Neonatal Diabetes Mellitus - Causes, Symptoms, Diagnosis, and Treatment

Introduction

There is an absence or lack of insulin production in infants with neonatal diabetes mellitus. Glucose or sugar is obtained from the food we eat. A hormone called insulin allows glucose from the blood to enter the body’s cells. Excess glucose is stored as glycogen in the liver and muscle tissues and utilized when in need. Glycogen is broken down into sugar during demand.

What Is Type 1 and Type 2 Diabetes?

The pancreas is located near the stomach, which produces insulin, which regulates the amount of sugar entering the cells. In type 1 diabetes, the cells that produce insulin in the pancreas are destroyed; hence, there is a deficiency or lack of insulin. In type 2 diabetes, the cells do not normally respond to insulin and develop resistance.

What Is the Difference Between Type 1 Diabetes and Neonatal Diabetes Mellitus?

Type 1 diabetes is also called juvenile diabetes and is often confused with neonatal diabetes mellitus. Type 1 diabetes develops in kids more than six months of age, but neonatal diabetes mellitus occurs in infants within six months of age and rarely after that.

Is Neonatal Diabetes Mellitus a Permanent Condition?

Permanent neonatal diabetes mellitus occurs in 50 % of babies and lasts lifelong. In contrast, transient neonatal diabetes mellitus occurs in the remaining 50 % of babies and can disappear after 12 weeks of birth but can reappear later. Fetuses with neonatal diabetes mellitus do not develop normally in the womb and may weigh less than normal when born. This condition is called intrauterine growth restriction.

What Are the Causes of Neonatal Diabetes Mellitus?

• Neonatal diabetes mellitus is caused due to mutations or changes that take place in a single gene. Hence it is referred to as monogenic diabetes. The beta cells of the pancreas produce insulin and contain K-ATP channels. These channels open and close depending on the level of blood glucose. If the blood glucose level is higher, insulin moves out and regulates the blood glucose level in response to the closure of these channels.

• The K-ATP channel (the channels that sense the metabolic changes in the pancreatic beta cells) consists of 8 subunits. The instruction for forming these subunits is derived from two genes, KCNJ11 and ABCC8. Four subunits are formed from the KCNJ11 gene, and the other four are from the ABCC8 gene. Mutations in these genes can block the K-ATP channel, affecting the release of insulin into the blood and causing neonatal diabetes mellitus.

• The INS gene provides instructions to make insulin. Mutations or changes to this gene can also cause neonatal diabetes mellitus.

• KCNJ11 and ABCC8 mutations are common in permanent neonatal diabetes mellitus. In transient neonatal diabetes mellitus, there is hyperactivity of certain genes present along the long arm of the chromosome (q) called 6q24. Both the affected genes inherited from the parents are active in most cases, but in some cases, only the copy of the gene inherited from either the father or the mother is active. This is referred to as genomic printing. If the copy of each gene inherited from the mother is inactivated, the process is called methylation.

How Is Neonatal Diabetes Mellitus Inherited?

Mostly, neonatal diabetes mellitus is inherited in an autosomal dominant pattern, which means that if one parent has the affected gene, then there is a 50 % chance of the child acquiring the condition. In an autosomal recessive pattern, the affected gene must be inherited from both parents. The child in this condition will have a 25 % chance of acquiring the condition. Neonatal diabetes mellitus can also occur in children without any family history due to new gene mutations.

What Are the Symptoms of Neonatal Diabetes Mellitus?

The symptoms in these infants are as follows:

• Increased appetite.

• Dehydration.

• Frequent urination.

• Increased thirst.

• Rapid breathing.

• Less weight when born.

How Can Neonatal Diabetes Mellitus Be Diagnosed?

Increased blood glucose levels in the infant’s blood or urine can indicate neonatal diabetes mellitus. If this condition occurs in infants younger than six months, then genomic testing is required since neonatal diabetes mellitus is caused by gene mutations. Genetic testing is carried out in specialized labs with the help of blood or saliva samples. The DNA is isolated from the sample and examined for mutations in the gene responsible for causing neonatal diabetes mellitus.

Blood and urine tests can detect elevated blood glucose levels, but genetic testing confirms the diagnosis and helps to plan the treatment. If a parent or a family member is suspected of having neonatal diabetes mellitus, then genetic testing before planning for pregnancy is recommended.

What Is the Treatment for Neonatal Diabetes Mellitus?

• Diet: Once the condition is diagnosed, initial treatment involves balancing the carbohydrate and the calorie intake, keeping in mind that excess weight is not gained as it can cause insulin resistance in the future. Since the baby is born underweight, dietary restrictions can cause a nutrient imbalance.

• Insulin: Due to the baby’s weight, insulin must be given in a careful dosage because too little insulin can cause hypoglycemia (decreased blood glucose levels), and increased insulin can cause hyperglycemia (increased blood glucose levels), either of which can cause neurological problems. Recording the blood glucose level accurately using a blood glucose meter or glucose sensor before administering insulin is recommended. Glucose sensors have the advantage because they can be combined with an insulin pump, and the level of blood glucose can be monitored to prevent hypoglycemia. It also reduces the pricks made on the skin.

• Medication: Medication with sulfonylureas has proved to be effective in treating neonatal diabetes mellitus. These inhibit the pancreas’s K-ATP channel and facilitate insulin’s movement into the bloodstream. Sulfonylureas are available as 5 mg tablets but are not licensed for newborns. Glibenclamide is a drug that belongs to the class of sulfonylureas. Parents or nurses use it by crushing the tablet, mixing it with water, and administering it to the infant through a syringe. However, this can cause a change in the dosage. Hence, the European Medicines Agency (EMA) has developed a formulation of Glibenclamide suitable for newborns, infants, and children, called Amglidia.

Infants with transient neonatal diabetes mellitus may require treatment for a short duration but must be observed to check if the condition reappears.

What Are the Risks Associated With Neonatal Diabetes Mellitus?

The risks include the following:

• Insulin deficiency can trigger the production of harmful chemicals called ketones, which can cause a life-threatening condition called diabetic ketoacidosis. It is a condition in which the body breaks down fat rapidly, and the liver transforms the fats into ketones, making the blood acidic.

• A severe form of neonatal diabetes mellitus can cause DEND Syndrome. It is a triad of neurological problems that cause a developmental delay (muscle weakness or learning disabilities), epilepsy (a condition in which brain activity becomes abnormal, causing periods of unusual behaviors, sensations, and loss of consciousness), and neonatal diabetes.

• Weak muscles.

• A large tongue (macroglossia).

Conclusion:

Neonatal diabetes mellitus can neither be prevented nor completely cured but can be managed by physicians through a multidisciplinary approach or a combination of various specialties. A long-term follow-up of these infants may be required. However, appropriate treatment can help with normal growth and development.