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Gene X Environment Interaction in Diabetic Nephropathy: The Look AHEAD Trial
Summary Data Summary
Applicant McCaffery, Jeanne
E-Mail Address jeanne_mccaffery@brown.edu
Project Title Gene X Environment Interaction in Diabetic Nephropathy: The Look AHEAD Trial
CBU ID 13GHSU266
External SubContract ID 25034-34
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2013]
Abstract This grant application responds to the Diabetic Complications Consortium’s
Annual Pilot and Feasibility Program, addressing the three following areas of
interest: 1) testing the role of genes of loci that arise from ongoing human
genetics efforts, 2) use of relevant model systems to accelerate gene x
environment studies and 3) analysis of human data and cohorts to elucidate
epidemiologic/population associations relative to understanding diabetic
complications.
Roughly 40% of individuals with diabetes experience diabetic nephropathy (DN),
substantially increasing risk for end-stage kidney disease, cardiovascular
disease events and mortality. Behavioral intervention targeting weight and
physical activity appears to be an environmental/behavioral intervention
successful in reducing incidence of chronic kidney disease (CKD) in overweight
individuals with type 2 diabetes. At the same time, genome-wide association
studies (GWAS) have been successful in discovering genetic markers associated
with chronic kidney disease (CKD) in the general population and DN in type 1
diabetes. The prognostic value of these genetic markers for DN among individuals
with type 2 diabetes and the potential for gene x environment interaction
involving weight loss, diet and physical activity remains unclear. This pilot
and feasibility study will enable us to begin to determine whether human genetic
discoveries in kidney disease predict the course of diabetic nephropathy among
overweight or obese individuals with type 2 diabetes. Using gene x environment
interaction models, we will also determine whether randomized lifestyle change
involving weight loss through calorie restriction and physical activity can
diminish these effects.
The Look AHEAD (Action for Health and Diabetes) Study is an NIH-funded,
multi-center randomized controlled trial with the primary goal of determining
the health benefits of weight loss achieved through an intensive lifestyle
intervention (ILI), including diet and physical activity, relative to Diabetes
Support and Education (DSE) among overweight or obese individuals with type 2
diabetes (N = 4,045 with genetic consent and successful genotyping). Given the
successful weight loss and associated reduction in DN over 10 years follow-up,
Look AHEAD provides a unique opportunity to determine the prognostic value of
single nucleotide polymorphisms (SNPs) associated with CKD in DN and whether
weight loss and physical activity can blunt these associations. Support for this
work will provide pilot data for a larger application seeking additional
genotyping to determine common and distinct SNPs associated with incidence of
nephropathy, retinopathy and neuropathy over ten years in this overweight,
diabetic cohort and whether these genetic associations are mitigated through
environmental intervention (GxE).
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 42822
Supply Total Costs 0
Equipment Total Costs 0
Travel/Other Total Costs 2000
Direct Costs 44822
Indirect Costs Proposed 20618
Total Costs Proposed 65440
Total Costs Approved 65440
Start Date 10/1/2013
End Date 9/30/2014
IFO Name Gillespie, Susie
IFO E-Mail Address ora@lifespan.org
IACUC/IRB No. 9999
IACUC/IRB Institution The Miriam Hospital
Entity ID No. 1050258905A1
Report Request Date 10/30/2014
T1D NO
TypeCount
Invoices 11
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  13GHSU26625034-34The Miriam Hospital9/18/2014$6,433.21-$6,433.21-View PDF
  View  13GHSU26625034-34The Miriam Hospital8/14/2014$2,537.31-$2,537.31-View PDF
  View  13GHSU26625034-34The Miriam Hospital7/15/2014$2,356.08-$2,356.08-View PDF
  View  13GHSU26625034-34The Miriam Hospital6/16/2014$3,238.44-$3,238.44-View PDF
  View  13GHSU26625034-34The Miriam Hospital5/14/2014$3,094.80-$3,094.80-View PDF
  View  13GHSU26625034-34The Miriam Hospital4/15/2014$3,268.70-$3,268.70- 
  View  13GHSU26625034-34The Miriam Hospital3/14/2014$1,153.63$530.67$1,684.30-View PDF
  View  13GHSU26625034-34The Miriam Hospital2/13/2014$1,173.65$539.88$1,713.53-View PDF
  View  13GHSU26625034-34The Miriam Hospital10/15/2014$12,449.50-$12,449.50-View PDF
  View  13GHSU26625034-34The Miriam Hospital1/20/2014$1,153.62$530.67$1,684.29-View PDF
  View  13GHSU26625034-34The Miriam Hospital1/15/2015$26,979.84-$26,979.84-View PDF
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