How Human Placental Lactogen Leads to Gestational Diabetes?

How Human Placental Lactogen Leads to Gestational Diabetes

Human placental lactogen is a hormone made by the placenta that causes the metabolic changes typical of pregnancy. 

It is involved in the alterations in insulin sensitivity, glucose availability, and lipid metabolism that occur during pregnancy.

As pregnancy progresses, insulin sensitivity decreases, which is particularly evident in the second and third trimesters. This decrease in pregnancy-associated insulin sensitivity is normal for the body to ensure proper nourishment of the fetus.

Understanding how pregnancy changes insulin sensitivity is important when learning about gestational diabetes , a form of diabetes that develops during pregnancy

But does it cause gestational diabetes?

 

Evidence indicates that it does not. Human chorionic somatomammotropin is only part of what goes into the complex hormonal and metabolic changes of pregnancy, whereas gestational diabetes occurs when pancreatic insulin secretion is inadequate to overcome increasing insulin resistance.

Article Index

 
  • What Is Human Placental Lactogen (hPL)?
  • What Does hPL Do During Pregnancy?
  • Why Does Insulin Resistance Increase During Pregnancy?
  • How Does hPL Affect Insulin Sensitivity?
  • Does hPL Cause Gestational Diabetes?
  • The Role of hPL in Glucose Availability for the Fetus
  • Why Do Some Pregnant Women Develop Gestational Diabetes?
  • hPL and Pancreatic Beta-Cell Compensation
  • Are High hPL Levels a Sign of Gestational Diabetes?
  • When Is Gestational Diabetes Usually Screened?
  • Other Hormones Involved in Pregnancy Insulin Resistance
  • Does hPL Affect Blood Sugar?
  • Can hPL Be Used to Predict Gestational Diabetes?
  • Frequently Asked Questions
  • Bottom Line

What the Evidence Says?

 

Human placental lactogen is one of the placental hormones which are responsible for the metabolic adaptations characteristic of pregnancy. The hormone contributes to pregnancy-associated changes in insulin sensitivity and fuel metabolism, which are not apparently causally linked to increased risk of developing gestational diabetes.

The analysis conducted by the researchers involved 35 studies, which revealed that there was no association between the levels of hPL and gestational diabetes. It is therefore concluded that gestational diabetes is a multifactorial hormone-related syndrome which involves pregnancy-induced insulin resistance and insufficient compensatory mechanisms by the pancreas.

What Is Human Placental Lactogen (hPL)?

 

Human placental lactogen (hPL), also known as human chorionic somatomammotropin (hCS), is a peptide hormone produced by the placenta. During pregnancy, hPL levels generally rise as gestation progresses and are closely related to increasing placental mass, reaching their highest concentrations during late pregnancy.

Its lactogenic and metabolic effects primarily influence maternal physiology and the maternal-fetal environment.

Some of the hPL’s metabolic effects are connected to:

  • alterations in insulin sensitivity
  • fat metabolism
  • glucose availability
  • maternal energy expenditure
  • beta-cell adaptation

The placenta functions as an endocrine organ as well as an interface between the mother and fetus. Placental hormones influence maternal metabolism, insulin sensitivity, nutrient availability, and the way energy is allocated during pregnancy.

This is why hPL is relevant when discussing pregnancy insulin resistance and gestational diabetes.

However, hPL should not be viewed as a single hormone that independently causes GDM.

What Does hCS Do During Pregnancy?

 

One of the essential metabolic roles of pregnancy-associated hormonal changes is to ensure that the fetus receives a constant influx of nutrients.

As pregnancy proceeds, maternal metabolism is characterized by a progressive transformation.

The tissues of the mother become less sensitive to insulin, while fat becomes a more significant source of energy, including fatty acids.

This shift in metabolism might help maintain glucose levels in the mother’s blood.

Placental hormones is one of several placental hormones thought to contribute to this metabolic adaptation by influencing carbohydrate and lipid metabolism, insulin sensitivity, and maternal fuel utilization.

In simplified terms:

Pregnancy → increasing placental and metabolic signals → increasing maternal insulin resistance → greater availability of glucose and other nutrients for placental-fetal transfer.

Under normal circumstances, the mother’s pancreas reacts to this by producing more insulin.

So, the important question isn’t just whether pregnancy causes insulin resistance.

It does.

The more important question is:

Can the pancreas increase insulin production enough to compensate for that resistance?

 

When the answer is no, blood glucose can rise and gestational diabetes may develop.

Why Does Insulin Resistance Increase During Pregnancy?

 

The development of insulin resistance during pregnancy is a normal physiological process.

