Diabetic Nephropathy

Is autophagy a major contributor to DN and its progression?

Autophagy was discovered in yeast as a stress response and may contribute to the excess of cell death and progression of complications. The human homologues of yeast autophagy genes and drugs known to affect autophagy are available to test the role of autophagy in diabetic nephropathy.

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Diabetic Nephropathy

Can biomarkers predict type 2 diabetic nephropathy

The value of currently available urine biomarkers that identify those at risk for diabetic nephropathy is increasingly called into question. The development of new urine and plasma biomarkers to predict diabetic nephropathy may shed light on disease mechanisms. Also, rational clinical trial design will be made possible by such markers.

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Diabetic Nephropathy

Can we develop "humanized mice" for the study of DN?

While the mouse has many advantages, the human diabetic nephropathy phenotype has been difficult to faithfully replicate in the mouse using candidate gene approaches. Future work should focus on developing "humanized mice," in which loci associated with human diabetic complications are knock-in to the mouse. These animals could then be used to study mechanisms and therapeutics using systems biology approaches.

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Diabetic Nephropathy

A role for the study of non-mammalian model systems in DN?

Non-mammalian model organisms have been underutilized to understand diabetic nephropathy pathogenesis. These simple model organism systems that permit ease of genetic manipulation, rapid throughput and precise measurement of phenotypes. Work published earlier this year (PNAS 107: 775, 2010) demonstrated that type 2 DM risk loci could be characterized in zebrafish. Interestingly, this study demonstrated this study shows ...more »

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Diabetic Nephropathy

Will aggressive treatment of blood sugar slow progression?

Hyperglycemia could cause albuminuria. Should we find out with certainty that either high FBS and/or high 2 hrs PP sugar be treated aggresively before a clinical diagnosis of DM is made

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Diabetic Nephropathy

What is the role of the tubule in early DN?

The primary focus of the pathophysiology of diabetic renal disease has been on the glomerulus. Albuminuria has been shown to be a very sensitive biomarker of proximal tubule injury. Early changes in the proximal tubule may lead to secondary pathology which is typical for diabetic nephropathy. Thus the tubule may represent a therapeutic target for early diabetes.

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Diabetic Nephropathy

Can we restore GBM function in DN?

What are the regulators of glomerular basement membranes? Can we target glomerular endothelium and podocytes to restore normal barrier components and functions?

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Diabetic Nephropathy

Does aldosterone breakthrough occur in DN?

Failure of ACE inhibitors in advanced diabetic nephropathy is an increasing problem. Studies suggest that it is due to aldosterone breakthrough. The mechanism for this escape mechanism is unclear.

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Diabetic Nephropathy

What next after RAAS blockade?

At the current time, we only have RAAS blockade and hypertension control to slow progression to ESRD. What mechanisms should be targeted to slow progression (loss of GFR) in diabetic nephropathy?

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Diabetic Neuropathy

Demyelination

Demyelination is a prominent feature of clinical neuropathy, but absent from rodent models of diabetes (barring occasional reports of fixation artifact). Some markers of Schwann cell fidelity are disrupted, but myelin remains resplendently unchanged in the face of long periods of excess glucose exposure. Do we have to resort to the usual handwaving of "absoute duration of diabetes" being an explanatory factor when the ...more »

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Diabetic Neuropathy

Pipeline fracture

1001 drugs fix NCV slowing in diabetic rodents but none have translated to clinical use. Does NCV slowing in short term rodents have a different pathogenesis to that in humans?

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Diabetic Uropathy

Follow up from Urologic Complications of Diabetes Meeting

Rough drafts of Breakout Group Reports

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