Final Research Plan

Prediabetes and Type 2 Diabetes in Children and Adolescents: Screening

November 12, 2020

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

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• Figure 1 depicts the key questions within the context of the eligible populations, screenings/interventions, comparisons, outcomes, and settings. On the left, the population of interest is asymptomatic children and adolescents. Moving from left to right, the figure illustrates the overarching question: Is there direct evidence that screening for type 2 diabetes and prediabetes in asymptomatic children and adolescents improves health outcomes (KQ 1)? Screening may result in harms (KQ 2). After diagnosis of type 2 diabetes or prediabetes, the figure illustrates the following questions: Do interventions provide an incremental benefit in health outcomes when delivered at the time of detection compared with initiating interventions later, after clinical diagnosis (KQ 3a); and do interventions improve health outcomes compared with no intervention, usual care, or interventions with different treatment targets (KQ 3b)? For recently diagnosed type 2 diabetes, the figure illustrates the question: Do interventions improve health outcomes compared with no intervention, usual care, or interventions with different treatment targets (KQ 3c)? Interventions may result in harms (KQ 4). For prediabetes, the figure depicts the questions: Do interventions delay or prevent progression to type 2 diabetes (KQ 5); and after intervention, what is the magnitude of change in health outcomes that results from the reduction in type 2 diabetes incidence (KQ 6)?

* Eligible interventions include pharmacotherapy and primary care–relevant counseling focused on healthy diet and nutrition, physical activity, or both, as detailed in the Research Approach below.

1.  Is there direct evidence that screening for type 2 diabetes mellitus (T2DM) and prediabetes in asymptomatic children and adolescents improves health outcomes?
2.  What are the harms of screening for T2DM and prediabetes in asymptomatic children and adolescents?
3.  a. Do interventions for screen-detected T2DM and prediabetes provide an incremental benefit in health outcomes when delivered at the time of detection compared with initiating interventions later, after clinical diagnosis?
     b. Do interventions for screen-detected T2DM and prediabetes improve health outcomes compared with no intervention, usual care, or interventions with different treatment targets?
     c. Do interventions for recently diagnosed T2DM improve health outcomes compared with no intervention, usual care, or interventions with different treatment targets?
4.  What are the harms of interventions for prediabetes, screen-detected T2DM, or recently diagnosed T2DM?
5.  Do interventions for prediabetes delay or prevent progression to T2DM?
6.  After interventions for prediabetes are provided, what is the magnitude of change in health outcomes that results from the reduction in T2DM incidence?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

1. a. What percentage of children and adolescents with prediabetes progress to T2DM, remain prediabetic, or return to normal glycemia or glucose tolerance (without intervention), and over what time frame?
    b. What percentage of children and adolescents with T2DM return to normal glycemia or glucose tolerance or to the prediabetes range (without intervention), and over what time frame?
    c. How does this differ by baseline hemoglobin (Hb) A1c level, fasting glucose level, or glucose tolerance?
2. a. Does screening for prediabetes or T2DM change the intermediate outcomes of HbA1c level, fasting plasma glucose level, 2-hour glucose tolerance test results, subclinical retinopathy, microalbuminuria, or subclinical neuropathy for children and adolescents?
   b. Do interventions for children and adolescents with screen-detected or recently diagnosed T2DM or prediabetes change the intermediate outcomes of HbA1c level, fasting plasma glucose level, 2-hour glucose tolerance test results, subclinical retinopathy, microalbuminuria, or subclinical neuropathy?
3. a. Do interventions for (or does knowledge of) prediabetes change body mass index, weight, or healthy behaviors?
    b. Do interventions for (or does knowledge of) T2DM change body mass index, weight, or healthy behaviors?
4. What is the frequency of agreement among screening tests (HbA1c level, fasting plasma glucose level, and 2-hour glucose tolerance test) for prediabetes and T2DM?
5. Are there risk assessment tools that are feasible for use in primary care settings, accurately predict the risk of prediabetes or T2DM for children and adolescents, and have been externally validated in U.S. populations?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions.

