Abstract

The proposed research will test the following hypotheses: Hypothesis 1: The incidence of IDDM in Allegheny County will continue to rise. Hypothesis 2: There is major geographic variation in the United States and North America by race and ethnic group. Hypothesis 3: There are epidemics of IDDM in our hemisphere and these are associated with the occurrence of chicken pox. Hypothesis 4: High risk HLA DQ heterodimers are independent determinants of diabetes in first degree relatives of probands having IDDM, particularly in the presence of islet cell or GAD antibodies. To evaluate hypotheses 1-3 we will assess the incidence of childhood diabetes in standardized population based registries from Allegheny County, PA plus 17 other directly comparable registries from North America. To test hypothesis 4 we will continue our 15 year follow-up of over 4000 first degree relatives of IDDM cases to examine what precedes overt insulin-dependent diabetes mellitus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK024021-19
Application #
2016010
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Harris, Maureen I
Project Start
1978-09-15
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1998-11-30
Support Year
19
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224

  Publications

Long, Anna E; Wilson, Isabel V; Becker, Dorothy J et al. (2018) Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study. Diabetologia 61:1484-1490
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
Buryk, Melissa A; Dosch, H-Michael; Libman, Ingrid et al. (2015) Neuronal T-cell autoreactivity is amplified in overweight children with new-onset insulin-requiring diabetes. Diabetes Care 38:43-50
Haidet, Jaime; Cifarelli, Vincenza; Trucco, Massimo et al. (2012) C-peptide reduces pro-inflammatory cytokine secretion in LPS-stimulated U937 monocytes in condition of hyperglycemia. Inflamm Res 61:27-35
Bonner, Samantha M; Pietropaolo, Susan L; Fan, Yong et al. (2012) Sequence variation in promoter of Ica1 gene, which encodes protein implicated in type 1 diabetes, causes transcription factor autoimmune regulator (AIRE) to increase its binding and down-regulate expression. J Biol Chem 287:17882-93
Cifarelli, V; Geng, X; Styche, A et al. (2011) C-peptide reduces high-glucose-induced apoptosis of endothelial cells and decreases NAD(P)H-oxidase reactive oxygen species generation in human aortic endothelial cells. Diabetologia 54:2702-12
Morran, Michael P; Casu, Anna; Arena, Vincent C et al. (2010) Humoral autoimmunity against the extracellular domain of the neuroendocrine autoantigen IA-2 heightens the risk of type 1 diabetes. Endocrinology 151:2528-37
Luppi, P; Geng, X; Cifarelli, V et al. (2009) C-peptide is internalised in human endothelial and vascular smooth muscle cells via early endosomes. Diabetologia 52:2218-28
Ma, Xiaosu; Becker, Dorothy; Arena, Vincent C et al. (2009) The effect of age on insulin sensitivity and insulin secretion in first-degree relatives of type 1 diabetic patients: a population analysis. J Clin Endocrinol Metab 94:2446-51
Artz, Evelyn; Warren-Ulanch, Julia; Becker, Dorothy et al. (2008) Seropositivity to celiac antigens in asymptomatic children with type 1 diabetes mellitus: association with weight, height, and bone mineralization. Pediatr Diabetes 9:277-84

Showing the most recent 10 out of 81 publications