Diabetes & Obesity I NeuroNetwork
doctor measuring an obese man's waist

Combating the neurologic complications of metabolic dysfunction.

The Problem

Diabetes is a global epidemic and public health burden. Almost 537 million adults are living with diabetes worldwide, a number projected to increase to 784 million by 2045. In the United States, 1 in every 10 adults have diabetes, and over 20% of those don’t even know they have it.  

  • Type 1 diabetes (T1D) can develop at any age but is most frequently diagnosed in adolescents and children. In T1D, the pancreas loses the cells that make insulin, the glucose-regulating biomolecule.  

  • The more common form, type 2 diabetes (T2D), accounts for around 95% of diabetes cases and is most frequently diagnosed in adults. In T2D, the body develops insulin resistance and can no longer regulate glucose. Unfortunately, controlling blood glucose alone is insufficient to slow or reverse damage to complication-prone tissues, including peripheral nerves.  

Obesity and T2D are closely associated, with more than 90% of people with T2D being overweight. Obesity, like T2D, is a growing problem worldwide. According to the CDC, roughly 1 in every 5 children and 1 in every 3 adults in the United States are obese. This is alarming, especially in youth, as obesity often leads to more serious health conditions, such as T2D. Untreated obesity typically worsens with time, first with metabolic syndrome (a cluster of factors that include obesity), then prediabetes, and finally T2D.  

  • Diabetes and obesity negatively impact the peripheral nervous system, which can result in nerve damage in the legs and arms. It can also injure the network of nerves that regulate heart function.  

  • Diabetes and obesity damage both brain structure and function, promoting problems with cognition and thinking.  

Complications of T2D and obesity can eventually lead to significant disability and possibly death. Therefore, our goal is to better understand the complex mechanisms that underlie the relationship between T2D and obesity with nerve and brain health to develop effective treatment and prevention strategies for neurodegeneration and cognitive decline.  

