Type 1 diabetes affects more than one million individuals, mostly children and young adults, in the United States and many more worldwide. It occurs in genetically predisposed individuals as a consequence of immune-mediated destruction of the pancreatic islet insulin-secreting beta cells. The present treatment for Type 1 diabetes, when implemented properly, can delay or prevent the long-term complications of diabetes (i.e., blindness, renal failure, and amputation). However, proper diabetes treatment is quite difficult to do, expensive, and very invasive to the diabetic patient's lifestyle. Diabetes is also a major factor in health care costs. Is it possible to prevent Type 1 diabetes or to preserve insulin secretion once diabetes has develped? Several immune interventions have been tried in genetically susceptible individuals without success. Other trials have been attempted to intervene early in the course of Type 1 diabetes, in order to preserve beta cell function. These immune interventions using drugs with potential toxicity have failed. Thus, the identification of agents which either prevent the disease or slow its progression would result in major health care cost savings and reduce complications related to diabetes in addition to the huge individual savings in terms of not having the disease. Our long-term goal is to prevent the development of Type 1 diabetes through the use of innovative based therapies designed to prevent the development of the disease in genetically predisposed individuals. The objectives of this application, in pursuit of that goal and in response to the RFA, is completion of the TrialNet protocols and to continue to develop and test innovative interventions to prevent or slow the progression of Type 1 diabetes. One such innovative approach to slow the progression of Type 1 diabetes is our proposed protocol, """"""""Pioglitazone Preserves Insulin Secretion in Type 1 Diabetes."""""""" The proposed work is innovative because it utilitizes a drug that is in wide spread use with low toxicity yet has immunomodulation and anti- inflamatory properties. We have also designed a series of mechanistic studies to examine whether the anti-inflammatory properties of the drug operate by influencing regulatory T-cells.

Public Health Relevance

The significance of this research is that the prevention of type 1 diabetes will save millions of dollars and enormous human suffering. The identification of agents which either prevent the disease or slow its progression would result in major health care cost savings and reduce complications related to diabetes in addition to the huge individual savings in terms of not having the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK085453-02
Application #
7938971
Study Section
Special Emphasis Panel (ZDK1-GRB-R (O1))
Program Officer
Leschek, Ellen W
Project Start
2009-09-30
Project End
2014-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$662,001
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Ismail, Heba M; Xu, Ping; Libman, Ingrid M et al. (2018) The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes. Diabetologia 61:84-92
Culina, Slobodan; Lalanne, Ana Ines; Afonso, Georgia et al. (2018) Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Sci Immunol 3:
Vecchio, Federica; Lo Buono, Nicola; Stabilini, Angela et al. (2018) Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes. JCI Insight 3:
Redondo, Maria J; Steck, Andrea K; Sosenko, Jay et al. (2018) Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphism and Progression From Single to Multiple Autoantibody Positivity in Individuals at Risk for Type 1 Diabetes. Diabetes Care 41:2480-2486
Sanda, Srinath; Type 1 Diabetes TrialNet Study Group (2018) Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests. Pediatr Diabetes 19:271-276
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk. Diabetes Care 41:1887-1894
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes. Diabetes Care 41:311-317
Sosenko, Jay M; Geyer, Susan; Skyler, Jay S et al. (2018) The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1. Pediatr Diabetes 19:403-409
Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group; Krischer, Jeffrey P; Schatz, Desmond A et al. (2017) Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes: A Randomized Clinical Trial. JAMA 318:1891-1902
Bosi, Emanuele; Boulware, David C; Becker, Dorothy J et al. (2017) Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives. J Clin Endocrinol Metab 102:2881-2886

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