The Diabetes Control and Vascular Disease study seeks to determine the natural history of juvenile diabetes and the relation of diabetic glycemia and other determinants to the development of microvascular and macrovascular disease in a large homogeneous group of Type I diabetic patients. It is proposed to continue observations of this well-defined cohort to further characterize occurrences of diabetic complications in relation to their determinants.
Our aims are to: 1) delineate and define the evolution of small vessel disease in the retina of these young- adult diabetics by serial ophthalmological examinations (clinical, fluorescein angiography, fundus photography, retinal blood flow measurement by the laser Doppler technique), 2) further refine our recently developed index of the rate of progression of early diabetic retinopathy and develop other empirical methods for hierarchical scoring of other phases of diabetic retinopathy, 3) relate the severity thus measured and its components to the characteristics of the patient and the disease (e.g. level of glycemia, muscle CBMT, hormonal, genetic factors), 4) explore the role of the genome in susceptibility to diabetes and its complications by examining, separately and jointly, the relation of extended major histocompatibility (MHC) haplotypes (chr. 6), haplotypes defined by restriction fragment length polymorphisms (RFLPs) of large DNA regions on the short arm of chr. 11, and RFLPs for human IGF-I, IGF-II and aldehyde reductases, and 5) complete the typing and establishment of permanent lymphoblastoid cell lines from every study participant and selected families.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK039044-04
Application #
3238698
Study Section
(SSS)
Project Start
1987-08-01
Project End
1991-07-31
Budget Start
1988-08-10
Budget End
1989-07-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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Owerbach, D; Gabbay, K H (1994) Linkage of the VNTR/insulin-gene and type I diabetes mellitus: increased gene sharing in affected sibling pairs. Am J Hum Genet 54:909-12
Harrison, D H; Bohren, K M; Ringe, D et al. (1994) An anion binding site in human aldose reductase: mechanistic implications for the binding of citrate, cacodylate, and glucose 6-phosphate. Biochemistry 33:2011-20
Bohren, K M; Grimshaw, C E; Lai, C J et al. (1994) Tyrosine-48 is the proton donor and histidine-110 directs substrate stereochemical selectivity in the reduction reaction of human aldose reductase: enzyme kinetics and crystal structure of the Y48H mutant enzyme. Biochemistry 33:2021-32
Wang, K; Bohren, K M; Gabbay, K H (1993) Characterization of the human aldose reductase gene promoter. J Biol Chem 268:16052-8
Bohren, K M; Gabbay, K H (1993) Cys298 is responsible for reversible thiol-induced variation in aldose reductase activity. Adv Exp Med Biol 328:267-77
Wilson, D K; Bohren, K M; Gabbay, K H et al. (1992) An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science 257:81-4
Bohren, K M; Grimshaw, C E; Gabbay, K H (1992) Catalytic effectiveness of human aldose reductase. Critical role of C-terminal domain. J Biol Chem 267:20965-70
Bohren, K M; Page, J L; Shankar, R et al. (1991) Expression of human aldose and aldehyde reductases. Site-directed mutagenesis of a critical lysine 262. J Biol Chem 266:24031-7
Owerbach, D; Gunn, S; Gabbay, K H (1990) Multigenic basis for type I diabetes. Association of HRAS1 polymorphism with HLA-DR3, DQw2/DR4, DQw8. Diabetes 39:1504-9

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