The SEARCH for Diabetes in Youth Study: Rationale, Findings, and Future Directions
Article Figures & Tables
Figures
- Figure 1
Summary of the SEARCH study design. The registry began in 2001 measuring prevalence, which was repeated in 2009. Incidence has been measured annually starting in 2002. Youth diagnosed in 2002–2006, 2008, and 2012 had a baseline in-person visit for measurement of diabetes autoantibodies, albuminuria, BMI, cardiovascular risk factors, and sociodemographic, quality of care, and quality of life questionnaires. Youth with baseline visits (incident cases in 2002–2005) were invited to return in 12, 24, and 60 months after their baseline visit for additional visits. Those with a baseline visit and at least 5 years of duration were asked to join the cohort study, started in 2012, which added measures of early complications (retinopathy, cardiac autonomic and peripheral neuropathy, and arterial stiffness). Future follow-up of the cohort is planned.
- Figure 2
Prevalence (per 1,000) of diabetes by type, sex, age group, and race/ethnic group in 2001 and 2009 (2). P values for change between years: *P < 0.05; **P < 0.01; ***P < 0.001. AA, African American; AI, American Indian; API, Asian Pacific Islander; HISP, Hispanic; NHW, non-Hispanic white.
- Figure 3
Proposed algorithm for classification of pediatric diabetes. Presence of any antibodies indicates type 1 diabetes. Absence of antibodies and a large waist [or insulin sensitivity score <8.15 units (47)] indicates type 2 diabetes. Individuals with no antibodies and a normal waist (or insulin sensitivity score ≥8.15 units) require additional testing for potential monogenic forms of diabetes or other defects. GADA, GAD antibody; IAA, insulin autoantibody; MODY, maturity-onset diabetes of the young.
Tables
- Table 1
Prevalence of elevated glycemia, CVD risk factors, and early complications, SEARCH 2006–2013
Type 1 P value Type 2 P value Glycemia (28) N = 3,947 N = 552 A1C ≥9.5% (≥80 mmol/mol), all races (%) 16.8 26.6 Non-Hispanic white 12.3 <0.0001* 12.2 <0.0001* African American 35.5 22.3 Hispanic 27.3 27.4 Asian Pacific Islander 26.0 36.4 American Indian 52.2 43.8 CVD risk factors†, age 10–19 years (30) N = 1,376 N = 63 Hypertension (%) 22.0 73.0 Elevated triglycerides (%) 14.0 65.0 Decreased HDL (%) 9.0 60.0 Increased waist circumference (%) 15.0 95.0 N = 2,657 N = 345 Elevated apoB (%) (32) 10.6 36.3 <0.0001‡ Dense LDL (%) (32) 7.9 36.3 Retinopathy (34) N = 222 N = 43 Any (%) 17.0 42.0 0.40‡ Mild/moderate/proliferative (%) 2.7 16.3 Nephropathy (33) N = 2,885 N = 374 Elevated ACR ≥30 μg/mg (%) 9.2 22.2 <0.0001‡ Neuropathy N = 329 N = 70 Peripheral neuropathy MNSE >2 (%) (35) 8.2 25.7 <0.0001‡ Heart rate variability (%) (36) −11.6 0.003†† Arterial stiffness (37) N = 535 N = 60 Pulse wave velocity (m/sec) 5.3 6.4 <0.01‡ BrachD (%/mmHg) 6.1 5.2 <0.01‡ ACR, albumin/creatinine ratio; BrachD, brachial distensibility (lower is stiffer); CVD, cardiovascular disease; MNSE, Michigan neuropathy screening examination; pulse wave velocity, carotid to femoral (higher is stiffer).
↵*Within type of diabetes.
↵†Hypertension: diastolic blood pressure ≥90th percentile for age, sex, and height or taking medication for high blood pressure; triglycerides ≥110 mg/dL; HDL ≤40 mg/dL; waist ≥90th percentile for age, sex, and height; apoB ≥100 mg/dL; dense LDL, relative flotation rate ≤0.237.
↵‡Between type of diabetes.
↵††Compared with nondiabetic control subjects, N = 354 type 1; 176 control subjects.
