Journal of Diabetes & Metabolism

Monogenic Diabetes in Pregnancy: Implications for Maternal and Fetal Health

Sokolayam Ibrahim^{* *}Correspondence: Sokolayam Ibrahim, Department of Cardiology, University of Lagos, Nigeria, Email:

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Introduction

Diabetes during pregnancy can lead to a variety of complications for both mother and child. Monogenic diabetes, caused by mutations in a single gene, accounts for 1-4% of all diabetes cases and is typically misdiagnosed as Type 1 or Type 2 diabetes. In pregnancy, accurate diagnosis is essential because management of monogenic diabetes varies significantly from other types. The two primary forms of monogenic diabetes—Maturity Onset Diabetes of the Young (MODY) and neonatal diabetes—require careful differentiation for optimal maternal and fetal outcomes [1].

Types of monogenic diabetes

Monogenic diabetes during pregnancy usually takes the form of MODY, which is passed down through families in an autosomal dominant manner. Several types of MODY exist based on the gene mutation involved. The most common forms include:

• MODY 1 (HNF4A mutation): This form is associated with increased insulin sensitivity in pregnancy, which can paradoxically lower blood glucose levels and lead to hypoglycemia.
• MODY 2 (GCK mutation): Characterized by mild, stable hyperglycemia that often doesn’t require insulin treatment during pregnancy but must be monitored closely. It usually doesn’t lead to significant pregnancy complications.
• MODY 3 (HNF1A mutation): One of the most common forms of MODY, often requiring insulin treatment during pregnancy due to worsening hyperglycemia, which can increase the risk of fetal macrosomia and neonatal hypoglycemia [2].

Less common forms of neonatal diabetes (caused by mutations such as in the KCNJ11 or ABCC8 genes) can also be present in pregnant women but are extremely rare.

Diagnosis

The diagnosis of monogenic diabetes in pregnancy is critical for choosing the right treatment. Many women with monogenic diabetes are misdiagnosed with gestational or Type 1 diabetes due to the overlap in symptoms. The key indicators of monogenic diabetes include:

• Early-onset diabetes (before age 25), especially in women with a family history of diabetes that spans multiple generations.
• Stable or mildly elevated blood glucose levels that do not fit the typical pattern of gestational diabetes.
• Absence of autoantibodies that are commonly present in Type 1 diabetes.

Genetic testing, often performed through next-generation sequencing panels, is crucial for confirming the diagnosis of monogenic diabetes. This allows for tailored treatment based on the specific gene mutation, which can vary in its effects on insulin production and action.

Impacts on maternal health

Monogenic diabetes poses unique challenges during pregnancy, and the specific risks depend on the type of gene mutation involved. Potential maternal complications include:

• Hypoglycemia: Particularly in women with MODY 1, due to increased insulin sensitivity in pregnancy, leading to frequent hypoglycemic episodes. Careful monitoring of blood glucose levels is required.
• Hyperglycemia and gestational diabetes-like effects: In cases like MODY 3, blood glucose levels may rise significantly as pregnancy progresses, necessitating insulin treatment to avoid complications like preeclampsia, polyhydramnios, and cesarean delivery.
• Mismanagement due to misdiagnosis: Women who are incorrectly diagnosed with Type 1 or gestational diabetes may be overtreated with insulin or not given proper genetic counseling. This can lead to unnecessary complications or ineffective management.

Fetal impacts

The effects of monogenic diabetes on the fetus also depend on the type of monogenic mutation and the degree of maternal hyperglycemia. Key fetal concerns include:

• Fetal macrosomia: Uncontrolled hyperglycemia, especially in MODY 3, can result in large-for-gestational-age infants. This increases the risk of birth injuries, the need for cesarean delivery, and later development of obesity and metabolic disorders.
• Neonatal hypoglycemia: In women with poorly controlled diabetes, infants may experience severe hypoglycemia after birth due to high insulin levels developed in response to maternal hyperglycemia.
• Hereditary diabetes: Depending on the specific gene mutation, there is a 50% chance that the child will inherit the monogenic diabetes gene. Genetic counseling is important for parents, and early screening of the child for diabetes may be necessary.

Management strategies

The management of monogenic diabetes during pregnancy is highly individualized and depends on the type of mutation and clinical presentation. Key components of management include:

• Insulin therapy: Women with MODY 3 or neonatal diabetes mutations may require insulin therapy during pregnancy to control blood glucose levels. However, those with MODY 2 often do not require insulin, and their mild hyperglycemia may be managed through diet and close monitoring.
• Oral hypoglycemic agents: In some forms of MODY, such as MODY 1 and MODY 3, sulfonylureas can be effective in controlling blood glucose without the need for insulin. These agents may be continued in pregnancy after assessing safety.
• Frequent glucose monitoring: Regular monitoring of blood glucose is essential for women with monogenic diabetes to prevent both hyperglycemia and hypoglycemia. Continuous glucose monitors (CGMs) may be useful for real-time adjustments in therapy.
• Multidisciplinary approach: Care should involve a team including endocrinologists, obstetricians specializing in high-risk pregnancies, and genetic counsellors. This ensures optimal management of both the mother's and the baby's health.
• Genetic counselling: Pregnant women with monogenic diabetes should receive genetic counselling to understand the hereditary nature of their condition and the potential implications for their child. Early screening and monitoring of the new-born for signs of diabetes or hypoglycemia are important.

Advances in research

Recent advances in genetic testing have made it easier to diagnose monogenic diabetes in pregnancy. The growing use of next-generation sequencing and the identification of more diabetes-related genes have expanded our understanding of the condition. Moreover, precision medicine approaches are being investigated to tailor treatments to the specific genetic mutations involved. For example, gene therapy and other molecular techniques are being explored as potential future treatments for monogenic diabetes [3].

Discussion

Monogenic diabetes, caused by genetic mutations affecting insulin production, poses unique challenges during pregnancy. Maternal health risks include gestational diabetes, hypertension, and potential complications during labour. For fetal health, there’s an increased risk of congenital anomalies, macrosomia, and neonatal hypoglycemia. Proper management requires a multidisciplinary approach, including genetic counselling, tailored glycemic control, and close monitoring throughout pregnancy. Understanding the implications of monogenic diabetes helps inform clinical strategies to optimize maternal and fetal outcomes, emphasizing the importance of personalized care and early intervention to mitigate risks associated with this condition [4-10].

Conclusion

Monogenic diabetes in pregnant women presents unique challenges that require precise diagnosis and individualized management. Early genetic testing and a multidisciplinary approach are key to improving maternal and fetal outcomes. With advances in genetic research and treatment strategies, the future of managing monogenic diabetes in pregnancy looks promising, offering new opportunities for personalized care.

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