Scope and Purpose

This evidence review will be used by the United States Preventive Services Task Force (USPSTF) to make a recommendation on screening asymptomatic children and adolescents for prediabetes and type 2 diabetes. The USPSTF does not have a previous recommendation on this topic for children and adolescents. The USPSTF recommends screening for prediabetes and type 2 diabetes in adults ages 35 to 70 years who are overweight or who have obesity (B recommendation). The USPSTF states that clinicians should offer or refer patients with prediabetes to effective preventive interventions. The USPSTF has I statements for screening for high blood pressure in children and adolescents and for screening for lipid disorders in children and adolescents. The USPSTF recommends that clinicians screen for obesity in children and adolescents age 6 years or older and offer or refer them to comprehensive, intensive behavioral interventions to promote improvements in weight status (B recommendation).

Condition Definition

Diabetes mellitus (DM) refers to a range of metabolic disorders characterized by hyperglycemia. Table 1 shows general categories and definitions of DM used by the American Diabetes Association (ADA).¹ The ADA guidelines emphasize that type 1 and type 2 diabetes are heterogeneous diseases in which clinical presentation and disease progression may vary considerably. Both type 1 and type 2 diabetes may present in children or adults.¹ The focus of this review is on screening for asymptomatic type 2 diabetes, which is characterized by insulin resistance and relative insulin deficiency.

Table 1

Classification of Diabetes (Adapted From ADA Guidelines).

Definitions of prediabetes and diabetes in children and adolescents are the same as in adults. Three tests can be used to identify prediabetes and type 2 diabetes: hemoglobin A1c, fasting plasma glucose, or an oral glucose tolerance test (OGTT) (Table 2). Prediabetes is the term used for individuals whose blood glucose levels are considered higher than normal but do not meet criteria for diabetes. Individuals diagnosed with prediabetes include those who meet criteria for impaired fasting glucose (IFG), meet criteria for impaired glucose tolerance (IGT), and have a glycated hemoglobin (A1c) from 5.7 to 6.4 percent.

Table 2

Criteria for the Diagnosis of Type 2 Diabetes and Prediabetes (Adapted From ADA Guidelines).

Etiology and Natural History

Type 2 diabetes in youth is characterized by insulin resistance combined with relative insulin deficiency.^{2, 3} At diagnosis or in the following years, some youth have lost approximately 80 percent of their pancreatic beta cell function, resulting in an inability to compensate for increased insulin resistance.^3–5 This pancreatic dysfunction does not appear to be mediated by antibodies against the pancreatic islet cells (as occurs in type 1 diabetes).⁶ Although the progression through obesity, insulin resistance, glucose intolerance, and type 2 diabetes is not fully understood in youth, the timing of this progression appears to be shorter and less predictable compared with adults.^{6, 7}

The major acute complications of type 2 diabetes in youth are diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS), which can both result in death if left untreated.⁸ Rates of DKA have been decreasing over time with the most recent estimates from 2008 to 2014 indicating that 6 percent to 11 percent of youths with type 2 diabetes had DKA at presentation.^{6, 9–11} Higher prevalence of DKA has been associated with younger age at diagnosis, minority race/ethnicity, male gender, and lower family income and parental education.^{6, 10} Although less frequent than DKA, the incidence of HHS in youth is increasing.^{12, 13} A 2016 study found HHS in 2 percent of youth at diagnosis of diabetes.⁹ HHS also appears to be more frequent in non-Hispanic black youths and Hispanic youths than in non-Hispanic white youths.⁶

Youth with type 2 diabetes have an increased prevalence of associated chronic comorbidities, including hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Development of type 2 diabetes during childhood or adolescence results in a longer duration of exposure to a dysfunctional metabolic milieu over the lifetime. This may result in an increased risk of chronic microvascular complications including retinopathy, nephropathy, and neuropathy compared with those who develop type 2 diabetes in adulthood. The impacts on macrovascular complications such as cardiovascular and renal disease and long-term mortality have not been well studied in youth. However, in a study of Pima Indian youth, those with onset of type 2 diabetes before 20 years of age had mortality rates at aged 20 to 54 years that were 2.1 times higher than among persons with diabetes onset at or after age 20 years and 3.1 times higher than nondiabetic persons.¹⁴

Relatively few data are available to ascertain the natural history of prediabetes in youth. Placebo arms of randomized, controlled trials (RCTs) have found that anywhere from 22 percent to 52 percent of children and adolescents with prediabetes returned to normal glycemia or normal glucose tolerance without intervention over 6 months to 2 years (Contextual Question [CQ] 1 in Appendix A).