- Table 2
Major topics and papers from the SEARCH study and ancillary studies*
Burden of diabetes (prevalence/1,000) 2001 (5); 2009 (6); changes in prevalence 2001–2009 (2); projections of diabetes burden to 2050 (50) Risk of diabetes (incidence/100,000) 2002 to 2003 (12); 2008 to 2009 (13); trends in incidence, non-Hispanic whites (2002–2009) (14) Race/ethnicity–specific characteristics Navajo (21); Asian, Pacific Islander (23); Hispanic (22); African American (24); non-Hispanic white (20) Adiposity Prevalence of overweight and obesity (25) Weight-loss practices and weight-related issues (58) Clinical, biochemical, and genetic findings Glycemic control Lipids and glycemic control (59) Glycemic control and change in lipids (61) Psychosocial burden and glycemic control (63) HLA and genetics HLA-associated phenotypes (60) Time trends in HLA susceptibility among type 1 in Colorado (62) Prevalence of MODY due to HNF1A, HNF4A, glucokinase (48), JDRF Monogenic Study* Prevalence of permanent neonatal diabetes (64), JDRF Monogenic Study* TCF7L2 and type 2 in multiethnic youth (66) β-Cell function Preservation of β-cell function in autoantibody positive youth (65) Evolution of β-cell function (67) Testing the accelerator hypothesis: body size, β-cell function, age at onset among type 1 (68) Type of diabetes Development of an insulin sensitivity score (46) Etiologic approach to characterization of diabetes type (47) CVD risk factors CVD risk factor clustering (69) Prevalence of elevated apoB and small, dense LDL (32) Lipids among type 1 and control subjects (71), SEARCH CC* CVD risk factors among type 2 and controls (73), SEARCH CC* Prevalence of tobacco use and CVD risk factors (75) Developmental origins Maternal diabetes in utero and age at diagnosis among type 2 (70) Maternal obesity and diabetes in utero and type 2 (72), SEARCH CC* Breast-feeding and type 2 in three ethnic groups (74), SEARCH CC* Behavioral factors Physical activity and self-concept (76), SEARCH CC* Physical activity and electronic media use (26), SEARCH CC* TV and computer use (79) Cardiovascular health among type 1 (81), SEARCH CVD* Nutrition Dietary intake (27) Correlates of dietary intake (77) DASH diet and CVD risk factors (78) Change in DASH diet and CVD risk factors (80) Sugar sweetened beverages and CVD risk profile (82) DASH diet and hypertension (83) Vitamin D insufficiency prevalence and association with insulin resistance (85), SNAS* Nutritional factors and preservation of C-peptide among type 1 (87), SNAS* Fructose intake and CVD risk factors among type 1 (89), SNAS* Dietary intake patterns and arterial stiffness (91), SNAS* and CVD* Quality of life Health-related quality of life (84) Demographic and clinical correlates of quality of life among type 1 (86) Longitudinal associations among sex, self-care, and quality of life (88) Prevalence and correlates of depressed mood (90) Metabolic and inflammatory links with depression (92) Acute complications Prevalence of DKA at onset (19) Trends in DKA at onset (44) Risk factors and early complications Carotid structure and function among type 1 (39), SEARCH CVD* CVD risk factors associated with increased arterial stiffness among type 1 (93), SEARCH CVD* Smoking and arterial stiffness among type 1 (95), SEARCH CVD* Reduced HRV in type 1 and control subjects (36), SEARCH CVD* Glycemic control and HRV (94), SEARCH CVD* Reduced HRV is associated with increased arterial stiffness among type 1 (96), SEARCH CVD* Quality of care Barriers to care among type 1 (97) Treatment patterns among type 2 (99) Transition from childhood to adult care among type 1 (41) Insulin regimens and clinical outcomes (42) Predictors of insulin regimens among type 1 (102) Spatial epidemiology and built environment Neighborhood level risk factors among type 1 (98), SPATIAL* Geographic variation in type 1 and 2 in four U.S. regions (100) Surveillance Ascertainment of diabetes using EHRs (54,101) Adherence to treatment guidelines (40) Studies shown in Table 1 are not included in Table 2. CVD, cardiovascular disease; DASH, Dietary Approaches to Stop Hypertension; HRV, heart rate variability.
↵*Ancillary studies include SEARCH Case-Control (CC); SEARCH CVD; Juvenile Diabetes Research Foundation (JDRF) Monogenic Study; SEARCH Nutrition Ancillary Study (SNAS); and SEARCH Spatial Epidemiology of Diabetes (SPATIAL).
In this Issue
