Several lines of evidence indicate that Type 2 (non-insulin-dependent) diabetes mellitus is a heterogeneous disease that results from a combination of abnormalities in both insulin secretion and insulin action. The causes of decreased insulin secretion in Type 2 diabetes are still not completely understood, but in a subgroup of Type 2 diabetic patients they may be related to an autoimmune destruction of the pancreatic beta cells. A pronounced activation of the acute-phase response, that was found to be associated with islet cell autoimmunity in the Preliminary Studies, may in part explain the defect in insulin secretion seen in Type 2 diabetes. There have been no extensive investigations, particularly in the U.S., with regard to the prevalence and clinical significance of islet cell autoimmunity particularly in elderly patients with Type 2 diabetes. Two of the most widely used markers for the diagnosis and prediction of autoimmune diabetes, namely GAD65 and IA-2 autoantibodies, along with inflammatory markers of activation of the acute phase response, will be applied in a well-characterized population of Type 2 diabetic patients over the age of 65 from the Cardiovascular Health Study (CHS). The CHS is a longitudinal study, which was proposed to identify and evaluate factors, such as diabetes mellitus, related to the incidence and the natural history of Coronary Heart Disease (CHD) and stroke in non-institutionalized adults 65 years and older. The identification of individuals at risk of developing autoimmune Type 2 diabetes is of public health interest because immunomodulatory strategies could potentially be instituted early enough to prevent the complications related with hyperglycemia and, possibly, the time of onset of insulin requirement. A more appropriate characterization of a subgroup of Type 2 diabetic patients of autoimmune pathogenesis will be of benefit to future research into the etiology, natural history as well as treatment of Type 2 diabetes mellitus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK056200-03
Application #
6635180
Study Section
Special Emphasis Panel (ZRG1-EDC-1 (02))
Program Officer
Staten, Myrlene A
Project Start
2001-04-01
Project End
2005-08-31
Budget Start
2003-04-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2003
Total Cost
$297,846
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Acevedo-Calado, Maria; James, Eddie A; Morran, Michael P et al. (2017) Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development. Diabetes Care 40:561-568
Mitre, Tina M; Pietropaolo, Massimo; Khadra, Anmar (2017) The dual role of autoimmune regulator in maintaining normal expression level of tissue-restricted autoantigen in the thymus: A modeling investigation. Math Biosci 287:12-23
Hecht Baldauff, Natalie; Tfayli, Hala; Dong, Wenxiu et al. (2016) Relationship of adiponectin and leptin with autoimmunity in children with new-onset type 1 diabetes: a pilot study. Pediatr Diabetes 17:249-56
Jaberi-Douraki, Majid; Schnell, Santiago; Pietropaolo, Massimo et al. (2015) Unraveling the contribution of pancreatic beta-cell suicide in autoimmune type 1 diabetes. J Theor Biol 375:77-87
Jaberi-Douraki, Majid; Pietropaolo, Massimo; Khadra, Anmar (2015) Continuum model of T-cell avidity: Understanding autoreactive and regulatory T-cell responses in type 1 diabetes. J Theor Biol 383:93-105
Morran, Michael P; Vonberg, Andrew; Khadra, Anmar et al. (2015) Immunogenetics of type 1 diabetes mellitus. Mol Aspects Med 42:42-60
Michels, Aaron; Zhang, Li; Khadra, Anmar et al. (2015) Prediction and prevention of type 1 diabetes: update on success of prediction and struggles at prevention. Pediatr Diabetes 16:465-84
Jaberi-Douraki, Majid; Liu, Shang Wan Shalon; Pietropaolo, Massimo et al. (2014) Autoimmune responses in T1DM: quantitative methods to understand onset, progression, and prevention of disease. Pediatr Diabetes 15:162-74
Subauste, Angela; Gianani, Roberto; Chang, Annette M et al. (2014) Islet autoimmunity identifies a unique pattern of impaired pancreatic beta-cell function, markedly reduced pancreatic beta cell mass and insulin resistance in clinically diagnosed type 2 diabetes. PLoS One 9:e106537
Fernando, Roshini; Vonberg, Andrew; Atkins, Stephen J et al. (2014) Human fibrocytes express multiple antigens associated with autoimmune endocrine diseases. J Clin Endocrinol Metab 99:E796-803

Showing the most recent 10 out of 32 publications