Prevention and treatment of cardiovascular disease remains to be a critical problem in the management of type 1 diabetes (T1D). Since 1999, Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (R01 HL61753) has studied development and progression of coronary atherosclerosis in 654 T1D patients and 766 non-diabetic controls (age 20-55). This cohort has been examined using the electron beam tomography (EBT) and a battery of classical and novel cardiovascular risk factors during the baseline (4/00-3/02) and 3-year follow-up examination (1/03-5/04). Here, we are proposing to investigate mechanisms of cardiovascular complications using stored samples from this large cohort study and to include well-characterized study participants in two substudies utilizing novel techniques to: Disentangle the role of inflammation, immune response and diabetes-related metabolic factors in progression of coronary artery calcification. These processes will be characterized, usingCACTI baseline and 3-year follow-up samples, in 200 subject whose coronary atherosclerosis progressed significantly and 200 control subjects. Prospectively collect peripheral blood samples for measurement of inflammatory (CRP, MMP-9, WBC, MPO, fibrinogen, PAI-1) and immune response factors involved in atherosclerosis, such as SIL-2R, CD40/CD40L, cytokine panel as well as autoantibodies to oxidized LDL. To further our understanding of the role of insulin resistance in accelerated atherosclerosis among T1D patients by studying 48 T1 DM patients and 48 non-diabetic controls using euglycemic hyperinsulinemic clamps. To characterize T1D-specific morphology of coronary plaque and functional corollaries through indepth examination of T1D and non-diabetic subjectes identified with significant plaque burden. Re-analyze jointly already collected prospective data from the CACTI Study the Epidemiology of Diabetes Complications Study (T. Orchard, PI) and the EURODIAB study (J. Fuller, PI), to develop more generalizable estimates of the incidence of clinical CAD in T1D patients, defined by fatal and non-fatal Ml, revascularization or angina, as well as stroke, peripheral artery disease and cause-specific mortality and the incidence and progression rate of subclinical coronary atherosclerosis, characterized by coronary artery calcification.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079611-02
Application #
6950008
Study Section
Special Emphasis Panel (ZHL1-CSR-S (S1))
Program Officer
Rabadan-Diehl, Cristina
Project Start
2004-09-30
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$615,379
Indirect Cost
Name
University of Colorado Denver
Department
Pediatrics
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Millstein, Richard J; Pyle, Laura L; Bergman, Bryan C et al. (2018) Sex-specific differences in insulin resistance in type 1 diabetes: The CACTI cohort. J Diabetes Complications 32:418-423
Bjornstad, Petter; Pyle, Laura; Cherney, David Z I et al. (2018) Plasma biomarkers improve prediction of diabetic kidney disease in adults with type 1 diabetes over a 12-year follow-up: CACTI study. Nephrol Dial Transplant 33:1189-1196
Shah, V N; Sippl, R; Joshee, P et al. (2018) Trabecular bone quality is lower in adults with type 1 diabetes and is negatively associated with insulin resistance. Osteoporos Int 29:733-739
Jensen, Thomas; Bjornstad, Petter; Johnson, Richard J et al. (2018) Copeptin and Estimated Insulin Sensitivity in Adults With and Without Type 1 Diabetes: The CACTI Study. Can J Diabetes :
Bjornstad, Petter; Pyle, Laura; Kinney, Gregory L et al. (2017) Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. J Diabetes Complications 31:369-374
Alman, Amy C; Smith, Steven R; Eckel, Robert H et al. (2017) The ratio of pericardial to subcutaneous adipose tissues is associated with insulin resistance. Obesity (Silver Spring) 25:1284-1291
Bjornstad, P; Costacou, T; Miller, R G et al. (2017) Predictors of early renal function decline in adults with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes and the Pittsburgh Epidemiology of Diabetes Complications studies. Diabet Med 34:1532-1540
Duca, Lindsey M; Maahs, David M; Schauer, Irene E et al. (2016) Development and Validation of a Method to Estimate Insulin Sensitivity in Patients With and Without Type 1 Diabetes. J Clin Endocrinol Metab 101:686-95
Jarvie, Jennifer L; Wang, Hong; Kinney, Gregory L et al. (2016) Lipoprotein-associated phospholipase A2 distribution among lipoproteins differs in type 1 diabetes. J Clin Lipidol 10:577-86
Bjornstad, Petter; Maahs, David M; Jensen, Thomas et al. (2016) Elevated copeptin is associated with atherosclerosis and diabetic kidney disease in adults with type 1 diabetes. J Diabetes Complications 30:1093-6

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