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Image: “Obesity in children.” by Joe 13. Licence: CC BY-ND 2.0


Overview

Type 2 diabetes mellitus is a condition characterized by various metabolic derangements, such as peripheral insulin resistance and hyperglycemia. It affects multiple system organs, including the cardiovascular system, the cerebrovascular system, the kidneys, liver, and eyes. These complications are responsible for an increase in patient morbidity and mortality.

In the past, type 2 diabetes was known as adult-onset diabetes because its incidence in children was rare. Today, however, type 2 diabetes mellitus is becoming more recognized in children. Increasing incidences are occurring worldwide; each nation has its own demographics on prevalence.

Epidemiology of Type 2 Diabetes Mellitus in Children

Type 2 diabetes mellitus in children has become more common since the last century. Most cases are diagnosed in minority communities. The estimated incidence of type 2 diabetes mellitus in Native American children is around 49 cases per 100,000 persons. The incidence of type 2 diabetes mellitus in other minority groups, such as Asian and African-American children is also high, ranging from 19 to 22.7 cases per 100,000. Up to 45% of newly diagnosed cases of diabetes mellitus in children are attributed to type 2 diabetes mellitus.

Lifetime prevalence in Diabetes Mellitus Type 2 in Children. Image created by Lecturio

Risk Factors

The most critical risk factor for type 2 diabetes mellitus in children is obesity. This finding was confirmed by several local and international studies that were performed in the United States, Japan, Australia, Britain, and India. Pediatric type 2 diabetes mellitus is more common in girls and usually starts at puberty.

It is attributed to the physiological development of a state in which insulin resistance develops; thus, a child with other risk factors has a high chance of inadequate beta-cell function, leading to the development of type 2 diabetes mellitus.

Other risk factors include a family history of type 2 diabetes, high birth weight, maternal gestational diabetes, or maternal type 2 diabetes mellitus, who are not breastfed during infancy. Additionally, conditions with marked insulin resistance, such as polycystic ovarian syndrome, predispose the child to an increased risk of developing type 2 diabetes mellitus. Studies have also shown that antipsychotic drugs increase the chance of individuals developing type 2 diabetes mellitus, with a high significance for children.

Prognosis and Complications of Type 2 Diabetes Mellitus in Children

The exact frequency of long-term complications of type 2 diabetes mellitus in children is unknown. Still, preliminary results show that children are as likely as adults to develop long-term complications of the disease. The long-term complications of type 2 diabetes mellitus in children include nephropathy, neuropathy, retinopathy, and coronary artery disease. These complications are due to microvascular disease and the direct toxic effects of hyperglycemia.

“Hyperglycemia” by Lecturio

Additionally, hypoglycemia due to aggressive diabetic control is associated with cognitive and intellectual deficits in the future and should be avoided. In fact, some studies have claimed that recurrent and severe hypoglycemic episodes in children might be more hazardous to brain development than the natural history of the disease.

Acute complications of type 2 diabetes mellitus are more common in adolescents and teenagers. Diabetic ketoacidosis and hyperglycemic-hyperosmolar states are becoming more commonly recognized in children. Children with type 2 diabetes are also at an increased risk of developing dyslipidemia and hypertension.

Despite recent advances in treatment plans for type 2 diabetes mellitus in adults and children, there is still a risk of nephropathy. Mortality remains higher in children with type 2 diabetes mellitus compared to healthy children or children with type 1 diabetes mellitus.

Etiology and Pathophysiology of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus has a heterogeneous etiology; thus, genetic susceptibility can manifest in social, environmental, and behavioral factors. Patients with type 2 diabetes mellitus have impaired basal insulin secretion, peripheral insulin resistance, and impaired hepatic glucose production.

Type 2 diabetes mellitus occurs when both insulin secretion and insulin inaction are present. Impaired insulin secretion and relative hypoinsulinemia are usually mild at disease onset, but they are clinically relevant since these patients show impaired glucose tolerance but not frank diabetes. Eventually, peripheral insulin action is impaired by insulin resistance, which is also worsened by dyslipidemia. Dyslipidemia is also becoming more severe as the disease progresses, causing a vicious cycle.

The liver is also sensitive to insulin under normal conditions, but this sensitivity is decreased in type 2 diabetes mellitus. This is associated with the liver’s increased glucose production and worsened hyperglycemia. At a certain point, the pancreatic beta-cells can no longer keep up with the demand for insulin due to severe insulin resistance. This insulin resistance, coupled with diminished beta-cell function, leads to frank type 2 diabetes.

The main difference in the pathophysiology of type 2 diabetes between children and adults comes from a recent study that showed up to 15% of female adolescents have no form of insulin resistance. This finding might point towards a different pathology of type 2 diabetes mellitus in children.