Criteria Include Exclude
Populations All KQs: Studies of children and adolescents younger than age 18 years; studies of participants without obvious symptoms of diabetes (e.g., for KQ 1, studies of unselected populations that may include some participants with unrecognized symptoms of diabetes such as fatigue); nonpregnant persons with a history of gestational diabetes (if they are >1 year postpartum); studies that substantially overlap this age range (e.g., ages 14 to 65 years) will be included if results for younger participants are reported separately. At least 50% of the study population must meet the review eligibility criteria or results must be reported separately for the population eligible for the review.

KQs 1, 2: Asymptomatic, nonpregnant children and adolescents.

KQs 3, 4: Asymptomatic, nonpregnant children and adolescents with screen-detected prediabetes or T2DM (KQs 3a and 3b) or with recently diagnosed T2DM (KQ 3c); studies of persons with maturity-onset diabetes of the young (MODY) are also eligible.

KQs 5, 6: Asymptomatic, nonpregnant children and adolescents with screen-detected prediabetes.

Subgroups: Studies that examine whether effectiveness of screening or intervention differs based on age, sex, race/ethnicity, body mass index, sexual maturity rating, age of menarche, and socioeconomic status will be examined.

 KQs 1–6: Studies limited to or predominately comprising adults or pregnant women; persons with symptomatic prediabetes or T2DM (e.g., weight loss, polyuria, blurred vision, headache); persons with a recent hospitalization; persons taking antipsychotics or glucocorticoids; persons with known cardiovascular disease or severe chronic kidney disease; persons living in an institution; other persons with medical conditions limiting their applicability to primary care–based populations (e.g., those with acute illness).

KQ 3c: Studies limited to or predominately comprised of persons who have had diabetes for more than 1 year or with more advanced diabetes (e.g., persons already taking insulin or other medications; persons with proliferative retinopathy, nephropathy).
Screening KQs 1, 2: Screening (targeted or universal) for prediabetes* or diabetes; tests include hemoglobin A1c, FPG, and the OGTT. All other tests, such as genetic testing for the risk of prediabetes or diabetes or testing for autoantibodies, which may be used for further evaluation after a diabetes diagnosis (e.g., to assess for type 1 or type 2 diabetes).
Interventions KQs 3–6: Primary care–relevant behavioral counseling or pharmacotherapy interventions for glycemic control.
Behavioral counseling interventions can be provided alone or as part of a larger multicomponent intervention on diet and nutrition, physical activity, sedentary behavior, or a combination thereof, including but not limited to assessment with feedback, advice, collaborative goal setting, assistance, exercise prescriptions (referral to exercise facility or program), or arrangement of further contacts.

Interventions may be delivered via face-to-face contact, telephone, print materials, or technology (e.g., computer-based, text messages, remote video feed) and can be delivered by a number of potential interventionists, including but not limited to clinicians, nurses, exercise specialists, dietitians, nutritionists, and behavioral health specialists.

Dietary counseling may involve:

  • Increased consumption of fruits, vegetables, whole grains, fat-free or low-fat dairy, and/or lean proteins
  • Limited consumption of sodium, saturated fat, trans fat, and/or sugar-sweetened food and beverages

Physical activity counseling may involve:

  • Aerobic activities that involve repeated use of large muscles, such as walking, cycling, and swimming
  • Resistance training designed to improve physical strength
  • Reduction of sedentary behaviors
  • Optional or access to guided physical activity or exercise classes
Limited guided physical activity (i.e., one to two sessions) or provision of food samples is allowed if intention is to teach or demonstrate healthy lifestyle principles.
  • Counseling interventions aimed at depression
  • Prenatal or postnatal dietary counseling
  • Counseling interventions with components that are not feasible for implementation in health care settings (e.g., occupational/worksite-, church-, or school-based interventions conducted within existing social networks)
  • Social marketing (e.g., media campaigns)
  • Policy (e.g., local or state public/health policy)
  • Stress management interventions (e.g., meditation, yoga, tai chi)
  • Use of incentives (e.g., paying persons to lose weight)
  • Supervised exercise with the goal of assessing effects of exercise
  • Dietary counseling solely focused on increasing intake of specific vitamins, micronutrients, herbal supplements, spices (e.g., ginger, cinnamon), or antioxidants through dietary change or supplementation, or counseling on alcohol
  • Surgery
Comparisons KQs 1, 2: No screening or alternative screening strategies.

