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University of Alabama at Birmingham
Cellular Bioenergetics as a Predictor of Diabetic Nephropathy
The pathophysiology of diabetes is associated with a spectrum of complications including renal disease that currently affects about 30% of diabetics. Diabetic nephropathy is usually characterized by variable degrees of albuminuria and a progressive deterioration in glomerular filtration rate (GFR). Importantly, diabetic nephropathy is the leading cause of end stage renal disease in the US accounting for about 45% of all cases. At the present time no clinical test is available to predict which patients will progress rapidly. If such a test were available, it would greatly aid in management allowing more effective timing of dialysis and transplant and so improve therapeutic outcome and quality of life. Since diabetes is a systemic disease associated with severe bioenergetic dysfunction in a broad range of tissues, we hypothesized that those patients with severe cellular bioenergetic defects detectable in circulating platelets, lymphocytes and monocytes will progress more rapidly to end stage renal disease. Although the concept that circulating blood cells can serve as a biomarker for the severity of diabetes has been recognized previously it has not been exploited for patient management. A major breakthrough in this area has been the development of novel methods to assess cellular bioenergetics in peripheral blood mononuclear cells and platelets using only 20ml of blood. Importantly, we have shown that mitochondrial function is quite different in different cell types necessitating an independent evaluation of the potential to predict severity of renal disease in diabetic patients. This translational pilot proposal builds on these findings with a collaborative project between clinicians with expertise in the management of diabetic patients with renal disease and basic researchers who are expert in cellular bioenergetics at UAB. In this proposal we will test this concept using an adaptive study design to determine whether the severity of bioenergetic dysfunction is a predictor of the rate of progression of renal disease. The project will serve the diabetic community by introducing a novel biomarker for the progression of diabetic nephropathy and serve as the basis for the possible future development of novel bioenergetic based therapeutics.
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Cellular Bioenergetics as a Predictor of Diabetic Nephropathy (Darley-Usmar, Victor)
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Year: 2014; Items: 3
A review of the mitochondrial and glycolytic metabolism in human platelets and leukocytes: Implications for their use as bioenergetic biomarkers.
Kramer PA, Ravi S, Chacko B, Johnson MS, Darley-Usmar VM
, 2014 (2), 206 - 210
Mitochondria in monocytes and macrophages-implications for translational and basic research.
Ravi S, Mitchell T, Kramer PA, Chacko B, Darley-Usmar VM
The international journal of biochemistry & cell biology
, 2014 (53), 202 - 207
The Bioenergetic Health Index: a new concept in mitochondrial translational research.
Chacko BK, Kramer PA, Ravi S, Benavides GA, Mitchell T, Dranka BP, Ferrick D, Singal AK, Ballinger SW, Bailey SM, Hardy RW, Zhang J, Zhi D, Darley-Usmar VM
Clinical science (London, England : 1979)
, 2014 (127), 367 - 373
Year: 2013; Items: 1
Methods for defining distinct bioenergetic profiles in platelets, lymphocytes, monocytes, and neutrophils, and the oxidative burst from human blood.
Chacko BK, Kramer PA, Ravi S, Johnson MS, Hardy RW, Ballinger SW, Darley-Usmar VM
Laboratory investigation; a journal of technical methods and pathology
, 2013 (93), 690 - 700
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The DiaComp Steering Committee is the governing body of the consortium. The principle function of this committee is to guide the scientific direction of the consortium. This is accomplished by creating various subcommittees necessary to advance the scientific goals and providing guidance to the broader complications research community. Policies for the consortium are developed through consultation with the
External Evaluation Committee
The DiaComp Nephropathy Committee has the principal function of furthering the mission of the consortium with regard to diabetic kidney disease.
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Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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