Treating Gestational Diabetes with Insulin

Gestational diabetes mellitus (GDM) is a disorder in which a hormone produced by the placenta hinders the body from adequately utilizing insulin.

Instead of being absorbed by the cells, glucose accumulates in circulation. In contrast to type 1 diabetes, gestational diabetes is caused by additional hormones released during pregnancy that might make insulin less efficient, a condition known as insulin resistance.

Following delivery, gestational diabetes symptoms usually disappear, although women with GDM are at an increased risk of developing Type 2 Diabetes.

Gestational diabetes affects between 3 to 8% of all pregnant women in the United States [Ref].

Treating Gestational Diabetes with Insulin:

The primary antihyperglycemic drug prescribed for the treatment of GDM is insulin. However, none of the insulin formulations that are currently on the market has been shown to cross the placenta.

Insulin therapy should be started if glycemic control is not obtained after 1-2 weeks of lifestyle changes.

As advised by numerous guidelines, insulin continues to be the go-to treatment for GDM patients who are unable to achieve glycemic objectives with lifestyle changes. The use of insulin lowers maternal and fetal morbidity [Ref].

Types of Insulin for GDM:

Following are the types of insulin used to control blood sugar levels during pregnancy [Ref].

Human insulin

• Regular Insulin

Regular insulin (U-100, U-500) is used at mealtimes to treat postprandial hyperglycemia and is equivalent to human insulin.

It takes roughly 30 minutes (10–75 minutes) to start working, 3 hours (2.5–5 hours) to reach its peak, and 8 hours to wear off (up to 24 hours for U500).

• Human Insulin Inhalation (Nasal Insulin)

Human inhalational insulin (nasal insulin) is unit-for-unit equivalent to insulin Lispro. It has a 15-minute onset and a 50-minute peak activity period.

The action lasts roughly 2 hours. Human insulin inhalation comes with a boxed warning for bronchospasms in people with chronic lung disease.

Rapid-acting Insulin analog

• Insulin Aspart (Novorapid):

Insulin Aspart, derived from the yeast Saccharomyces cerevisiae, is another human insulin analog. Aspart should be taken 5-10 minutes before eating.

It can be utilized in insulin pumps or for numerous subcutaneous injections. It has a peak action time of 40-50 minutes and an action duration of 3-5 hours.

Insulin Aspart has a lower rate of hypoglycemia than normal insulin. The FDA pregnancy category is B, meaning it is safe to take throughout pregnancy.

Data from two clinical trials (349 exposed pregnancies) show that compared to human insulin, there is no harmful effect on pregnancy or fetal/neonatal health.

• Insulin glulisine (Apidra)

Recombinant insulin is known as insulin glulisine. Escherichia coli is used to produce it. It works quickly—roughly in 10 to 15 minutes. Its complete duration is 4-5 hours, and its peak installs happen in 55 minutes.

Although certain insulin pumps can use it, not all brands of pumps have given their approval. It is classified as Pregnancy Class C by the FDA.

Pregnant patients should be prescribed glulisine with caution in this instance, and the medication should only be taken if the possible benefit outweighs the potential risk to the fetus.

Less than 300 pregnancies have resulted in data from the usage of insulin glulisine in pregnant women.

• Insulin lispro (Humalog):

An analog of insulin called insulin Lispro (U-100 and U-200) is made in Escherichia coli cultures. It starts working after 10 to 15 minutes.

The action lasts 3–4 hours, with the peak occurring between 30 and 90 minutes. It can also be utilized in insulin pens or pumps.

The bioequivalence and pharmacokinetics of the U-100 and U-200 formulations are identical.

Pregnancy is permitted for products in the FDA pregnancy category B. There is no evidence of a negative impact on pregnancy or fetal/newborn health, according to data from numerous exposed pregnancies.

Intermediate-acting Insulin

• Insulin isophane

The intermediate-acting insulin isophane (NPH). Escherichia coli is used to manufacture it as well. It comes in a liquid solution and is comparable to human insulin.

It starts working at most 2 hours after application and peaks at an average of 4 hours. The complete activity time of NPH is 10 to 20 hours.

No limitations on use during pregnancy or gestational diabetes; do not cross the placental barrier. Pregnancy Category B according to FDA.

Basal Insulin analogs

• Insulin detemir

Saccharomyces cerevisiae produces the long-acting analog insulin detemir (U-100). Detemir insulin can take up to two hours to start working, has no clear peak, and can last up to 24 hours.

When compared to the NPH regimen, the detemir insulin has a lower incidence of hypoglycemia in pregnant women.

FDA pregnancy category B; taken into account during pregnancy. It is necessary to weigh the potential benefit against the potentially elevated risk of unfavorable pregnancy outcomes.

An additional 250 outcomes from pregnant women exposed to insulin detemir reveal no evidence of maternal or fetal/neonatal toxicity, whereas data from one clinical trial suggest a probable increased risk of very unfavorable maternal outcomes compared with isophane insulin.

• Insulin Glargine (Lantus):

Insulin Glargine is FDA pregnancy category B. It has a longer half-life compared to Insulin detemir. It is administered as a once-daily injection usually after dinner.

After injecting Insulin Glargine, the blood glucose lowering effect can be observed in about 3 to 4 hours. Its effects last for about 24 hours.

Because of its peak-less effect, it is less likely associated with hypoglycemia, especially nocturnal hypoglycemia.

Insulin glargine does not cross the placental barrier [Ref] and hence does not affect the fetus when it is administered at the usual dosage and the maternal blood sugars are maintained above 70 mg/dl.

• Insulin Degludec (Tresiba):

Insulin Degludec (Tresiba) is ultra-long-acting insulin that has been categorized as pregnancy risk category C.

Its effects can be observed one hour after injecting it and peaks at about 9 hours. The duration of action of insulin glargine exceeds 25 hours and may last for up to 42 hours.

Compared to Insulin detemir and insulin glargine, it is least likely to be associated with nocturnal hypoglycemia.

In one study, it was recommended by the authors that women already on Insulin Degludec can continue it during pregnancy as the pregnancy outcomes were similar to Insulin Glargine and Detemir [Ref].

Insulin Combination Regimens:

Although many other insulin regimens have been suggested to treat hyperglycemia, multiple daily injections (MDI) are by far the most effective and adaptable.

The blood glucose profile should be used to determine the insulin regimen. Therefore, basal insulin should be started if fasting glycemia is greater than 90–95 mg/dl.

It might be neutral protamine Hagedorn or a long-acting insulin mimic. You can determine the basal insulin dosage using your weight: 0.2 units/kg/day.

Rapid-acting insulin or normal insulin should be started before the meal if hyperglycemia occurs after eating (begin with 1 u of insulin for 10–15 g of carbohydrates).

Sometimes postprandial and fasting blood sugar levels are both high, necessitating MDI: 3 mealtime insulin and basal insulin.

The total daily demand for insulin is:

• 0.7 units/kg/day during the first trimester,
• 0.8 units/kg/day during the second trimester, and
• 0.9–1.0 units/kg/day during the third trimester [ref]. This may not apply to every pregnancy.

The total insulin dose in pregestational diabetes is typically up to twice as high as in gestational diabetes.

To combat the combined IR of pregnancy and obesity in cases of morbid obesity, starting insulin dosages might be increased to 1.5–2.0 units/kg. Insulin doses must be continuously optimized, so self-monitoring blood glucose is critical.

In pregnancy, rapid-acting insulin analogs are preferred over regular insulin because they reduce the risk of hypoglycemia and provide better postprandial blood glucose control.