TYPE 2 DIABETES MELLITUS AND MONOGENIC DIABETES IN CHILDREN
Diabetes mellitus is a common endocrine disorder that can affect both children and adults. While Type 1 diabetes mellitus is typically diagnosed in children, type 2 diabetes mellitus rates are more common in adults, but in recent years, more children are being diagnosed with this type of diabetes because of their diet and lifestyle.
A small subset of this condition, called monogenic diabetes, develops because of the inheritance of specific genes. These are not as common as type 1 and type 2 diabetes mellitus, and will only be discussed briefly.
Type 2 DM
When sugar (called glucose) enters the bloodstream from the food we eat, the body uses the hormone insulin so that various body organs can access and use glucose to produce energy. In children who constantly consume foods high in sugar, the body gradually will be unable to create enough insulin to keep up and facilitate the movement of glucose from the blood to other parts of the body. This is the basic mechanism for the development of type 2 diabetes mellitus, also known as “adult-onset diabetes mellitus” or “non-insulin dependent diabetes mellitus”.
Children with type 2 diabetes mellitus often have a family history of the condition. For every 100,000 children, around 12.5 kids develop this disease. Those with Native American, Hispanic, and African ethnicity are more prone to type 2 diabetes. Most of these kids are obese, with a history of high-calorie food intake, sedentary activities, and low socioeconomic status. Ironically, babies who are born with intrauterine growth restriction (IUGR) or have a low birth weight are more prone to have type 2 diabetes. Other possible risk factors for a child to develop this condition are the following: psychosocial stress, exposure to smoke and pollutants, and lack of sleep.
In some cases, children may have signs and symptoms that show a combination of both type 1 and type 2 diabetes, especially those who present with diabetic ketoacidosis (DKA).
Signs, symptoms, and diagnostic workup
While most kids with type 1 diabetes are diagnosed after an episode of DKA, only 5-10% of children with type 2 diabetes develop this complication. Typically, type 2 diabetes is diagnosed incidentally during routine healthcare visits or while doing laboratory work for a different condition. Signs and symptoms include a feeling of increased thirst or hunger (polydipsia or polyphagia, respectively), a sudden increase in weight gain, feeling easily tired, the development of dark and rough skin at the nape (called acanthosis nigricans), or red or white stretch marks at the abdomen (striae). However, up to 40% of children may not experience any symptoms at all. Laboratory exams can show increased sugar in the urine (glycosuria), an increased amount of urine (polyuria), and increased lipid levels in the blood (hyperlipidemia).
Screening and criteria for type 2 diabetes mellitus
According to the American Diabetes Association, children who are obese or have risk factors for type 2 diabetes should be screened starting at age 10. This includes those who have a body mass index (BMI) of more than the 85th percentile for their age or weight or height. Some risk factors are:
Kids with type 2 diabetes usually have the following laboratory exam results:
- fasting blood sugar level: 126 mg/dl or higher
- blood sugar level: 200 mg/dl or higher, 2 hours after an OGTT test
- random blood sugar level: 200 mg/dl or higher, with excessive intake of water or food, excessive urination, unexplained weight loss
- glycosylated hemoglobin level: 6.5% or higher
Different treatment options are combined when managing type 2 diabetes in children. At the forefront is lifestyle changes, which includes a proper, low-calorie diet, good eating habits, and regular exercise. Nutritional and exercise counseling are highly recommended for children and their families to work together in managing this disease. In particular, children should have moderate to intense exercise for at least one hour per day, and less than two hours per day of sedentary activities with digital screens.
Medications are also important in controlling blood sugar levels. The most commonly used medicines in children are metformin and insulin. Other less-used drugs include sulfonylureas, acarbose, pramlintide, thiazolidinediones, incretin mimetics, and sodium-glucose transport protein inhibitors.
Blood sugar levels should be monitored regularly. This may depend on the healthcare provider on a case-to-case basis, but it is typically done every 3 months, and will determine if any changes should be done with the treatment options being currently given.
