin dose required.

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Management of gestational diabetes mellitus

1. Lifestyle intervention includes a dietary pattern with a low-carbohydrate diet with regular physical activity is an essential component of the management of gestational diabetes mellitus and may suffice as treatment for many individuals.
2. Insulin is the preferred medication for treating hyperglycemia in gestational diabetes mellitus if lifestyle intervention fails.
3. Metformin and glyburide should not be used as first-line agents, as both cross the placenta to the fetus and data on long-term safety for offspring are lacking.
4. Other oral and noninsulin injectable glucose-lowering medications lack long-term safety data.
5. Metformin, when used to treat polycystic ovary syndrome (PCOD) and induce ovulation, should be discontinued by the end of the first trimester.

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Metformin vs. insulin in pregnancy

Metformin in gestational diabetes

1. The Offspring Follow-Up (MiG TOFU) study found offspring exposed to metformin for the treatment of GDM in the Auckland cohort were heavier and had a higher waist-to-height ratio and waist circumference than those exposed to insulin in later life.
2. A meta-analysis concluded that metformin exposure resulted in smaller neonates with an acceleration of postnatal growth, resulting in higher BMI in childhood.
3. Due to the potential for growth restriction or acidosis in the setting of placental insufficiency, metformin should not be used in pregnant people with gestational hypertension or preeclampsia or those at risk for intrauterine growth restriction (IUGR).
4. Long-term data is needed for the usage of metformin in the first trimester of pregnancy and some RCTs say metformin can be used safely in the first trimester of pregnancy with caution.

Insulin in gestational diabetes

1. In GDM some patients requiring medical therapy may not be able to use insulin safely or effectively during pregnancy due to cost, language barriers, comprehension, injection phobia or cultural influences. Metformin may be an alternative for these individuals after discussing the known risks and the need for more long-term safety data in offspring.
2. None of the currently available human insulin preparations have been demonstrated to cross the placenta. Regular insulin, aspart, and lispro were approved short-acting insulins in pregnancy. NPH and Levemir were approved for intermediate and long-acting insulins in pregnancy.
3. Optimal glycaemic targets are often easier to achieve during pregnancy with type 2 diabetes than with type 1 diabetes but can require much higher doses of insulin due to insulin resistance.
4. An RCT of metformin added to insulin for the treatment of type 2 diabetes found less maternal weight gain, macrosomia, and fewer caesarean births but there was a doubling of small-for-gestational-age neonates.
5. The addition of metformin to insulin reduces the dose of insulin required in GDM and type 2 diabetes.

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Postpartum care

1. Insulin resistance decreases dramatically immediately postpartum and insulin dose to be adjusted roughly half the pre-pregnancy requirements for the initial few days postpartum.
2. Screen individuals with a recent history of gestational diabetes mellitus at 4–12 weeks postpartum using the 75-g oral glucose tolerance test(OGTT) and clinically appropriate nonpregnancy diagnostic criteria.
3. Individuals with a history of gestational diabetes mellitus should have lifelong screening for the development of type 2 diabetes or prediabetes every 1–3 years.

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Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Ganesh Patti, MD, DM endocrinology, thyroid endocrine centre, Khammam.