Clinical Presentation of Type 2 Diabetes Mellitus in Children

The distinction between type 2 and type 1 diabetes mellitus in children is challenging. Type 2 diabetes mellitus usually has a slow and gradual onset. There is usually a family history of type 2 diabetes. Additionally, children with type 2 diabetes mellitus are more likely to be obese than those with type 1 diabetes mellitus. Asymptomatic children may be checked for hyperglycemia and glycosuria.

The child’s ethnic background may be a significant clue towards the type of diabetes mellitus. African Americans, Asian Americans, and Native Americans are more likely to have type 2 diabetes than the general population. Studies have shown that, generally, children from minority groups have higher insulin levels than same-aged white children. It suggests that race predisposes people to develop diabetes due to higher chances of insulin resistance.

The body mass index in children with type 2 diabetes mellitus is usually above the 85th percentile. Insulin resistance plays a key role in the pathology of type 2 diabetes mellitus, despite some conflicting pathology studies. Acanthosis nigricans is seen in up to 90% of children with type 2 diabetes. The patches are mostly located in intertriginous areas and are easy to identify in obese and darker-skinned people.

Females with type 2 diabetes mellitus, acanthosis nigricans, hirsutism, and menstrual abnormalities should be evaluated for polycystic ovarian syndrome, especially those with chronic anovulation and hyperandrogenism. Hypertension is also commonly seen in children with type 2 diabetes mellitus.

Ophthalmoscopy is indicated in all children newly diagnosed with type 2 diabetes mellitus to establish a baseline and detect early diabetic retinopathy. This is very important since vision loss is the most commonly-feared complication of type 2 diabetes mellitus in children and adults.

Screening for Type 2 Diabetes Mellitus in Children

Children who are overweight, i.e., have a body mass index above the 85th percentile for age and sex, and two of the following characteristics should be screened for type 2 diabetes mellitus:

  1. Having a family history of type 2 diabetes mellitus in a first or second-degree relative.
  2. Belonging to one of the high-risk races or ethnicities mentioned previously.
  3. Having acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovarian syndrome.
  4. Having mild or absent polyuria and glycosuria without ketonuria.
  5. Having insulin resistance disorders.

Screening children who meet the previously-mentioned criteria should commence by the age of 10 years, performed every two years, and be based upon a fasting plasma glucose test.

Diagnostic Workup for Type 2 Diabetes Mellitus in Children

Children with polyuria, polydipsia, or unexplained weight loss, who have a random plasma glucose concentration of 200 mg/dl or more, are diagnosed with diabetes. Additionally, children who undergo a fasting plasma glucose test and have a concentration equal to or higher than 126 mg/dl or a two-hour plasma glucose value greater than or equal 200 mg/dl are also diagnosed with diabetes.

These tests do not help differentiate between type 2 and type 1 diabetes mellitus. Fasting C-peptide and insulin levels are usually increased in type 2 diabetes, but not in type 1 diabetes. Glutamic acid decarboxylase and islet cell antibodies are negative in type 2 diabetes mellitus.

The risk of nephropathy in type 2 diabetes mellitus in children is higher than that associated with type 1 diabetes mellitus; therefore, microalbuminuria should be excluded. Dyslipidemia is also commonly seen in children with type 2 diabetes mellitus and should be excluded.

Treatment of Type 2 Diabetes Mellitus in Children

The goals of type 2 diabetes mellitus treatment in children are to maintain a fasting plasma glucose concentration below 126 mg/dl, resolution of polyuria, nocturia, and polydipsia, maintaining healthy body weight, correcting dyslipidemia, and improving the child’s adaptation to the chronicity of the condition. Improving adaptation is better achieved when the whole family participates in the management plan.

Image: “The pyramid for the five major food groups. The recommended amounts for school-age children are listed in black letters, while our findings for the obese group are written in red and those for the non-obese group in blue characters.” by Garipağaoğlu M, Sahip Y, Budak N, Akdikmen O, Altan T, Baban M – J Clin Res Pediatr Endocrinol (2008). License: CC BY 2.5

The three main aspects of the treatment of type 2 diabetes mellitus are diet, lifestyle modifications, and pharmacotherapy. A healthier diet that is rich in fiber and protein and the incorporation of daily exercise, if possible, is recommended. Metformin should be started as soon as possible. The aim should be to lower HbA1C to a level below 9%.

Statins and angiotensin-converting enzyme inhibitors are indicated in children who do not achieve normotensive blood pressure and who still have elevated LDL and low HDL cholesterol levels despite lifestyle modifications.

Statins, combined with a low intake of fat, and plant sterols consistently reduce LDL-C levels up to 15% are also effective management practices.

Insulin therapy should be initiated if metformin alone was insufficient to correct hyperglycemia in a child with type 2 diabetes mellitus. To consider metformin monotherapy as inefficient, the treatment course should last for at least three months.

Overall, children who develop type 2 diabetes mellitus are at a much higher risk than adults who develop the disease in the long-term. They have increased risks of developing hypertension, dyslipidemia, and cardiovascular disease, as well as stroke.

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