CALCULATE YOUR BMI
Our Key Moments
Our (diabetic) neuropathy program launches
The overarching goal? Determine how diabetes damages nerves to develop novel therapies for diabetic neuropathy.
The feldman lab around 2000 The feldman lab around 2000
Preclinical models
Publish our first report characterizing mouse models of diabetic neuropathy.
Michigan Blue Pantonne Michigan Blue Pantonne
Major funding support
Receive 15-year multi-investigator grant from NIH to assess mechanisms underlying diabetic complications affecting the nerve. (photo shows nerve fibers (green) in a animal model)
nerve fibers shown in green in an image taking from an animal model nerve fibers shown in green in an image taking from an animal model
Metabolism and Alzheimer’s disease
Begin studying the link between impaired metabolism and Alzheimer’s disease in a diabetes mouse model.
Metabolic syndrome induces insulin resistance in both neurons and oligodendrocytes. EVs secreted from these cells are taken up by nearby neurons, which further induces insulin resistance in recipient cells and increases risk of AD. Metabolic syndrome induces insulin resistance in both neurons and oligodendrocytes. EVs secreted from these cells are taken up by nearby neurons, which further induces insulin resistance in recipient cells and increases risk of AD.
Novel technology
Discover genes and related signaling pathways contributing to nerve degeneration in diabetes using advanced bioinformatics techniques.
Gene co-citation network clustered by fast-greedy community structuring algorithm Gene co-citation network clustered by fast-greedy community structuring algorithm
Bioenergetics
Evaluate how bioenergetics (how cells process sugars and fats to make energy) contribute to nerve damage in diabetes.
Fat and neuropathy
Confirm factors other than glucose, such as lipids (fats), contribute to neuropathy in patients with type 2 diabetes.
Neurotransmitters
Show people with diabetes and neuropathy have an imbalance of brain neurotransmitters, molecules that transmit brain signals.
neurotransmitters moving between nerve synapses neurotransmitters moving between nerve synapses
Diabetes and Alzheimer's disease
Demonstrate preclinical mouse models of diabetes develop Alzheimer’s disease pathology in the brain, including changes in tau protein.
tau protein (blue) in neurons (green). tau protein (blue) in neurons (green).
Working together
Form the International Diabetic Neuropathy Consortium with colleagues from Denmark and the United Kingdom to better understand and support neuropathy prevention and treatment.
Insulin resistance in the brain
Show brains from mouse models of diabetes develop insulin resistance (insensitivity to insulin and sugar metabolism), which is linked to tissue pathology in Alzheimer’s disease and protein tau.
people who were part of the International Diabetic Neuropathy Consortium people who were part of the International Diabetic Neuropathy Consortium
Importance of tidying up
Find oxidized cholesterol, which is elevated in diabetes, impairs the function of brain lysosomes (cellular structures that clear debris). If debris is not eliminated, the risk of dementia increases.
Brain stress
Discover obesity in mice induces a process called endoplasmic reticulum stress in brains, a cellular response to stress linked to dementia. (image shows cytoplasm of a neuron)
cytoplasm of a neuron cytoplasm of a neuron
Managing neuropathy
Inform American Diabetes Association guidelines for management of diabetic neuropathy.
American Diabetes Association logo in red and black American Diabetes Association logo in red and black
Obesity as a risk factor
Determine obesity, particularly fat concentrated around the waist, damages peripheral nerves and drives peripheral neuropathy independent of diabetes.
doctor measuring an obese man's waist doctor measuring an obese man's waist
Epigenetics
Identify genes and pathways relevant to diabetic neuropathy are under epigenetic control, a mechanism that regulates gene function without changing DNA sequences.
Obesity and amyloid precursor protein
Demonstrate obesity also impacts pathology of another Alzheimer’s disease protein called amyloid precursor protein, and insulin-like growth factor I prevents this pathology. (photo shows amyloid-beta plaque (red) surrounded by microglia (green) ina. mouse brain)
amyloid_beta_plaque_red_surrounded_by_microglia_green_in_mouse_brain amyloid_beta_plaque_red_surrounded_by_microglia_green_in_mouse_brain
More insight into obesity and neuropathy
Show where fat collects in the body is more important than overall obesity in determining risk of developing neuropathy.
Metabolic risk factors
Report cognitive performance is impaired in severely obese relative to lean controls, and waist circumference (abdominal obesity) is a key metabolic risk factor for cognitive decline.
Diabetes and COVID-19
Establish a Michigan Medicine multidisciplinary clinic for individuals with diabetes and COVID-19 to offer patient care and evaluate factors influencing recovery and long-term complications.
scale tile floor tape measure scale tile floor tape measure
What we eat matters
Demonstrate diets rich in saturated fats (such as red meat) cause increased body weight and poor nerve function. Conversely, diets rich in unsaturated fats (such as olive oil and avocado) do not affect nerve function. We connect these observations to mitochondria (the machinery that generates energy in nerves).
CLARiFY study
With new funding from the NIH, launch CLARiFY Diabetes Complications study in partnership with colleagues in Australia. This clinical study followed persons with type 1 diabetes since the 1990s and enhances our understanding of how diabetes control over 30 years impacts brain structure and function. (image shows brain tractography imaging from this study)
brain tractography showing different nerve tracts in a human brain denoted in different colors brain tractography showing different nerve tracts in a human brain denoted in different colors
Clinical Insights
Discover different lipid species in plasma of people with obesity and type 2 diabetes compared to lean controls.
Flint Neuropathy Study
Launch Flint Neuropathy Study to determine connection between prediabetes, diabetes, obesity, and nerve health in patient cohort from Flint, Michigan. (photo is from this study)
photo of Dr. Melissa Elafros checking a patient for signs of diabetic neuropathy photo of Dr. Melissa Elafros checking a patient for signs of diabetic neuropathy
Research support
Five-year project funded by NIH examines effect of diet and exercise on peripheral nerve function in mouse models of obesity, prediabetes, and diabetes.
Novel technology
Identify alterations in brain microglia due to obesity using advanced single-cell RNA sequencing, a novel sequencing technology that examines changes in gene expression at level of individual cells.
Extracellular vesicles
Propose extracellular vesicles may be missing link between metabolic dysregulation and Alzheimer’s disease due to their ability to propagate Alzheimer’s disease pathology and insulin resistance. (image shows extracellular vesicles (red) surrounding a nucleus (blue))
Ongoing efforts
Focus on how inflammation due to aging, diabetes, and metabolic dysfunction (such as obesity) impacts nerve health in the brain and how metabolic control over time can predict diabetic complication risk and inform intervention opportunities.
extracellular vesicles surrounding a nucleus extracellular vesicles surrounding a nucleus
Neurologic Complications
Brain Health
Neuropathy
Diabetes & Obesity Initiatives
Lifestyle Interventions

Growing evidence indicates that changes in diet and exercise can prevent diabetic neuropathy and improve brain health.

Mental Health

Investigating how diabetes affects mental health.

CLARiFY Study

Investigating lifelong factors that influence brain health in individuals with Type 1 diabetes, followed for 30 years from childhood diagnosis.

Flint Neuropathy Study

Understanding the extent of undiagnosed diabetes and neuropathy among primary care patients in Flint, Michigan.