Diabetes Grants

Role of NADPH Oxidase 5 (NOX5) in Diabetic Neuropathy

Dr. Eva Feldman was awarded an NIH grant (U24DK115255) as part of DiaComp to study oxidative stress in neuropathy. The goal is to gain a better understanding of NOX5-derived free radicals to support our efforts to develop and validate novel therapies that prevent nerve damage in diabetes, prediabetes, and obesity.

Prediabetic, diabetic, and obese  individuals frequently develop neuropathy, i.e., nerve damage, but the mechanisms are not fully understood. Moreover, there are no treatments available to prevent or slow the progression of neuropathy. Oxidative stress, the presence of damaging “free radicals”, is one potential route of nerve damage. This grant will examine the contribution of an enzyme called NOX5 to free radicals in neuropathy, which could serve as a potential drug target.

Linking Nerve Bioenergetics with Metabolomics: New Insights into Diabetic Neuropathy

Dr. Eva Feldman received this NIH grant (R21NS102924) to investigate the link between energy production and neuropathy in prediabetes and diabetes . The major goal of this project is to identify bioenergetics—how cells transform energy—pathways whose regulation play crucial roles in the pathogenesis of diabetic peripheral neuropathy.

Mitochondria are cellular structures that generate the energy needed for keep cells and organisms alive and may be defective during the development of neuropathy. This study will study how mitochondria fail in neuropathy and also if this is linked to the presence or absence of certain metabolites.

Michigan Mouse Metabolic Phenotyping Center

Dr. Feldman’s research uses mouse models of diabetes to understand the mechanisms that lead to neuropathy. This NIH grant (U2CDK110768) was awarded to measure prediabetes- and diabetes-induced nerve, eye, and kidney damage in mice. The ultimate goal of this project is to phenotype murine models for neuropathy.

Integrated Systems Biology Approach to Diabetic Microvascular Complications

Dr. Eva Feldman was awarded this NIH grant (R24DK082841) to investigate microvascular complications in diabetes.

Microvascular complications refer to the gradual damage to nerve, eye, and kidney tissues during diabetes. Controlling blood glucose does not always prevent these from occurring, so Dr. Feldman and her team are investigating the effect of abnormal lipid (fats) profiles. They will look at tissue-specific effects of lipids in nerve, eye, and kidney and will will seek to identify lipid “signatures”, i.e., the presence or absence of specific lipids, that are linked to tissue-specific complications. It will also seek to identify potential lipids that could be possible treatment targets.

Targeting Inflammation and Salsalate as a Novel Therapy for Diabetic Neuropathy

 

 

Dr. Eva Feldman jointly received this NIH grant with Dr. Rodica Pop-Busui (R01DK107956) to run a clinical trial in type 1 diabetes patients. They are testing the effectiveness of a compound called salsalate on the progression of neuropathy.

SEARCH for Diabetes in Youth Cohort Study

Dr. Eva Feldman was awarded this CDC & NIDDK grant (R01DK108173) as a member of a larger study called “SEARCH for Diabetes in Youth Cohort Study”. This clinical study is being performed to assess the occurrence of neuropathy in young individuals with type 1 and type 2 diabetes  to monitor the onset of diabetic autonomic and peripheral neuropathy in children.

The International Diabetic Neuropathy Consortium (IDNC)

This grant was awarded by the Novo Nordisk Foundation to Dr. Eva Feldman. The study will look at the presence and absence of certain metabolites in the blood of both mouse models and humans with type 2 diabetes. The goal is to search for specific patterns of metabolites, or “signature”, of diabetes and to identify targets to develop treatments.

The Effect of High Intensity Interval Training and Surgical Weight Loss on Distal Symmetric Polyneuropathy Outcomes

Dr. Callaghan won this grant from the National Institutes of Health (R01DK115687) to evaluate approaches for preventing diabetic neuropathy. The study will test two approaches. First, participants will be divided into two groups, one that undergoes bariatric surgery (weight-loss surgery) and one that does not. Second, participants from each group (surgery and no surgery) will be divided randomly into high intensity exercise or regular exercise. Patients will be evaluated for neuropathy to determine the most effective approach(es). This study is registered at ClinicalTrials.gov (NCT03617185).

Sphingolipid and Fatty Acid Biology in Prediabetes and Neuropathy

Dr. Rumora was awarded a grant from the National Institutes of Health (K99DK119366) to investigate a dietary method for preventing diabetes induced neuropathy. The goal is to identify monosaturated fat (MUFA) supplementation as an accessible and targeted therapy to reverse toxic ceramide accumulation and reverse or halt the progression of neuropathy. In this study, Dr. Rumora will determine whether a diet enriched in monounsaturated fatty acids, such as present in olive oil and other oils, instead of saturated fatty acids, such as found in butter, can prevent the development or severity diabetic neuropathy. She will also be investigating the link of a type of lipid called ceramides with diabetic neuropathy.