KQ 3a: Comparison based on timing; sooner vs. later intervention (i.e., starting intervention upon detection by screening vs. starting later based on clinical diagnosis); clinical diagnosis refers to any approach based on development of symptoms (e.g., polyuria, polydipsia, paresthesia, vision changes) or monitoring of biomarkers (e.g., increase in hemoglobin A1c level above a certain threshold).

KQs 3b, 3c: No intervention, placebo, usual care (can include minimal intervention), different treatment targets (e.g., glucose or blood pressure targets), waitlist, or attention control (for lifestyle interventions).

KQ 4: All comparisons eligible for KQ 3.

KQs 5, 6: Sooner vs. later intervention, no intervention, placebo, usual care, waitlist, or attention control (for lifestyle interventions).		 Comparative effectiveness (head-to-head) trials of medications or behavioral counseling without another eligible control group.
Outcomes KQs 1, 3, 6: Mortality, cardiovascular morbidity (including myocardial infarction, stroke, congestive heart failure), chronic kidney disease, amputation, skin ulcers, visual impairment (including blindness), periodontitis (including tooth loss), moderate to severe neuropathy, and quality of life.

KQ 2: Labeling, anxiety, harms from false-positive results, burden, inconvenience, depression, and unnecessary testing and treatment.

KQ 4: Serious side effects from treatment, including gastrointestinal side effects, mortality, myocardial infarction, stroke, cancer, and hypoglycemic events requiring medical attention; burden and inconvenience.

KQ 5: Development of T2DM.		 KQs 1, 3, 5, 6: Studies with less than 6 months of followup.
Study Designs All KQs: Controlled clinical trials.

KQs 2, 4: Controlled prospective cohort studies and case-control studies are also eligible.

KQ 6: Controlled prospective cohort studies are also eligible.		 Modeling studies, systematic reviews,** case series, case reports, uncontrolled observational studies, retrospective cohort studies, editorials, and all other study designs not mentioned.
Settings Studies conducted in or recruited from primary care settings or settings otherwise applicable to primary care, including school-based health centers and other community settings that provide primary care or are referable from primary care (i.e., screening/interventions that could feasibly be implemented in or referred from primary care). Settings not generalizable to primary care (e.g., inpatient hospital units, emergency departments, nursing home and other institutional settings, school-based curricula or programs that are not referable from primary care, occupational settings).
Countries Studies conducted in countries categorized as “Very High” on the Human Development Index in the 2019 Human Development Report (as defined by the United Nations Development Programme). Studies conducted in countries that are categorized as lower than “Very High” on the Human Development Index in the 2019 Human Development Report.
Language English Languages other than English
Study Quality Good or fair Poor (according to design-specific USPSTF criteria)

* Prediabetes includes individuals who meet criteria for IFG or IGT and those with a HbA1c level from 5.7% to 6.4%.
** Systematic reviews will be excluded from the evidence review. However, separate searches will be conducted to identify relevant systematic reviews, and the citations of all studies included in those systematic reviews will be reviewed to ensure that the database searches have captured all relevant primary studies.

Abbreviations: HbA1c=glycated hemoglobin; FPG=fasting plasma glucose; IFG=impaired fasting glucose; IGT=impaired glucose tolerance; KQ=key question; OGTT=oral glucose tolerance test; T2DM=type 2 diabetes mellitus; USPSTF=U.S. Preventive Services Task Force.

The draft Research Plan was posted on the USPSTF website for public comment from July 30, 2020, to August 26, 2020. In response to public comments, the USPSTF changed the title to include prediabetes, added socioeconomic status to the list of prespecified subgroups, clarified the eligibility of school-based health centers and community settings, and added more intermediate outcomes to the contextual questions.