Final Research Plan

Prediabetes and Type 2 Diabetes: Screening

November 15, 2018

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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The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from July 5 until August 1, 2018 at 8:00 p.m., ET.

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 nonpregnant adults without symptoms or a diagnosis of diabetes. 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 adults improves health outcomes (KQ1)? Screening may result in harms (KQ2). 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 (KQ3), and do interventions improve health outcomes compared with no intervention, usual care, or an intervention with different treatment targets (KQ4)? For recently diagnosed type 2 diabetes, the figure illustrates the question: Do interventions improve health outcomes compared with no intervention, usual care, or an intervention with different treatment targets (KQ5)? Interventions may result in harms (KQ6). For prediabetes, the figure depicts the questions: Do interventions delay or prevent progression to type 2 diabetes (KQ7), and what is the magnitude of change in health outcomes that results from a specified change in type 2 diabetes incidence after intervention (KQ8)? The figure also depicts the question: Do interventions for prediabetes improve other intermediate outcomes (blood pressure, lipid levels, BMI, weight, and calculated 10-year cardiovascular disease risk) (KQ9)?

* Eligible interventions include pharmacotherapy and primary care–relevant behavioral counseling focused on healthy diet and nutrition, physical activity, or both, as detailed in the Research Approach below.
† Other intermediate outcomes include blood pressure, lipid levels, body mass index, weight, and calculated 10-year cardiovascular disease risk.

1. a. Is there direct evidence that screening for type 2 diabetes and prediabetes in asymptomatic adults improves health outcomes?
    b. Does the effectiveness of screening differ for subgroups defined by age, sex, race/ethnicity, socioeconomic status, or body mass index (BMI)?
2. a. What are the harms of screening for type 2 diabetes and prediabetes in asymptomatic adults?
    b. Do the harms of screening differ for subgroups defined by age, sex, race/ethnicity, socioeconomic status, or BMI?
3. a. Do interventions for screen-detected type 2 diabetes 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. Does the effectiveness of these interventions differ for subgroups defined by age, sex, race/ethnicity, socioeconomic status, or BMI?
4. a. Do interventions for screen-detected type 2 diabetes and prediabetes improve health outcomes compared with no intervention, usual care, or interventions with different treatment targets?
    b. Does the effectiveness of these interventions differ for subgroups defined by age, sex, race/ethnicity, socioeconomic status, or BMI?
5. a. Do interventions for recently diagnosed type 2 diabetes improve health outcomes compared with no intervention, usual care, or interventions with different treatment targets?
    b. Does the effectiveness of these interventions differ for subgroups defined by age, sex, race/ethnicity, socioeconomic status, or BMI?
6. What are the harms of interventions for prediabetes, screen-detected type 2 diabetes, or recently diagnosed type 2 diabetes?
7. a. Do interventions for prediabetes delay or prevent progression to type 2 diabetes?
    b. Does the effectiveness of these interventions differ for subgroups defined by age, sex, race/ethnicity, socioeconomic status, or BMI?
8. After interventions for prediabetes are provided, what is the magnitude of change in health outcomes that results from the reduction in type 2 diabetes incidence?
9. Do interventions for prediabetes improve other intermediate outcomes (blood pressure, lipid levels, BMI, weight, and calculated 10-year cardiovascular disease risk)?

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

  1. Are there risk assessment tools that are feasible for use in primary care settings, accurately predict the risk of prediabetes or type 2 diabetes, and have been externally validated in U.S. populations?
  2. What is the frequency of agreement among screening tests* for prediabetes and diabetes?
  3. Which of these screening tests* best predicts future adverse health outcomes associated with type 2 diabetes?
  4. What is the yield (i.e., incidence of prediabetes or diabetes) of rescreening at different intervals in adults with an initial normal screening test* result?
  5. What is the utility of recently published modeling studies that assess screening for type 2 diabetes and prediabetes (vs. no screening) in examining health outcomes?

*Screening tests under consideration include hemoglobin A1c, fasting plasma glucose, and the oral glucose tolerance test.

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 (KQs).