The 2026 American Diabetes Association Standards of Care state that pregnancy is characterized by progressive insulin resistance during the second and third trimesters due to diabetogenic placental factors.

Pregnancy naturally increases insulin resistance , but gestational diabetes can develop when the pancreas cannot produce enough insulin to compensate.

Meanwhile, the pancreas typically compensates by producing more insulin to help maintain normal blood glucose levels.

This creates a metabolic balancing act:

Increasing insulin resistance + increasing insulin production = normal glucose regulation

But if insulin production cannot keep pace:

Increasing insulin resistance + inadequate insulin compensation = hyperglycemia and possible GDM

Pregnancy-related insulin resistance generally becomes more pronounced as pregnancy progresses, particularly during the second and third trimesters.

It is essential to note that placental lactogen is only part of the story. Other placental, pregnancy-related, and metabolic factors contribute to the alterations in maternal insulin sensitivity.

How Does hPL Affect Insulin Sensitivity?

 

hPL has traditionally been considered one of the hormones that contribute to the insulin-resistant state of pregnancy.

Its metabolic actions are such that they promote a shift in maternal fuel utilization from carbohydrate to fat while maintaining the availability of glucose.

This is sometimes referred to as a glucose-sparing effect.

The basic physiological concept can be summarized as follows:

  • Pregnancy causes an increase in maternal insulin resistance.
  • Maternal tissues are becoming less responsive to insulin.
  • Reduced glucose uptake by some maternal tissues helps increase glucose availability for transfer across the placenta.
  • There is an increase in maternal lipid metabolism.
  • Glucose can be spared for placental transfer and fetal utilization.
  • The pancreas compensates by secreting more insulin.

This is a normal physiological adaptation whereby the beta cells in the pancreas are able to increase their insulin secretion enough to offset the increased resistance to the effects of insulin. In such a case where compensation is not enough, maternal blood glucose can increase leading to gestational diabetes.

Does hPL Cause Gestational Diabetes?

 

Not by itself.

This is one of the most critical nuances to consider when discussing human placental lactogen and gestational diabetes.

hPL may have metabolic effects that could contribute to the insulin-resistant state of pregnancy, but current human data do not support a role for increased placental lactogen per se in the pathogenesis of gestational diabetes.

A systematic review and meta-analysis of 35 studies found no overall relationship between maternal hPL concentrations and gestational diabetes status.

Additionally, the reviewed studies found no significant associations between hCS and maternal measures of glucose or insulin-resistance in pregnancies complicated by GDM.

Therefore, it would be inaccurate to say:

“High hCS causes gestational diabetes.”

A more accurate interpretation of the evidence is:

“This placental hormone is one of the placental hormones that contribute to metabolic adaptation and pregnancy-related insulin resistance. Gestational diabetes develops when maternal insulin secretion fails to compensate for the increased insulin resistance of pregnancy.”

The Role of hPL in Glucose Availability for the Fetus

 

Glucose is the primary energy source for the fetus.

The placenta provides a flow of glucose from the mother’s blood to the fetus and, consequently, pregnancy requires a coordinated physiological process to ensure the fetus has an adequate supply of nutrients.

Maternal insulin resistance can reduce glucose uptake by maternal peripheral tissues, increasing the availability of glucose for transfer across the placenta.

In addition, maternal carbohydrate metabolism begins to rely more heavily on alternative energy sources such as fats.

This helps preserve glucose availability for transfer across the placenta and supports the nutritional needs of the developing fetus.

Placental lactogen is one of the hormones responsible for this change in metabolism.

It is essential to note that the expression “glucose sparing” does not mean that hPL increases blood glucose levels beyond normal limits.

A normal pregnancy requires a complex set of physiological compensatory mechanisms to adapt to increased metabolic demands.

Why Do Some Pregnant Women Develop Gestational Diabetes?

 

Not every pregnant woman develops gestational diabetes, despite the fact that during pregnancy, there is an increase in insulin resistance.

An important difference is whether pancreatic beta cells can increase insulin secretion sufficiently to compensate for the pregnancy-related increase in insulin resistance and maintain normal blood glucose levels.

Several factors can influence the risk of GDM, including:

These factors do not necessarily mean that the person will develop diabetes during pregnancy.

But they can contribute to decreased ability of the body to compensate for the additional metabolic stress that pregnancy imposes.

This is why two people can experience similar pregnancy-associated hormonal fluctuations but have drastically different glucose responses.

Human Chorionic Somatomammotropin and Pancreatic Beta-Cell Compensation

Pancreatic beta-cell compensation is important in determining whether the physiological insulin resistance of pregnancy is adequately controlled or progresses to hyperglycemia.

