Pediatric Type 2 Diabetes Mellitus 

In the past, type 2 diabetes mellitus was very rare in pediatric patients. However, coinciding with the increasing prevalence of obesity among American children, the incidence of type 2 diabetes in children and adolescents has markedly increased, to the extent that it now accounts for as many as one third of all new cases of diabetes diagnosed in adolescents. This trend is particularly pronounced in minority racial and ethnic groups. (See Epidemiology.)^[1]

Complications

Although the natural history of type 2 diabetes mellitus in children is not well studied, the experience accumulated over years of treating adults may help to minimize the occurrence of complications in children. (See Prognosis and Clinical.)

Acute complications of type 2 diabetes include hyperglycemia, diabetic ketoacidosis, hyperglycemic-hyperosmolar state,^[2] and hypoglycemia. Complications from insulin resistance include hypertension, dyslipidemia, and polycystic ovarian syndrome (PCOS).^[3]

As many as 4% of patients with type 2 diabetes initially present in a hyperglycemic-hyperosmolar coma, which can lead to cerebral edema and death if not promptly recognized and treated.^[2]

Long-term complications of type 2 diabetes mellitus include the following:

• Nephropathy
• Neuropathy
• Retinopathy
• Coronary artery disease

A retrospective study found that adults diagnosed with type 2 diabetes before age 45 years have a much higher risk of cardiovascular disease relative to age-matched control subjects. The investigators concluded that early onset type 2 diabetes appears to be a more aggressive disease from a cardiovascular standpoint. (See Prognosis, Clinical, and Treatment.)^[4]

In individuals without diabetes, approximately 50% of their total daily insulin is secreted during basal periods to suppress lipolysis, proteolysis, and glycogenolysis. In response to a meal, rapid insulin secretion (also called first-phase insulin secretion) ensues. This secretion facilitates the peripheral use of the prandial nutrient load, suppresses hepatic glucose production, and limits postprandial elevations in glucose levels. The second phase of insulin secretion follows and is sustained until normoglycemia is restored. A simplified scheme for the etiology of type 2 diabetes mellitus is shown in the image below.

Type 2 diabetes spans a continuum from impaired glucose tolerance and impaired fasting glucose to frank diabetes that results from progressive deterioration of insulin secretion and action. Although the first phase of insulin response is markedly reduced early in the course of the disease, ongoing disorganized basal insulin secretion associated with deterioration of peripheral insulin action occurs during the progression from normal to impaired glucose tolerance to frank diabetes.^[5]

In parallel, as a result of decreased insulin sensitivity in the liver, endogenous glucose output increase adds to the already hyperglycemic milieu, worsening peripheral insulin resistance and beta cell function. Failure of the beta cell to keep up with the peripheral insulin resistance is the basis for the progression from impaired glucose tolerance to overt clinical type 2 diabetes. Longitudinal studies have demonstrated that during the transition between normal glucose tolerance to diabetes, 31% of a person's insulin-mediated glucose disposal capacity, as well as 78% of his or her acute insulin response, is lost.

The UK Prospective Diabetes Study found that beta cell function was 50% of normal at the time of diagnosis of type 2 diabetes in adults.^[6] A case study of the progression of diabetes in an adolescent female found an almost 15% decline in beta cell function per year over the 6-year duration of diabetes, with no substantial changes in insulin sensitivity.^[7] Further prospective studies in young persons with type 2 diabetes are needed in order to clarify the mechanism of disease in this population.

Risk factors

The major risk factors for type 2 diabetes in young persons are as follows:^[8]

• Obesity and inactivity, which are important contributors to insulin resistance
• Native American, black, Hispanic, Asian, or Pacific Islander descent
• Family history of type 2 diabetes in first- and second-degree relatives
• Age of 12-16 years, the mean age range of onset of type 2 diabetes in youths - These ages coincide with the relative insulin resistance that occurs during pubertal development
• Low birth weight and high birth weight^[9]
• Maternal gestational diabetes or type 2 diabetes^{[10, 11]}
• Not breastfed during infancy^[12]

Occurrence in the United States

Although type 2 diabetes is widely diagnosed in adults, its frequency has markedly increased in the pediatric age group since the end of the 20th century. Depending on the population studied, type 2 diabetes now represents 8-45% of all new cases of diabetes reported among children and adolescents.^[13] Most pediatric patients with type 2 diabetes belong to minority communities.