Risk Factors

Obesity and excess adipose tissue (especially when centrally distributed) are the most important risk factors for type 2 diabetes in youth.^15–17 The SEARCH for Diabetes in Youth study (SEARCH) reported that between 2001 and 2004 nearly 80 percent of youth with type 2 diabetes were obese and that an additional 10 percent were overweight.¹⁶ Family history is a strong risk factor, with estimates that 50 to 75 percent of youth with type 2 diabetes have at least one parent with type 2 diabetes and nearly 90 percent may have a positive family history if grandparents are also included.^18–21

The vast majority of pediatric cases occur after age 10, with the peak age for presentation occurring at mid-puberty (approximately age 14 years).^{22, 23} This timing is likely related to the physiologic, but transient, pubertal insulin resistance that can aggravate the preexisting metabolic challenges of obesity.^{17, 24, 25} Some studies indicate that adolescent girls are 1.3 to 1.7 times more likely than boys to be diagnosed with type 2 diabetes, although the reasons are not well understood.^{15, 19, 26, 27} Research suggests that maternal obesity and gestational diabetes contribute to obesity and type 2 diabetes in youth.^{6, 17} For example, in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort, one third of youth with type 2 diabetes had been born after a pregnancy complicated by preexisting diabetes or gestational diabetes mellitus.¹⁷

A review summarizing differences in the frequencies of type 2 diabetes by race, ethnicity, socioeconomic position, area of residence, and environmental toxins noted that the causes of differences (e.g., between different racial and ethnic groups) are not well understood.²⁸ Compared with the type 2 diabetes rate in non-Hispanic white youth, the rate in Native American, African American, and Hispanic youth has been shown to be 8, 5, and 4 times higher, respectively.²⁶ The relative contributions of various factors to racial/ethnic differences are largely unknown.²⁸ As with many other health disparities,^29–31 structural factors that disproportionately affect nonwhite populations (e.g., toxic stress, structural and interpersonal racism, economic inequities) may contribute significantly to differences by race/ethnicity. Other potential contributing factors include metabolic characteristics, cultural/environmental influences, and quality of and access to healthcare.¹⁷

CQ 5 (Appendix A) summarizes risk assessment tools that are feasible for use in primary care settings, accurately predict the risk of prediabetes or type 2 diabetes for children and adolescents, and have been externally validated in U.S. populations. Briefly, two such tools were identified: one using an automated computer system based on ADA guidelines and one that adapted the Tool for Assessing Glucose ImpairmenT (TAG-IT) adult risk assessment tool for pediatrics.

Prevalence and Burden

The 2017–2018 National Health Interview Survey from the Centers for Disease Control and Prevention (CDC) estimated that 210,000 children and adolescents younger than age 20 years (or 2.5 per 1,000 U.S. youths) had been diagnosed with diabetes, of which approximately 23,000 had type 2 diabetes.³²

Most prevalence and incidence data on type 2 diabetes in children come from a limited number of subjects from the SEARCH for Diabetes in Youth Study, a population-based study of children under age 20 years in several geographic regions (county-based from 4 states, insurance-based from 1 state, and from select Native American reservations from 2 additional states) that the CDC and National Institutes of Health have funded since 2000. It found that of 3.5 million children under age 20 years in 2009, 837 (or 0.24 per 1,000) had type 2 diabetes. Based on these data, an estimated 20,262 youth under age 20 years had type 2 diabetes in the United States at that time.³³ This same dataset found that the prevalence of type 2 diabetes was highest in American Indian/American Native (0.63/1,000), black (0.56/1,000), and Hispanic (0.40/1,000) youth and lowest in Asian/Pacific Islander (0.19/1,000) and non-Hispanic white (0.09/1,000) youth.³³ The generalizability of this demographics data is uncertain. It is limited by its small sample size (fewer than 900 people contributing to the data) and selection from particular geographic regions, insurance coverage, and/or specific reservations with low numbers in each.

Data indicate that the prevalence and incidence of type 2 diabetes are rising; in 2001, the overall prevalence of type 2 diabetes in children ages 10 to 19 years was 0.34 per 1,000 and in 2009 was 0.46 per 1,000.²⁶ SEARCH found that 5,758 children and adolescents ages 10 to 19 years were diagnosed with type 2 diabetes from 2014 to 2015, and the overall incidence of type 2 diabetes in 10- to 19-year-olds has increased significantly from an incidence rate of 0.09 per 1,000 in 2002 to 2003 to 0.14 per 1,000 in 2014 to 2015.³⁴

Most of that increase in the incidence rate is in nonwhite and non-Asian children and adolescents. The incidence rate in non-Hispanic white children remained stable between 0.04 and 0.05 children per 1,000 between 2002 and 2015 and for Asian/Pacific Islander children between 0.11 and 0.12 per 1,000 between 2002 and 2015. During the same time period, the incidence rate in non-Hispanic black children increased from 0.20 to 0.38 per 1,000, in Hispanic children the rate increased from 0.13 to 0.21 per 1,000, and in American Indian children (from primarily one southwestern tribe) the rate increased from 0.23 to 0.33 per 1,000.³⁴