A key compensatory response is an increase in insulin secretion by pancreatic beta cells, which helps maintain normal blood glucose despite the increased insulin resistance of pregnancy.

Placental lactogens, including hCS, are also involved in the complex hormonal and metabolic adaptations that occur during pregnancy.

This leads to another key difference between gestational diabetes and other forms of the disease:

While contributing to overall insulin resistance, this placental hormone and other placental hormones are part of the complex physiological mechanism by which the body adapts to pregnancy.

In other words, pregnancy-related hormones are not inherently harmful or equivalent to a disease-causing increase in blood glucose.

They are part of the physiological processes that help the body adapt to pregnancy. Gestational diabetes develops when the body’s compensatory response is insufficient to maintain normal glucose regulation, particularly in the face of increasing insulin resistance.

Therefore, it is more accurate to state that GDM represents a combination of pregnancy-associated insulin resistance and decreased pancreatic response, rather than a disease caused by one specific hormone.

Are High hPL Levels a Sign of Gestational Diabetes?

 

Not necessarily. While hPL has been associated with pregnancy-associated insulin resistance, available human studies do not demonstrate that women with gestational diabetes consistently have higher concentrations of hPL than women who do not have GDM.

A systematic review and meta-analysis of 35 studies found no overall relationship between maternal hPL concentrations and gestational diabetes status.

Therefore, hPL is not a diagnostic test for gestational diabetes.

GDM is diagnosed based on glucose tolerance tests, not blood levels of hPL.

When Is Gestational Diabetes Usually Screened?

 

The 2026 ADA Standards of Care recommend screening for gestational diabetes at 24-28 weeks gestation in pregnant people who are not known to have diabetes or high-risk abnormal glucose metabolism at an earlier point in the pregnancy.

Testing earlier in pregnancy may be appropriate in people with risk factors or abnormal glucose metabolism identified early in pregnancy.

Why is the 24-28 period of gestation emphasized?

 

Because pregnancy-related insulin resistance generally increases as pregnancy progresses, particularly during the second and third trimesters.

As pregnancy progresses, increasing insulin resistance places greater demands on pancreatic beta cells. In some individuals, insulin secretion does not increase enough to compensate for this resistance, resulting in elevated blood glucose and gestational diabetes.

The timing of screening is therefore related to the physiological changes of pregnancy—not the levels of hPL.

Other Hormones Involved in Pregnancy Insulin Resistance

 

It would be too simplistic to explain pregnancy-related insulin resistance through hPL or any single placental hormone alone.

hPL is one of several hormones and metabolic signals that influence carbohydrate metabolism, lipid metabolism, and insulin sensitivity during pregnancy.

These include:

  • placental growth hormone,
  • progesterone,
  • estrogen,
  • prolactin,
  • cortisol,
  • inflammatory cytokines,
  • adipokines, and other metabolites.

The placenta acts as an endocrine gland, and the hormones it produces affect various metabolic processes in the mother’s body: carbohydrate and lipid metabolism, food intake, insulin sensitivity, and availability of nutrients. This is why GDM should be considered a complex multifactorial metabolic disorder.

Does hPL Affect Blood Sugar?

 

hPL contributes to metabolic adaptations that can influence maternal insulin sensitivity and glucose availability.

However, that does not mean that hPL directly causes a person to have a high or low blood glucose level.

Blood glucose levels during pregnancy are determined by numerous factors, including:

  • insulin sensitivity
  • pancreatic insulin production
  • diet
  • physical activity
  • metabolic health before pregnancy
  • genetics
  • body composition
  • other reproductive hormones
  • placental function

Therefore, hPL levels should not be used as an isolated indicator to diagnose or predict gestational diabetes.

What Is the Relationship Between hPL and Insulin Resistance?

 

Human placental lactogen is one of the pregnancy hormones that cause insulin sensitivity in mothers. When hPL increases, maternal metabolism shifts towards using more lipids for energy and becomes insulin resistant. However, it should not be considered the primary hormone causing pregnancy-related insulin resistance and gestational diabetes.

 Therefore, it is not the major hormone responsible for gestational diabetes. The data shows that hPL might contribute to insulin resistance, but most mothers can compensate for increased insulin needs during pregnancy. In most cases, gestational diabetes only develops when the beta-cells are unable to produce enough insulin.

Can hPL Be Used to Predict Gestational Diabetes?

 

Currently, hPL is not a standard diagnostic test for predicting or diagnosing gestational diabetes.

Although researchers have investigated hPL and other placental hormones as potential biomarkers, current evidence does not support hPL as a reliable predictor or diagnostic marker for gestational diabetes.

