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Radiographic and proteomic characterization of bone health in patients with type 2 diabetes and type 1 diabetes of extreme duration
Summary Data Summary
Applicant Keenan, Hillary
E-Mail Address hillary.keenan@joslin.harvard.edu
Project Title Radiographic and proteomic characterization of bone health in patients with type
2 diabetes and type 1 diabetes of extreme duration
CBU ID 15GHSU2509
External SubContract ID 25034-62
Diabetic Complication All Complications
Funding Program Group Pilot & Feasibility [PF2015]
Abstract Decreased bone health and subsequent fracture is one of the less considered
complications of both type 1 (T1DM) and type 2 (T2DM) diabetes, but has
significant impact on quality of life and mortality. Studies have shown that in
30% of hip fracture cases, death occurs within one year of the event. This is of
significant concern, with fracture rates increasing among both those with T1DM
and T2DM due to the aging population. Individuals with T1DM are most at risk
with up to a 12-fold increased risk of hip, wrist or vertebral fractures.
Studies on the structural defects resulting from T2DM cite not only the toxic
effects of hyperglycemia but also hyperinsulinemia, implicated in osteoblast
proliferation. In addition, excess adiposity characteristic of T2DM contributes
to increased levels of adipokines, such as leptin, which inhibit osteoclast
formation, unbalancing bone formation and resorption. The culmination of these
T2DM characteristics are hypothesized to lead to overall decreased bone
turnover, increasing bone mineral density, yet there is greater cortical
porosity and poorer bone quality, increasing fracture risk. Much less is
understood regarding the structural and biochemical profile of bone pathology in
T1DM, where resorption appears to be at the crux of the imbalance. Little is
understood regarding how the pathways of hyperglycemic toxicity, the differing
phenotypes of T1DM and T2DM, and aging related factors affect bone health. The
Joslin 50-Year Medalist Study has extensively characterized a cohort (n=1,000)
with over 50 years of T1DM, with mean duration of 55 years and age of 69 years.
In preliminary data from dual energy X-ray absorptiometry (DEXA) scans of 65
Medalists, the prevalence of osteoporosis (T-score < -2.5SD) was only 4.6%
across sites including lumbar spine, total hip and femoral neck, while the
prevalence of osteopenia (T-score < -1.0SD) was 70.8%. Diabetes duration, age at
onset and glycemic control did not differ for osteoporosis or osteopenia. Among
four female Medalists who received high resolution peripheral computed
tomography (HR-pQCT), differences from normative data were not only in the
cortical but also in the trabecular aspects of the distal radius and tibia. This
contrasts literature reports of T2DM post-menopausal women showing increases in
radial cortical porosity, but no defects in other bone morphology. These
hypotheses as to mechanisms and early data regarding morphologic changes suggest
further work is needed to characterize the differences of type 1 and type 2
diabetic osteoporosis to identify possible therapies and interventions. To do
this we propose to 1.) Characterize bone health by DEXA and HR-pQCT in those
with extreme duration type 1 diabetes (Medalists); 2.) Characterize bone health
by DEXA and HR-pQCT in a matched group of individuals with type 2 diabetes and
nondiabetic controls, and compare to those with extreme duration type 1
diabetes; 3.) Characterize and compare the plasma protein profiles associated
with morphologic features of type 1 diabetes, type 2 diabetes and non-diabetic
controls.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 20768
Supply Total Costs 43934
Equipment Total Costs 0
Travel/Other Total Costs 22571
Direct Costs 87273
Indirect Costs Proposed 12727
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 10/1/2015
End Date 9/30/2016
IFO Name O'Brien, Joseph
IFO E-Mail Address joe.o'brien@joslin.harvard.edu
IACUC/IRB No. 2013-13
IACUC/IRB Institution Joslin Diabetes Center - Boston
Entity ID No. 04-2203836
Report Request Date 10/30/2016
T1D NO
TypeCount
Invoices 2
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  15GHSU250925034-62Joslin Diabetes Center - Boston8/12/2016$11,974.46$1,549.42$13,523.88$150.29View PDF
  View  15GHSU250925034-62Joslin Diabetes Center - Boston10/28/2016$75,148.80$11,177.03$86,325.83$150.29View PDF


Reports
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