Microsoft Word search phase 3 Title Page Amendment

Participant 
Survey (IPS) 
x 
x 
x 
x (for cases not 
incident in 
other years) 
x 
In-Person 
Visit (IPS) 
x x 
 
 
x 
(through 
September 
2010) 
Typology 
Visit 
 
 
x (2006 and 2008 
only) 
 
 

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Section 1 - Executive Summary (Phase 3 - 12/2010) 
Section 1 - Page 4 
 
Extended 
Typology 
x x 
 
 
 
 
12, 24, 60 
Month 
Follow-Up 
 x 
 
   
Annual 
follow-up for 
contact 
information 
x x 
x 
x 
  x 
 
SEARCH Phase 3 Objectives 
Five of the original six SEARCH 1 and 2 centers were funded to participate in SEARCH3: 
(Carolinas, Ohio, Colorado, California, and Washington).  The objectives of SEARCH Phase 3 
include a registry component and a cohort component.  Each component will be performed at all 
five clinical centers.  In SEARCH Phase 3, many of the measurements which were collected 
during SEARCH Phases 1 and 2 will continue to be collected; additionally, there will be unique 
measurements collected for each component of SEARCH Phase 3. 
Registry Study 
The SEARCH for Diabetes in Youth Registry Study will continue to ascertain newly diagnosed 
incident diabetes cases in youth age < 20 years across five geographically dispersed Study 
Centers in order to accomplish the Specific Aims shown below.  The study will continue to 
identify incident cases from September 30, 2010 through September 29, 2015, and will 
periodically re-ascertain cases from earlier years. 
Aim 1:  To continue to ascertain newly diagnosed (2010 - 2014) incident diabetes cases in 
youth age < 20 years in order to assess temporal trends in diabetes incidence and temporal 
trends in presentation of diabetes for the period 2002-2014, by age, sex, race/ethnicity, and 
diabetes type. 
Specific characteristics to be examined are: age at onset of diabetes, markers of disease 
severity (diabetic ketoacidosis, residual insulin secretion, HbA
1c
), immunogenetic markers 
(diabetes autoantibodies, HLA risk genotypes), markers of insulin sensitivity (insulin 
sensitivity score, waist circumference, body mass index), cardiovascular risk factors (lipid 
profile, blood pressure, microalbuminuria). 
Aim 2:  To provide consultation and support to inform the development of low-cost 
sustainable public health surveillance systems of childhood diabetes in the U.S., with a focus 
on challenges in ascertainment of cases with T2D and cases among older youth (ages 15 
years or older) with any form of non-gestational diabetes.  

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Section 1 - Executive Summary (Phase 3 - 12/2010) 
Section 1 - Page 5 
 
Aim 3:  Assess total and cause-specific mortality among 2002-2008 incident cases for the 
period from the date of diabetes diagnosis through December 31, 2010.   
Cohort Study 
An in-person research visit with SEARCH participants incident in 2002 or later, with a duration 
of diabetes > 5 years, and with data from a baseline study visit (expected n=3,699).  SEARCH 
has a well-established and ongoing infrastructure and is uniquely positioned to successfully 
address the following Aims: 
Aim 1:  Assess the prevalence and incidence of, and risk factors for chronic microvascular 
(retinopathy, nephropathy, and autonomic neuropathy) and selected markers of 
macrovascular complications (hypertension, arterial stiffness) of diabetes. 
Aim 2:  Assess the incidence of, and risk factors for, serious acute complications of diabetes 
including severe hypoglycemia and diabetic ketoacidosis (DKA). 
Aim 3:  Determine the degree to which barriers to care, quality of care, and the process of 
transition from pediatric to adult care impact disease factors, including dimensions of 
diabetes type (e.g., diabetes autoimmunity, insulin sensitivity), and diabetes-related outcomes 
(acute and chronic complications, quality of life, diabetes-related mortality). 
Aim 4:  Maintain and supplement the SEARCH repository for biological specimens, and 
promote access to SEARCH for conduct of scientifically and logistically appropriate 
ancillary studies. 

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Section 1 - Executive Summary (Phase 3 - 12/2010) 
Section 1 - Page 6 
 
Reference List 
 
1.
 
Gungor, N., et al., Youth type 2 diabetes: insulin resistance, beta-cell failure, or both? 
Diabetes Care, 2005. 28(3): p. 638-44. 
2.
 
Gungor, N., et al., Type 2 diabetes mellitus in youth: the complete picture to date. Pediatr 
Clin North Am, 2005. 52(6): p. 1579-609. 
3.
 
Druet, C., et al., Characterization of insulin secretion and resistance in type 2 diabetes of 
adolescents. J Clin Endocrinol Metab, 2006. 91(2): p. 401-4. 
4.
 
Kahn, H.S. and R. Valdez, Metabolic risks identified by the combination of enlarged waist 
and elevated triacylglycerol concentration. Am J Clin Nutr, 2003. 78(5): p. 928-34. 
5.
 
Dabelea, D., et al., Incidence of diabetes in youth in the United States. JAMA, 2007. 297(24): 
p. 2716-24. 
6.
 
The DIAMOND Project Group. Incidence and trends of childhood Type 1 diabetes 
worldwide 1990-1999. Diabet Med, 2006;23:857-66. 
7.
 
Patterson, C.C., et al., Incidence trends for childhood type 1 diabetes in Europe during 1989-
2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet, 
2009. 373(9680): p. 2027-33. 
8.
 
Ogden, C.L., et al., Prevalence and trends in overweight among US children and adolescents, 
1999-2000, JAMA, 2002. 288(14): p. 1728-32. 
9.
 
Dahlquist, G. and B. Kallen, Mortality in childhood-onset type 1 diabetes: a population-based 
study. Diabetes Care, 2005. 28(10): p. 2384-7. 
10.
 
Patterson, C.C., et al., Early mortality in EURODIAB population-based cohorts of type 1 
diabetes diagnosed in childhood since 1989. Diabetologia, 2007. 50(12): p. 2439-42. 
11.
 
Rewers, M., Why do people with diabetes die too soon? More questions than answers. 
Diabetes Care, 2008. 31(4): p. 830-2. 
12.
 
Krakoff, J., et al., Incidence of retinopathy and nephropathy in youth-onset compared with 
adult-onset type 2 diabetes. Diabetes Care, 2003. 26(1): p. 76-81. 
13.
 
Pavkov, M.E., et al., Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage 
renal disease and mortality in young and middle-aged Pima Indians. JAMA, 2006. 296(4): p. 
421-6. 
14.
 
Narayan, K.M., et al., Lifetime risk for diabetes mellitus in the United States. JAMA, 2003. 
290(14): p. 1884-90. 

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SEARCH Phase 3 Protocol - Section 2 
Center Descriptions 
Table of Contents