As such, the standard glucose test is the preferred method of diagnosis.

This is an important point of clarification for anyone browsing information on hPL levels and gestational diabetes.

A hormone that has been the subject of medical research may not necessarily be a clinically relevant one to test.

FAQs on  Human Placental Lactogen and Gestational Diabetes

Frequently Asked Questions About hPL and Gestational Diabetes:

 

Does human placental lactogen cause gestational diabetes?

 

No. hPL is one of several placental hormones that might contribute to the insulin resistant state of pregnancy, but gestational diabetes develops when pancreatic insulin secretion is insufficient to compensate for that resistance.

What Are Normal hPL Levels During Pregnancy?

 

Human chorionic somatomammotropin levels normally rise throughout pregnancy, largely reflecting placental growth, and are highest toward the end of pregnancy. However, hPL levels vary with gestational age and laboratory methods, so there is no single normal range that applies to every pregnancy. Importantly, hPL is not routinely measured to diagnose gestational diabetes, and there is no established hPL level used to diagnose GDM

What is the role of human placental lactogen in pregnancy?

 

hPL is a hormone with both lactogenic and metabolic functions. It is secreted by the placenta and plays a role in carbohydrate and lipid metabolism, being part of the metabolic changes that take place during pregnancy.

Does human placental lactogen trigger insulin resistance?

 

hPL is one of the hormones that contribute to pregnancy-related insulin resistance. The increased resistance is a multi-step process driven by several placental hormones.

Why does insulin resistance increase during pregnancy?

 

The progressive increase in maternal insulin resistance is part of the normal metabolic adaptation to pregnancy. It reduces glucose uptake by some maternal tissues and helps preserve glucose availability for transfer across the placenta, while maternal metabolism increasingly uses other fuels such as fatty acids.

The increased production of insulin by the pancreas that usually occurs in response to elevated blood glucose levels is not enough to counter this process in some individuals, leading to gestational diabetes.

Is there a correlation between high hPL levels and gestational diabetes?

 

The current evidence does not show a significant overall association between hPL levels and gestational diabetes. According to the results of a systematic review and meta-analysis, there was no obvious association between HPL levels and gestational diabetes status.

Is an hPL test used to detect gestational diabetes?

 

hPL testing is not utilized in the diagnostic workup of gestational diabetes. Gestational diabetes is diagnosed using established glucose-based testing strategies, including oral glucose tolerance testing (OGTT), rather than hPL measurement.

Why is gestational diabetes screening performed between 24 and 28 weeks?

 

The progressive increase in pregnancy-associated insulin resistance typically peaks around the third trimester. Screening tests for gestational diabetes are usually done between 24 and 28 weeks in order to identify individuals in whom the compensatory increase in insulin secretion fails to meet the increased demands.

Can gestational diabetes develop despite normal hPL levels?

 

GDM can develop independently of placental lactogen levels. Levels of this hormone are typically elevated to varying levels during pregnancy due to its role in promoting metabolic change. Gestational diabetes can occur when the increase in insulin resistance exceeds the compensatory response of increased pancreatic activity.

Is hPL the only cause of increased insulin resistance during pregnancy?

There are numerous hormonal and metabolic changes throughout pregnancy that contribute to increased insulin resistance. While placental lactogen is one contributor to the process, it is only one of several factors.

Does gestational diabetes imply that placenta lactogen levels are too high?

 

Gestational diabetes is a manifestation of the increased insulin resistance typical of pregnancy, which is driven by a combination of metabolic and placental factors. It is not merely a feature of excessive placenta lactogen production.

Bottom Line: What Is the Relationship Between hPL and Gestational Diabetes?

 

Human placental lactogen is an important pregnancy hormone made by the placenta.

It plays a role in metabolic adaptations that occur during pregnancy, such as changes in maternal insulin sensitivity and fuel utilization, which facilitate provision of nutrients to the fetus. 

However, hPL is not the only factor involved, and it would be incorrect to claim that hPL independently causes gestational diabetes.

A more precise description is that pregnancy causes progressive insulin resistance through the combined effects of placental hormones and other metabolic factors. 

Gestational diabetes develops when pancreatic insulin secretion is insufficient to compensate for this increased resistance and maintain normal blood glucose levels.

This is why the relationship can be summarized as:

Pregnancy → progressive insulin resistance → increased demand for insulin → inadequate pancreatic compensation → hyperglycemia → gestational diabetes

hPL is one part of this process—not the entire explanation.

If you are pregnant and have questions or concerns about gestational diabetes, blood glucose levels or hPL consult with your obstetrician, diabetes specialist or another qualified healthcare professional.

References

 

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