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Management of obese pregnant women with pre-diabetes and type 1 and 2 diabetes mellitus


34.1

Background

Diabetes is the most common metabolic complication of pregnancy and is independently associated with adverse pregnancy outcomes. Some of these adverse outcomes are in common with those occurring in women with obesity alone (e.g. caesarean delivery), while others are unique to diabetes (e.g. ketoacidosis).

Pregestational diabetes (including type 1 and type 2 diabetes) affects approximately 1% pregnancies and is associated with a two to fivefold increased risk of major foetal complications including congenital anomaly (related to early pregnancy hyperglycaemia) and stillbirth. Women with pregestational diabetes are at risk of diabetic ketoacidosis (type 1 > type 2), and have higher rates of caesarean delivery and hypertensive disorders of pregnancy.

Gestational diabetes mellitus (GDM) prevalence is most often reported as 2%–6% pregnancies, but can vary widely depending on the screening approach and population under evaluation. It results in milder degrees of hyperglycaemia compared to pregestational diabetes, but is associated with a 30% increased risk of caesarean delivery, a 50% risk of gestational hypertension, and is a strong risk factor for future type 2 diabetes. Infants of women with GDM are 30% more likely to be large for gestational age, and are at higher risk of childhood obesity.

The majority of women with GDM are obese. However, recent data from the United Kingdom (UK) highlights that 23% women with type 1 diabetes and 65% women with type 2 diabetes also have a body mass index (BMI) ≥30 kg/m 2 based on the first recorded weight in pregnancy. Contemporary, multicentre data from Ireland reveal similar results with 17% women with type 1 diabetes and 52% women with type 2 diabetes having a BMI ≥30 kg/m 2 at the initial antenatal visit.

The large body of research on this topic may be summarised by stating that the impact of maternal obesity and maternal hyperglycaemia on pregnancy outcomes would appear to be independent and additive. This underpins the clinical importance of considering both conditions when treating affected women during pregnancy and postpartum.

Ideally all pregnant women with diabetes will be offered immediate contact and ongoing care in a joint diabetes/antenatal clinic. This clinic should provide access to a multidisciplinary team who can provide expert care tailored to their individual needs.

34.2

Treatment of gestational diabetes mellitus

For all women with GDM, if the fasting plasma glucose concentration is <7 mmol/L at diagnosis, a trial of diet and exercise modification ( Box 34.1 ) with home glucose monitoring ( Table 34.1 ) is recommended.

Box 34.1
Diet and exercise recommendations for women with diabetes and obesity during pregnancy.

  • Dietary reference intake for pregnancy (minimum): 175-g carbohydrate, 71-g protein, 28-g fibre

  • Typical energy requirement: 1800–2500 kCal/day

  • Ideal meal plan: 3 small-to-moderate–sized meals and 3 snacks

  • Positive food choices: whole grains, fresh vegetables, some fruits, low glycaemic index foods. Avoid added sugars and eliminate sugar-sweetened beverages.

  • Moderate exercise (e.g. walking for 30 minutes after a meal) is recommended throughout pregnancy unless there is a specific medical contraindication.

Table 34.1
Approach to antenatal glucose monitoring.
Type of diabetes Daily testing
GDM or Type 2 diabetes controlled with lifestyle +/− oral agents Fasting and 1-hour post meal
GDM or Type 2 diabetes requiring insulin Fasting, premeal, 1-hour post meal and bedtime glucose daily
Type 1 diabetes Fasting, premeal, 1-hour post meal and bedtime glucose daily a

a Continuous glucose monitoring (CGM) should be offered to women with type 1 diabetes as it improves neonatal outcomes. Intermittently scanned CGM may be used if CGM is not possible.

If glucose targets are not met within 1–2 weeks ( Table 34.2 ), treatment should be intensified (necessary in approximately 20% women with GDM).

Table 34.2
Glycaemic goals for women with diabetes during pregnancy.
Timepoint Glucose target (aim for 85% values within goal)
Fasting <5.3 mmol/L
1-hour postprandial <7.8 mmol/L
2-hour postprandial <6.4mmo/L
Women using continuous glucose monitoring Target range is 2.5–7.8 mmol/L. Aim for time in range of >70% and time above range <25%
If taking insulin, glucose should be maintained >4.0 mmol/L at all times. The need to avoid hypoglycaemia may require individualisation of the glycaemic goals.

In the UK, the National Institute for Health and Care Excellence (NICE) recommend metformin as first-line therapy for women with GDM. It is typically introduced at a dose of 500 mg once daily and increased as tolerated to 1000 mg twice daily. Broadly speaking, this is considered a good option for women with obesity as it is weight neutral (see Chapter 4 ).

If this approach does not achieve success within 1–2 weeks, or if the initial fasting plasma glucose is ≥7.0 mmol/L, insulin should be added (with or without metformin) ( Table 34.3 ).

Table 34.3
Insulin therapy during pregnancy.
GDM Type 2 diabetes Type 1 diabetes

  • Aspart and lispro are safe and effective rapid-acting insulin options and are preferable to regular (soluble) insulin.