The SEARCH for Diabetes in Youth Study (a US multicenter, observational study conducting population-based ascertainment of cases of diabetes mellitus in individuals over age 20 y) found that the incidence of type 2 diabetes was highest among American Indians aged 15-19 years (49.4 cases per 100,000 person-years). Second and third highest incidence belonged to Asian-Pacific Islanders and blacks, aged 15-19 years, with 22.7 cases per 100,000 person-years and 19.4 cases per 100,000 person-years, respectively.^[14]

International occurrence

An increased prevalence of type 2 diabetes has also been recognized in countries other than the United States, including Japan, where the incidence of type 2 diabetes in school children after 1981 was found to be strongly related to an increasing prevalence of obesity.^[15] Studies among the Indian, British, Chinese, Taiwanese, Libyan, Bangladeshi, Australian, and Maori populations also have shown increasing incidence of youth-onset type 2 diabetes.^{[16, 17, 18, 19, 20, 21, 22, 23]}

Race-, sex-, and age-related demographics

Type 2 diabetes primarily affects minority populations.^[14] From 1967-1976 to 1987-1996, the prevalence of type 2 diabetes increased 6-fold in Pima Indian adolescents and appeared for the first time in children and adolescents younger than age 15 years.^[24] Similar increases in prevalence were observed among Japanese, Asian-American, and black children. In several clinics across the United States, pediatric patients with a diagnosis of type 2 diabetes were from minority ethnic groups (black, Asian, and Hispanic groups).

The prevalence of type 2 diabetes in the pediatric population is higher among girls than boys, just as the prevalence is higher among adult females than it is in adult males.^[8]

The mean age range of onset of type 2 diabetes is 12-16 years; this period coincides with puberty, when a physiologic state of insulin resistance develops. In this physiologic state, type 2 diabetes develops only if inadequate beta cell function is associated with other risk factors (eg, obesity).^[25]

After 30 years of postpubertal diabetes, 44.4% of people with type 2 diabetes and 20.2% of people with type 1 diabetes develop diabetic nephropathy. Overall, the incidence of nephropathy has declined among patients with type 1 diabetes since the end of the 20th century; however, it has not for persons with type 2 diabetes.

So far, no population-based follow-up study has been conducted to determine the long-term prognosis of type 2 diabetes among children and adolescents. Mortality rates and standardized mortality ratios in type 2 diabetes are likely higher than those in type 1 diabetes, given that the major cause of death in type 1 diabetes is end-stage renal disease.

Morbidity and mortality

Overall, morbidity and mortality associated with type 2 diabetes are related to short-term and long-term complications. A longitudinal, population-based study conducted from 1965-2002 in the Arizona Pima Indian population found that youth-onset type 2 diabetes is associated with substantially increased incidence of end-stage renal disease and mortality in middle age.^[26]

In a comparative study among Japanese youths with type 1 and type 2 diabetes, the cumulative incidence of nephropathy among patients with type 2 diabetes was higher than it was in those with type 1 diabetes. Nephropathy also appeared earlier in type 2 diabetes than it did in type 1 diabetes.^[27]

The SEARCH for Diabetes in Youth Study found that American youth with type 2 diabetes have a higher prevalence of elevated albumin-to-creatinine ratio (ACR) than do young persons with type 1 diabetes. The study also found that high blood pressure, hyperglycemia, and high triglyceride concentrations are associated with elevated ACR, independent of the type of diabetes.^[28] Albuminuria is a risk factor for renal failure in pediatric type 2 diabetics. Youth with type 2 diabetes are at a fourfold increased risk of renal failure compared to pediatric patients with type 1 diabetes.^[29]

Among the Pima Indians of Arizona, the risk of retinopathy is lower in patients with youth-onset type 2 diabetes than in those with adult-onset diabetes.^[30]

Education is an essential component of the treatment plan in type 2 diabetes; it is a continuing process involving the child, family, and all members of the diabetes team. The following strategies may be used:

• Appropriate teaching of survival skills at diagnosis
• Explanation and discussion about the possible causes of type 2 diabetes
• Discussion about the need for blood glucose monitoring and the importance of compliance with the drug regimen

Practical skills training includes the following:

• Insulin injections (if insulin is part of the treatment plan)
• Blood and/or urine testing for ketone bodies
• Hypoglycemia recognition and treatment
• Emergency telephone contact procedure
• Psychosocial adjustment to the diagnosis
• Importance of regular follow-up
• Basic dietary advice

Diabetes education is an ongoing process and should address the following issues:

• Formal education during clinic visits or during diabetes classes
• Educational holidays and camps
• Support groups
• Complications - Use times of crisis or acute complications as opportunities to reinforce the importance of some aspects of self ̶ diabetes management that may have been neglected

Educate the patient about the potential side effects of oral hypoglycemic agents (eg, the presence of ketonuria or of any condition predisposing to the accumulation of lactate in patients on metformin).

With regard to the patient’s sexual health, provide advice about contraception, genital hygiene, sexually transmitted diseases, and fungal infections. In pregnant patients with type 2 diabetes, emphasize the importance of good glycemic control before and during pregnancy and discuss the effect of maternal diabetes on the fetus.