Diabetic nephropathy (DN) is the leading cause of renal failure, yet pathogenetic understanding remains limited. Objectives of these studies are (a) to develop risk markers based on in vitro studies of cells derived from individual insulin dependent diabetic (IDDM) patients, which are related to renal biopsy endpoints, (b) to ask if these markers represent genetically determined processes and (c) to define relationships between cellular (in vitro) expression of mRNA for extracellular martix (ECM) molecules, their enzymes and enzyme regulators, growth factors, glucose transporters, and sodium/hydrogen antiporter and renal structural and functional endpoints in order to explore basic pathogenic mechanisms in DN; to develop a repository of DNA and cultured cells that will allow evaluation of the cellular functional consequences of genetic variations shown to be linked to DN risk. Three patient groups will be studied: (a) early (~10 years) and long-term (~20 years) IDDM duration patients dichotomized into 2 groups with slow or rapid development of DM lesions, (b) sibling pairs concordant for IDDM, and (c) identical twins discordant for IDDM. DN will be quantitated morphometrically, and factored for duration or expressed as a rate determined by 2 biopsies 5 years apart. The primary endpoint will be mesangial volume fraction [Vv(Mes/glom)] measured by electron microscopic morphometric analysis. Cross-sectional studies of long-term IDDM patients will allow the identification of cellular markers associated with very rapid or very slow development of DN lesions and clinical renal abnormalities. Longitudinal studies (5 year) in shorter-term """"""""fast"""""""" and """"""""slow-track"""""""" patients and IDDM sibling pairs will allow factoring for glycemia and blood pressure and other """"""""environmental variables."""""""" Cultured skin fibroblasts (SF) from individual patients will be evaluated for mRNA expression for the above listed molecules using reverse transcriptase polymerase chain reaction. SF are selected since changes in their phenotype occur in """"""""fast-track"""""""" IDDM patients and are correlated in sibling pairs. These studies will determine the relationship of DN lesions to SF behavior and evaluate whether this behavior is concordant in IDDM sibling pairs who are concordant for DN lesions. SF from nondiabetic identical twins will answer whether hyperglycemia is necessary for the expression of cellular markers of DN risk.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000400-34
Application #
6567470
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2001-12-01
Project End
2002-11-30
Budget Start
Budget End
Support Year
34
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Harbin, Michelle M; Zavala, Hanan; Ryder, Justin R et al. (2018) Associations of sex, age and adiposity in endothelium-independent dilation in children. Physiol Meas 39:045002
Arikawa, Andrea Y; Kaufman, Beth C; Raatz, Susan K et al. (2018) Effects of a parallel-arm randomized controlled weight loss pilot study on biological and psychosocial parameters of overweight and obese breast cancer survivors. Pilot Feasibility Stud 4:17
Foster, Eric D; Bridges, Nancy D; Feurer, Irene D et al. (2018) Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care 41:1001-1008
Ketterl, Tyler G; Chow, Eric J; Leisenring, Wendy M et al. (2018) Adipokines, Inflammation, and Adiposity in Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant 24:622-626
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
Kotlyar, Michael; Thuras, Paul; Hatsukami, Dorothy K et al. (2017) Sex differences in physiological response to the combination of stress and smoking. Int J Psychophysiol 118:27-31
Cole, Abigail J; Kuchnia, Adam J; Beckman, Lauren M et al. (2017) Long-Term Body Composition Changes in Women Following Roux-en-Y Gastric Bypass Surgery. JPEN J Parenter Enteral Nutr 41:583-591
Di Bisceglie, A M; Lombardero, M; Teckman, J et al. (2017) Determination of hepatitis B phenotype using biochemical and serological markers. J Viral Hepat 24:320-329
Beckman, Lauren M; Boullata, Joseph I; Fisher, Paige L et al. (2017) Evaluation of Lean Body Weight Equation by Dual-Energy X-Ray Absorptiometry Measures. JPEN J Parenter Enteral Nutr 41:392-397
Marwaha, A K; Panagiotopoulos, C; Biggs, C M et al. (2017) Pre-diagnostic genotyping identifies T1D subjects with impaired Treg IL-2 signaling and an elevated proportion of FOXP3+IL-17+ cells. Genes Immun 18:15-21

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