  • Isophane insulin/neutral protamine Hagedorn (NPH) insulin is considered first choice for basal insulin during pregnancy. Many clinicians use the long-acting insulin analogues detemir or glargine.

  • Insulin should be titrated every 2–3 days depending on glycaemic control. For example, if morning fasting blood glucose is elevated, NPH can be initiated at 0.2 units/kg of body weight. NPH is frequently intensified to a TID regimen, particularly in the presence of premeal hyperglycaemia.

  • Postprandial hyperglycaemia can be managed with premeal rapid-acting insulin analogues (e.g. 1 unit for 10 g carbohydrate).

  • Women established on mixed insulin prior to pregnancy should be transitioned to a multiple daily injection regimen.

  • Women requiring insulin therapy de novo during pregnancy should have therapy introduced in a similar fashion to those with GDM, understanding that treatment will likely start earlier in pregnancy and insulin requirements may be higher.

  • A multiple daily injection regimen or insulin pump therapy is recommended.

  • Aspart and lispro are the rapid-acting insulins of choice.

  • Many clinicians continue the long-acting insulin analogues detemir or glargine, rather than switching to isophane insulin.

  • Insulin pump therapy can be continued during pregnancy. However, hybrid-closed loop functions might need to be deactivated as their fasting goals are typically above that recommended for pregnancy. Initiation of insulin pump therapy during pregnancy should be reserved for those with persistently unstable glucose concentrations or recurrent severe hypoglycaemia.

GDM , Gestational diabetes mellitus.
Note : The results of the EVOLVE ( https://clinicaltrials.gov/ct2/show/NCT01892319 ) and EXPECT ( https://clinicaltrials.gov/ct2/show/NCT03377699 ) studies are expected to be published in the coming months and will provide additional information on basal insulin analogues during pregnancy.

However, the pharmacological approach to GDM is not standardised. For example, the American Diabetes Association recommends insulin as first-line therapy for women with GDM, and either metformin or glyburide/glibenclamide as alternative options. The latter option is a long-acting sulfonylurea, typically initiated at 2.5 mg/day and increased to maximum of 20 mg per day.

The Institute of Medicine guidelines ( Table 34.4 ) on gestational weight gain should be followed. This is especially important for those with both obesity and diabetes, as excessive gestational weight gain will further fuel abnormal foetal growth

Table 34.4
Institute of Medicine guidelines for gestational weight gain.
Pregestational BMI category BMI (kg/m 2 ) Recommended total weight gain (kg) Recommended mean weight gain: trimester 2 and 3 (kg/week)
Underweight <18.5 12.5–18.0 0.51 (0.44–0.58)
Normal weight 18.5–24.9 11.5–16.0 0.42 (0.35–0.50)
Overweight 25.0–29.9 7.0–11.5 0.28 (0.23–0.33)
Obese ≥30.0 5.0–9.0 0.22 (0.17–0.27)
BMI , Body mass index.

Weight loss is not recommended during pregnancy, but increasing physical activity and dietary modifications may be of significant benefit in controlling gestational weight gain and improve the pregnancy outcome.

34.3

Treatment of preexisting diabetes during pregnancy

HbA1c in early pregnancy is a useful marker of pregnancy risk and ideally will be ≤6.5%. While the greatest focus will be on safely reaching the glycaemic goals outlined in Table 34.2 using daily self-monitoring ( Table 34.1 ), further HbA1c testing can be completed in the second and third trimesters of pregnancy to provide further detail on level of risk.

Women with type 2 diabetes previously managed with lifestyle modifications will typically require additional therapy as pregnancy progresses. Consideration should be given to the use of metformin as it reduces excessive maternal weight gain, insulin dosage, and improves glycaemic control in women with type 2 diabetes. However, women should be counselled on the increase in small-for-gestational age infants among those exposed to metformin.

Additional therapeutic options for hyperglycaemia in women with type 2 diabetes during pregnancy include glyburide/glibenclamide and insulin. Insulin therapy should be introduced in a similar fashion to those with GDM ( Table 34.3 ). All alternative glucose-lowering agents are not considered safe in pregnancy.

Treatment of hyperglycaemia in women with type 1 diabetes can be challenging and women need regular review and support to adjust their insulin doses in response to varying degrees of insulin sensitivity and maternal weight gain (see Chapter 4 ). The input of an experienced diabetes educator and dietician can be invaluable. Options for insulin therapy are outlined in Table 34.3 . Women should use either a multiple daily injection regimen or continuous subcutaneous insulin infusion (CSII/insulin pump therapy), with no definitive evidence to recommend one regimen over the other. A systematic review and meta-analysis of 47 studies (predominantly nonrandomised studies), reported that in pregnancies complicated by type 1 diabetes, CSII resulted in better first trimester glycaemic control compared to multiple daily injection insulin therapy, and lower risk of small-for-gestational age; but was associated with higher gestational weight gain and rates of large for gestational age. Additional potential advantages of pump therapy include greater flexibility and a reduction in severe hypoglycaemia.

On the other, continuous glucose monitoring is associated with improvements in maternal glucose and neonatal health outcomes, is cost-effective, and recommended by NICE for all pregnant women with type 1 diabetes.

34.4

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