Children who are obese and overweight are more likely to develop type 2 diabetes than peers who are underweight or who are at a healthy weight. This association between weight and diabetes is stronger in children than in adults.¹⁵ SEARCH data from 2001 to 2004 showed that about 80 percent of 400 children with type 2 diabetes were obese and 10 percent were overweight (compared with 17% of children without diabetes being obese).¹⁶

Type 2 diabetes is more common in older than younger children, often presenting at the onset of puberty.²⁷ It is estimated that, based on 2009 SEARCH data, 74 percent of pediatric type 2 diabetes cases are in youths ages 15 to 19 years, 23 percent are in those ages 10 to 14 years, and only 2 percent are in those ages 5 to 9 years.³³

In terms of burden of disease, diabetes (both type 1 and type 2) is the third most common chronic disease in childhood.³⁵ In all age groups (not limited to children and adolescents), diabetes was estimated to be the seventh leading cause of overall death in the United States in 2015 based on the Underlying Cause of Death database.³⁶ Approximately 3 percent of deaths (79,535 of 2,712,630 total deaths) were attributed to diabetes based on death certifications for U.S. residents. Cause of death was based on International Classification of Diseases, Tenth Revision codes, and estimates do not differentiate between type of diabetes. Morbidity from type 2 diabetes is due to both macrovascular disease (atherosclerosis) and microvascular disease (retinopathy, nephropathy, and neuropathy). Complications may begin in childhood or later in adulthood. Among those with type 2 diabetes diagnosed during childhood and adolescence, an estimated 19.9 percent, 9.1 percent, and 17.7 percent had complications of kidney disease, retinopathy, and peripheral neuropathy, respectively, during teenage years and young adulthood.³⁷ Diabetes is the leading cause of kidney failure, lower-limb amputations other than those caused by injury, and new cases of blindness among adults of all age groups in the United States.³⁸ Estimates based on results of the Global Burden of Disease Study indicate that diabetes was the third leading cause of years lived with disability in 2016, which is an approximate 30 percent increase from 1990 (when it ranked eighth).³⁹ In terms of causes of disability-adjusted life-years in the United States, diabetes ranked fourth in 2016, an increase from the sixth leading cause in 1990 (an approximate 11% change).³⁹

Rationale for Screening and Screening Strategies

Screening asymptomatic at-risk children and adolescents for prediabetes and type 2 diabetes may allow earlier detection, diagnosis, and interventions for both conditions, with the goal of improving health outcomes by preventing serious complications from type 2 diabetes. In children and adolescents, earlier detection of prediabetes may lead to interventions to prevent or delay progression to type 2 diabetes.⁴⁰ Early diagnosis of type 2 diabetes could potentially lead to earlier treatment to prevent diabetic complications.^41–44 Early diagnosis also may enable clinicians to treat patients with diabetes more effectively without requiring insulin. Strategies for screening for prediabetes and type 2 diabetes generally involve targeted screening of children who are overweight or obese for the presence of one or more risk factors (e.g., type 2 diabetes in a first- or second-degree relative, member of a high-risk racial/ethnic group, maternal history of diabetes or gestational diabetes) followed by fasting glucose, hemoglobin A1c, or OGTT.^{1, 45, 46}

Treatment Approaches

Clinical Practice in the United States and Recommendations of Other Organizations

In recent years, several U.S. and international professional organizations have issued recommendations for screening asymptomatic at-risk children and adolescents for prediabetes and type 2 diabetes (Appendix A Table 1). In 2020, the ADA published a position statement on managing youth-onset type 2 diabetes.⁴⁷ The ADA recommends risk-based screening for type 2 diabetes in children after onset of puberty or age 10 years who are overweight (BMI ≥85^th percentile) or obese (BMI ≥95^th percentile) and have one or more additional risk factors for diabetes. Such additional risk factors include maternal history of diabetes or gestational diabetes mellitus during the child’s gestation; family history of type 2 diabetes in first- or second-degree relative; being a member of a high-risk racial/ethnic group, including Native American, African American, Latino, Asian American, and Pacific Islander; or signs of insulin resistance or conditions associated with insulin resistance, including acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small-for-gestational-age birth weight.¹⁷ In terms of screening frequency, the ADA recommends screening to be repeated every 3 years if tests are normal or more frequently if BMI increases.⁴⁷ The ADA recommends testing with fasting plasma glucose, 2-h plasma glucose (PG) after 75-g OGTT, or an A1c. Further, the ADA recommends that children and adolescents who are overweight or obese for whom the diagnosis of type 2 diabetes is being considered have a panel of pancreatic autoantibodies tested to exclude the possibility of autoimmune type 1 diabetes.