The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000 to address major knowledge gaps in the understanding of childhood diabetes. The SEARCH study (SEARCH 1-3) was conducted at five sites across the U.S. and established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. The cohort study (SEARCH 4) was developed by recruiting incident cases in 2002 to 2006, 2008, and 2012 that had a baseline visit near diagnosis and at least 5 years of diabetes duration at the cohort visit assessment. In the first two phases of SEARCH (SEARCH 1 and 2), individuals newly diagnosed with diabetes in 2002– 2006 and 2008 were recruited for a baseline research visit. Incident cases from 2002–2005 were also asked to return for visits at 12, 24, and 60 months after their baseline visit to measure risk factors for diabetes complications. In the third phase (SEARCH 3), a subset of SEARCH participants with a duration of diabetes >5 years were recruited for an outcome visit between 2011 and 2015. In addition, individuals incident in 2012 were invited for a baseline visit. In the fourth phase (SEARCH 4), a subset of SEARCH participants aged >10 years with at least 5 years of diabetes duration were invited to another study visit between 2015 and 2019. Those invited to the in-person research visit included all individuals with type 2 diabetes, all non-Whites, and a random sample of non-Hispanic Whites with type 1 diabetes.

Note: Specimens are available from SEARCH 4 only.

The objectives of the SEARCH study were to conduct longitudinal follow-up of youth with diabetes in order to:

• Document the evolution of newly diagnosed diabetes according to clinical and biochemical factors
• Characterize the evolution of key risk factors for diabetes complications, according to diabetes type and race/ethnicity
• Assess the impact of quality of diabetes care in youth on short- and long-term outcomes including quality of life
• Determine the degree to which barriers to care, quality of care, and the process of transition from pediatric to adult care impact diabetes-related outcomes (e.g., acute and chronic complications, quality of life, diabetes-related mortality)
• Establish, compare, and contrast the burden (prevalence, incidence, progression, and clustering) of acute and chronic complications of diabetes, and explore the responsible risk factors and pathways among youth and young adults with type 1 and type 2 diabetes

The SEARCH study measured key outcomes including retinopathy, nephropathy, neurocognitive function, cardiac echocardiography, cardiac autonomic and peripheral neuropathy, arterial stiffness, cardiac damage, as well as acute complications (e.g., hypoglycemia, diabetic ketoacidosis (DKA)). In addition, the study collected information on health history; treatments and medications; behavioral, psychosocial, and socio-cultural factors, quality of life; processes, quality, and barriers to care; and transition to adult care.

Inclusion criteria:

• Diagnosed with diabetes
• Less than 20 years of age
• Resident of defined geographic region (geographic centers) or member of defined insurance organization (health plan centers)

The SEARCH study found that over 50% of youth were hospitalized at diabetes onset, and 30% of children newly diagnosed with diabetes presented with diabetic ketoacidosis (DKA). Prevalence of DKA at diagnosis was three times higher among youth with type 1 diabetes (29.4%) compared with youth with type 2 diabetes (9.7%), and was lowest in Asian/Pacific Islanders (16.2%) and highest among Hispanics (27.0%). While there were high levels of adherence for some diabetes care indicators such as blood pressure checks (95%), urinary protein tests (83%), and lipid assessments (88%), approximately one-third of youth had no documentation of eye exams or A1C values at appropriate intervals and, therefore, were not meeting the American Diabetes Association (ADA) recommended screening for diabetes control and complications. Participants 18 years old, particularly those with type 2 diabetes, and minority youth with type 1 diabetes had fewer tests of all kinds performed. Challenges in the transition from pediatric to adult care were also observed. There was a 2.5 times greater odds of poor glycemic control among youth with type 1 diabetes transitioning to adult care compared with those who remained in pediatric care, suggesting that this period requires a high level of support to ensure success. Importantly, using basal-bolus therapies and higher frequency of glucose monitoring were associated with lower A1C in youth with type 1 diabetes. SEARCH demonstrated that the prevalence of diabetes-related complications was higher among those with type 2 diabetes than with type 1 at equivalent HbA1c levels, but the prevalence was substantial in both groups. At an estimated age of 21 years and after 7.9 years’ mean diabetes duration, approximately 1 in 3 teenagers and young adults with type 1 diabetes (32%) and almost 3 of 4 of those with type 2 diabetes (72%) had at least 1 complication or comorbidity.