Diabetes can develop due to specific genetic disorders affecting pancreatic beta cells, which produce the hormone insulin. This type is quite rare; only 1-4% of children with diabetes specifically have monogenic diabetes. BMI is not affected, as monogenic diabetes occurs regardless of the child’s weight. However, like type 1 and type 2 diabetes, kids with this condition present with increased food and water intake, and elevated blood sugar levels. These patients are commonly diagnosed incidentally or unexpectedly during routine laboratory evaluation or screening.
Maturity-Onset Diabetes in the Young
In Maturity-Onset Diabetes in the Young (MODY), patients are diagnosed before they turn 25 years old and have one or both parents with diabetes mellitus. The suspicion for MODY increases if there is a family history of diabetes in at least 3 consecutive generations. Children with MODY usually have a normal weight or BMI and present with few or no symptoms. Genetic testing and certain biomarkers are checked to confirm the diagnosis and differentiate it from polygenic diabetes (type 1 or type 2 diabetes). MODY is typically treated with medications, based on the clinical assessment of a healthcare provider.
Transient or Permanent Neonatal Diabetes
Neonatal diabetes is a type of monogenic diabetes diagnosed before a child turns 6 months old. Only 1 out of 300,000-400,000 babies end up having this disease. Like MODY, it is due to specific gene mutations and is diagnosed through genetic testing. However, diabetic infants who were born at least 32 weeks gestational age and higher (late preterm to term infants) have a higher chance of monogenic diabetes than those who were born premature. This condition may be transient (the more common type), or permanent. In transient neonatal diabetes, the condition may resolve after one year of age, but may return during adolescence. In permanent neonatal diabetes, the condition is lifelong.
Because other medical conditions can also change an infant’s blood glucose levels, such as intravenous fluids, sepsis and other medications, a careful evaluation is done to rule out these other causes before considering the patient as a case of neonatal diabetes. Laboratory and imaging exams may include checking for sugar, c-peptide, insulin and insulin antibody levels in the blood, urine levels of ketones, and a pancreatic ultrasound, depending on the assessment of the healthcare provider.
Symptoms are difficult to assess in this age group, but most babies present with difficulties in gaining weight. Several children present with ketoacidosis symptoms, similar to type 1 diabetes. Medications are usually given to treat neonatal diabetes, and the most commonly used are insulin or glibenclamide.
Unfortunately, there may be complications from this condition: babies are at risk for developmental delay, low birth weight, weak muscles, epilepsy, development of a large tongue, and ketoacidosis. As of writing, there is no established knowledge on prevention of neonatal diabetes.
There are different types of diabetes mellitus, affecting a wide range of pediatric age groups. Some may be caused by specific genes while others are multifactorial (diet, lifestyle, genetics, and environmental influences). Early diagnosis and treatment should be done to prevent any complications; however, most cases of diabetes end up becoming a lifelong condition that should be monitored and managed closely.
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- Kliegman, R.M. et al. (2020). Section 6 Diabetes Mellitus in Children. Nelson Textbook of Pediatrics 21st edition. Elsevier.
- Xu, H., & Verre, M.C. (2018). Type 2 Diabetes Mellitus in Children. Am Fam Physician. 2018 Nov 1;98(9):590-594.
- Sanyoura, M., Philipson, L.H., & Naylor, R. (2018). Monogenic Diabetes in Children and Adolescents: Recognition and Treatment Options. Curr Diab Rep. 2018 Jun 22; 18(8): 58.
- Rubio-Cabezas, O. et al. (2014). The diagnosis and management of monogenic diabetes in children and adolescents. Pediatric Diabetes 2014: 15(Suppl 20): 47-64.
- Neonatal Diabetes (2019). Diabetes.co.uk. Taken from: https://www.diabetes.co.uk/neonatal-diabetes.html
- Lemelman, M.B., Letourneau, L., & Greeley, S.A.W. (2017). Neonatal Diabetes Mellitus: An Update on Diagnosis and Management. Clin Perinatol. 2018 Mar; 45(1): 41–59.
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