Showing 2 ideas for tag "diabetic"

Goal 2: Reduce Human Disease

Congential heart defects in diabetic pregnancies: a devastating reality

There is an urgent need to understand the mechanisms underlying diabetes-induced congenital heart defects (CHDs) through basic science research and biomarker identification in human maternal circulation. Majority of the current research in CHDs is related to genetic analyses; however, environmental factors contribute to the majority of human CHDs, but the underlying mechanism is unknown. There is 60 million worldwide... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

More than 32,000 infants are born with heart defects each year in the United States, and about 1 in 150 adults are expected to have some form of congenital heart defect. Approximately, 25% of infants born with heart defects (2.4 per 1,000 live births) require invasive treatment in the first year of life, and in 2009 heart defects were the most common cause of infant death. Therefore, understanding the underlying causes of abnormal heart formation is an essential step towards developing effective new therapeutic treatments or preventions for heart defects. Using diabetes-induced CHDs as research models will reveal critical molecular pathways that contributes to heart cell proliferation and apoptosis.

Feasibility and challenges of addressing this CQ or CC

The same types of heart defects seen in human diabetic pregnancies can be recapitulated in diabetic animal models, making rodents ideal models to investigate how maternal hyperglycemia may induce congenital heart defects. Dietary supplements of natural compounds may be effective against CHDs in diabetic pregnancies. Clinically, new imaging techniques needs be developed for the early diagnosis of CHDs in diabetic pregnancies. Biomarkers in human blood samples needs be detailed analyzed so that we can use small molecules such as microRNA for reliable and early diagnosis.

Name of idea submitter and other team members who worked on this idea Peixin Yang

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Goal 3: Advance Translational Research

New Targets for the Treatment of Heart Failure

Heart failure (HF) is one of the major health challenges in the 21st Century. Its prevalence is due a growing number of patients who survive heart attacks, who later develop heart failure; and the high incidence of diabetes leading to diabetic cardiomyopathy. Current treatments for HF only slow the progression of the disease; no treatment stops or reverses this adverse sequence. These limitations provoke the question... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

The current treatment regimens for patients with heart failure (HF) focus on strategies to reduce cardiac work (by reducing heart rate, beta-blockers), afterload reduction (ACE inhibitors), and decrease in preload/blood volume (ACE inhibitors, aldosterone antagonists, diuretics). None of these treatments stop or reverse the progression of the disease. A recent gene therapy trial designed to improve cardiac contractility and calcium handling in HF has failed in clinical trials. Perhaps the reason that the current and experimental treatments have not produced an outcome of stopping or reversing the progression of the disease relates to the "cell" they are targeting. In this regard, the current treatments principally target cardiac myocytes, but there is evidence that vascular perfusion abnormalities may also be involved in the disease. One such piece of evidence relates to the diffuse fibrosis occurring in the failing hearts. Such fibrosis is often referred to as replacement fibrosis in that the fibrotic tissue has replaced cardiac myocytes which died. This death could be the result of a perfusion abnormalities caused by inadequate dilation of the coronary resistance vessels. Thus, is heart failure a pathology involving both the coronary circulation and cardiac muscle? In this regard, future investigations of heart failure consider cardiac-coronary interactions leading to perfusion abnormalities as a key factor in the progression of heart failure.

Feasibility and challenges of addressing this CQ or CC

The challenge of addressing a coronary vascular contribution to heart failure would involve an interdisciplinary approach using genetic models with cardiac and/or vascular (smooth muscle and endothelium) expression or knock-out of key genes involved in cardiac function and vascular control. Sophisticated measurements of cardiac function and metabolic status of the heart using echocardiography, MRI, PET and a L-Band EPR would provide insight into flow-function-metabolism-oxygenation relations in the normal and failing heart.

Name of idea submitter and other team members who worked on this idea William M Chilian

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