Microsoft Word search phase 3 Title Page Amendment

Diabetic Nephropathy.  The incidence of diabetic end-stage kidney disease 
(ESKD) in 2007 was more than double that in 1990 
(46)
, with even greater 
increases among AA and AI populations.  Worsening glomerular filtration rate 
(GFR) carries up to a three-fold risk of cardiovascular event and six-fold risk of 
death 
(47)
.  Correlates of diabetic kidney disease include glycemic control 
(48, 49)
, 
diabetic retinopathy 
(50)
, blood pressure 
(51, 52)
 and possibly lipids 
(53, 54)
, 
inflammatory and fibrotic markers 
(55 - 57)
, vitamin D deficiency 
(58, 59)
 and 
diagnosis during puberty 
(60 - 65)
; and in T2D, nephropathy has been associated 
with increased pulse wave velocity 
(66, 67)
.  From SEARCH, the prevalence of 
elevated urinary albumin-to-creatinine ratio (ACR) was 9.2% in youth with type 1 
and 22.2% in type 2 diabetes (p< 0.0001).  In multiple logistic regression analysis, 
female sex, higher A1C and triglyceride values, hypertension, and type of 
diabetes (T2 versus T1D) were significantly associated with elevated ACR.  
Adjustment for variables related to insulin resistance (obesity, hypertension, 
dyslipidemia, and inflammation) attenuated, but did not completely explain, the 
association of diabetes type with elevated ACR 
(68)
.  The SEARCH Cohort Study 
will provide much needed additional information in a longitudinal design.  
SEARCH is uniquely positioned to obtain critical information regarding the 
prevalence and risk factors of diabetic nephropathy across subgroups of diabetes 

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Section 4B - Study Objectives/Background and Significance (Phase 3 - 12/2010) 
Section 4B - Page 8 
 Cohort 
Study
 
 
type and race/ethnicity.  Especially important, since so little is known, SEARCH 
will provide much needed information on early nephropathy in T2D.  
Neuropathy.  The topic of diabetic neuropathies is complex both due to the 
diverse clinical manifestations and due to difficulties in measurement methods.  
Here we focus on chronic distal symmetric polyneuropathy (i.e., peripheral 
neuropathy) and cardiac autonomic neuropathy. 
Peripheral neuropathy may occur in at least 20% of adults with diabetes, and risk 
increases with glycemia, dyslipidemia, hypertension, diabetes duration, height and 
possibly with cigarette smoking and alcohol consumption 
(61, 69 - 71)
.  There is 
limited information available on the prevalence and determinants of peripheral 
neuropathy among youth with diabetes, and studies are quite difficult to interpret 
due to substantial differences in measurement methods.  Eppens et al 
(40)
 reported 
1,433 T1DM youth with onset < 18 years of age, compared with 68 T2D subjects 
from Australia, with a median duration of 6.8 years (T1D) and 1.3 years (T2D).  
There was no difference between T2D and T1D in the prevalence of peripheral 
neuropathy (21% vs. 27%).