Category Include Exclude
Populations All KQs: 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 women with a history of gestational diabetes (if they are >1 year postpartum)

KQs 1, 2: Asymptomatic, nonpregnant adults

KQs 3, 4: Asymptomatic, nonpregnant adults with screen-detected prediabetes or type 2 diabetes

KQ 5: Asymptomatic, nonpregnant adults with recently diagnosed type 2 diabetes

KQ 6: Asymptomatic, nonpregnant adults with screen-detected prediabetes or type 2 diabetes; nonpregnant adults with recently diagnosed type 2 diabetes

KQs 7–9: Asymptomatic, nonpregnant adults with screen-detected prediabetes

 All KQs: Studies limited to or predominately comprised of children, adolescents, and pregnant women; persons with symptomatic prediabetes or type 2 diabetes (e.g., weight loss, polyuria, blurred vision, headache); persons with a recent hospitalization; persons with a recent myocardial infarction; 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 5: 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, fasting plasma glucose, and the oral glucose tolerance test

 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 All KQs: 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 arranging 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., 1 to 2 sessions) or provision of food samples is allowed if intention is to teach or demonstrate healthy lifestyle principles

KQs 3–6: Primary care–relevant behavioral counseling or pharmacotherapy interventions for glycemic control or for more intensive risk reduction of atherosclerotic cardiovascular disease, including more intensive blood pressure control, lipid control, or aspirin

KQs 7–9: Primary care–relevant behavioral counseling or pharmacotherapy interventions for glycemic control
  • Counseling interventions aimed at falls prevention, balance, flexibility, gait, depression, or cognitive functioning
  • 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 moderation
  • Surgery
Comparisons KQs 1, 2: No screening or alternative screening strategies

KQ 3: 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) or monitoring of biomarkers (e.g., increase in hemoglobin A1c above a certain threshold)

KQs 4, 5: No intervention, placebo, usual care (can include minimal intervention), different treatment targets (e.g., glucose or blood pressure targets), or attention controls (for lifestyle interventions)

KQ 6: All comparisons eligible for KQs 3–5

KQs 7–9: Sooner vs. later intervention, no intervention, placebo, usual care, waitlist, or attention controls (for lifestyle interventions)

 Comparative effectiveness (head-to-head) trials of medications or behavioral counseling without another eligible control group
Outcomes
KQs 1, 3–5, 8: 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 6: Serious side effects from treatment, including mortality, myocardial infarction, stroke, cancer, and hypoglycemic events requiring medical attention; burden and inconvenience

KQ 7: Development of type 2 diabetes

KQ 9: Blood pressure; total, low-density lipoprotein, and high-density lipoprotein cholesterol; BMI, weight; calculated 10-year cardiovascular disease risk
KQs 1, 3-5, 7–9: Studies with less than 6 months of followup
Study Designs All KQs: Controlled clinical trials

KQs 2, 6: Controlled prospective cohort studies and case-control studies are also eligible

KQ 8: 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 (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 programs, occupational settings)
Countries Studies conducted in countries categorized as “Medium” or higher on the 2016 Human Development Index (as defined by the United Nations Development Programme) Studies conducted in countries that are not categorized as “Medium” or higher on the 2016 Human Development Index
Language English language Languages other than English
Study quality Good- or fair-quality Poor-quality (according to design-specific USPSTF criteria)

* Prediabetes includes persons who meet criteria for impaired fasting glucose or impaired glucose tolerance and persons with an A1c level of 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.

The draft Research Plan was posted for public comment on the USPSTF Web site from July 5, 2018 to August 1, 2018. In response to comments, the USPSTF made the following changes: 1) added a KQ about other intermediate outcomes after intervention for prediabetes (KQ 9), 2) clarified the types of eligible interventions, 3) added socioeconomic status to the subgroups listed in the KQs, 4) clarified that women with a history of gestational diabetes are eligible, 5) revised the terminology used to describe counseling interventions (including revisions for consistency with other topics in the USPSTF portfolio), 6) expanded the list of eligible outcomes, 7) clarified that eligible study settings include those in which screening and interventions could feasibly be implemented in or referred from primary care, and 8) explained that genetic testing and autoantibody testing are not within the scope of the review.