Microsoft Word search phase 3 Title Page Amendment

 
 
 
 
 
 
 
Mediators 
 
Barriers to Care 
Quality of Care 
Transition of Care 
Behavioral Risk Factors 
Psychosocial Factors 
Biological Risk
Factors
 
 
 
 
 
Dimensions of 
Diabetes
 
Type
 
 
CVD Risk Profile
 
 
Figure 3
 
 
 
 
 
SEARCH Cohort StudyConceptual model
  
Outcomes
 
 
 
Chronic Complications 
(S
 
pecific Aim 
 
1) 
 
 
Acute Complications 
(S
 
pecific Aim
 
 
2)
 
 
 
Health-
 
Related Quality of Life 
 
(S
 
pecific Aim 
 
3)
 
 
 
 
Sociocultural 
Factors
 
 
 
 
Race/Ethnicity 
Demographics 
 
Family Structure 
 
Translation:
 
Biology  ?  Clinical   ?  Policy
 

---

Section 4B - Study Objectives/Background and Significance (Phase 3 - 12/2010) 
Section 4B - Page 4 
 Cohort 
Study
 
 
4.2.
 
BACKGROUND AND SIGNIFICANCE 
4.2.1.
 
Goals 
The goal of the SEARCH Cohort Study is to advance substantially knowledge of the 
natural history and determinants of adverse health profiles among racially and ethnically 
diverse youth with T1 or T2 diabetes diagnosed in 2002 - 2008 who had a baseline study 
visit and who have had diabetes for at least 5 years duration.  To accomplish this goal, the 
SEARCH Cohort Study will describe and characterize acute and chronic diabetes-related 
complications and their risk factors, diabetes-related quality of life, mortality, and the 
degree to which barriers to care, quality of care, and transition from pediatric to adult 
care affect diabetes related health outcomes. 
Previous studies have contributed significantly to knowledge regarding the natural history 
of type 1 diabetes in youth.  From 30 years of follow-up in the Pittsburgh Epidemiology 
of Complications (EDC) study of persons diagnosed with T1D in childhood from 1950-
1980, rates of mortality, renal failure, and neuropathy declined significantly with 
diagnosis in more recent eras.  Unfortunately, such favorable trends for complications, 
including coronary artery disease, overt nephropathy and proliferative retinopathy, were 
not observed 
(1)
.  Recent changes in the characteristics of youth with diabetes raise the 
question of whether the previously described patterns of health outcomes continue to 
apply.  Specifically, clinical care for childhood diabetes has evolved, now encompassing 
a number of new types of insulin, delivery systems for insulin, and systems for 
documenting glycemic excursion.  Concurrently, the epidemiology of diabetes has 
evolved.  The incidence rate of T1D has increased around the world 
(2)
 and from 
SEARCH incidence data substantial proportions of adolescent minority youth have T1D 
(for AA adolescents, 42% of incident DM are T1D; 54% for H, 30% for API, and 14% 
for AI) 
(3)
.  Within the last two decades T2D has gone from an infrequent diagnosis, to 
15% of all diagnoses of diabetes in youth 
(4, 5)
.  Finally, as the ethnic diversity of diabetes 
in youth has changed, so also have broader socio-cultural patterns.  For example, 
approximately 50% of AA youth with T1D live in single-parent households and are on 
Medicaid insurance 
(6)
 and similar socio-cultural patterns are observed for other minority 
subgroups and for youth with T2D 
(7 - 10)
.  Because of the importance of these patterns in 
key aspects of diabetes management and control 
(11)
, it is critical to incorporate 
consideration of socio-cultural patterns into the study of the impact of diabetes on health 
outcomes.  
The SEARCH Cohort Study provides a tremendous opportunity to assess prevalence, 
incidence, and correlates of diabetes-related health outcomes by utilizing the well-
established SEARCH study populations and infrastructure.  The SEARCH Cohort Study 
will build on previous work by SEARCH investigative team that has contributed 
substantially to our understanding of the health impacts of diabetes in youth.  In the 

---

Section 4B - Study Objectives/Background and Significance (Phase 3 - 12/2010) 
Section 4B - Page 5 
 Cohort 
Study
 
 
sections below, we provide the key findings from SEARCH in the context of the present 
literature.  Information is presented below regarding health status of youth with diabetes: 
acute complications, chronic complications, risk factors; mortality; and the effects of 
barriers, care quality, and transition to adult care. 
4.2.1.1.
 
Health Status of Youth with Diabetes: Complications and Risk Factors 
4.2.1.1.1.
 
Acute Complications 
The major acute complications of diabetes in youth are diabetic ketoacidosis 
(DKA) and hypoglycemia.  Two European studies reported a frequency of DKA 
of between 21-26% 
(12, 13)
.  In pediatric patients with established diabetes, the 
frequency of DKA ranged from 1-10 per 100 patient years 
(14, 15)
.  Older age, 
higher HbA
1c
, higher insulin doses, mental health diagnoses, and underinsurance 
were associated with higher risk of DKA 
(15)
.  Youth with T2D may also present 
with DKA, with frequencies of 11-25% reported 
(16 – 18)
.  They may also present 
with hyperglycemic hyperosmolar non-ketotic coma (HHNK) 
(19)
.  SEARCH 
reported a similar frequency of DKA at diagnosis of 25.5% 
(20)
. 
Severe hypoglycemia occurs in 10-25% of children with diabetes each year 
(21)
.  
In addition, unrecognized hypoglycemia occurs commonly with up to 73% of 
hypoglycemic episodes occurring without detection by children or their parents 
(22)
. Hypoglycemia unawareness, a condition more common in those with more 
intensive glycemic control, longer duration, and younger age of onset further 
increases the risk of severe hypoglycemia.  Early evidence suggests that use of 
continuous subcutaneous insulin infusions (CSII) paired with continuous glucose 
monitoring (CGM) as a “closed loop artificial pancreas” was associated with a 57-
80% decrease in nocturnal hypoglycemia 
(23)
; however, the impact of new 
technologies on acute complications in diverse populations is not known.  From 
SEARCH, we know that insulin treatment regimens impact the frequency of acute 
complications, with youth on CSII having fewer acute complications, including 
hospitalizations, than youth on other regimens 
(24)
.  SEARCH provides a large, 
multi-ethnic population of youth from diverse economic backgrounds with both 
T1 and T2D to address how acute complications are influenced by both the 
biochemical dimensions of diabetes type, race/ethnicity, other socio-cultural 
factors, and by health care and barriers to care.  Findings will inform 
recommendations for diabetes management and health care delivery to reduce risk 
for acute complications. 

---

Section 4B - Study Objectives/Background and Significance (Phase 3 - 12/2010) 
Section 4B - Page 6 
 Cohort 
Study
 
 
4.2.1.1.2.
 
Chronic Complications