Diabetes is an epidemic with profound impacts on quality of life, productivity, and health care costs. Currently there are over 25.8 million Americans with diabetes or pre-diabetes, which works out to approximately 8.3 percent of the population. Statistics also show that the number of diabetes patients is increasing by 5 percent per year and that one in three Americans born in 2000 will likely develop diabetes in his or her lifetime. In just the 10-year period from 1997 to 2007, the annual cost of diabetes in medical expenditures and lost productivity climbed from $98 billion to $174 billion, and the direct medical costs of diabetes almost tripled in that time, from $44 billion to $116 billion (www.diabetes.org).
Diabetes comes in two forms: type 1, which usually begins in childhood and is the result of destruction of critical insulin-secreting cells in the pancreas, and type 2, the form that is rapidly increasing in prevalence as the American population becomes more obese. The destruction of insulin-secreting cells in the pancreas, and severe obesity and the dysregulation of metabolism, cause failure of the body’s glucose regulatory mechanisms. This results in persistent increased blood glucose. Persistent elevated blood glucose that is not properly regulated by insulin damages many tissues, and is associated with the development of debilitating complications that affect the eyes, kidneys, heart, and particularly, the nerves. Almost every person with diabetes will experience at least one of these complications during his or her lifetime.
Despite the high prevalence and the dire need for interventions to assist the growing diabetic population, there are no treatments for diabetic complications and little is known about how and why they occur.
The most common complication of diabetes is nerve damage in the feet, which is initially characterized by intense pain and abnormal sensations of heat, cold, or prickling. This pain is caused by the damaging effects of high blood glucose on peripheral nerves, and is followed over time with numbness and loss of sensation as peripheral nerves die. Pain sensations in the limbs serve to protect the body, and once patients’ nerves die and no longer send signals to the brain, patients become at high risk for undetected limb injuries. These injuries can lead to cutaneous ulcers, infections, tissue death, and lower-limb amputations.
The PNR&D is attacking this huge health problem in many ways. Our scientists are discovering how high blood sugar injures nerves, why this causes pain, and how over time diabetes destroys the nerves. By using animals with diabetes, simulating the insults that nerve cells undergo with diabetes in cultured cells, and studying neuronal changes in patients with diabetic neuropathy, we have discovered some of the key mechanistic pathways involved in neuronal injury during diabetes. These pathways have become the subjects for development of new, groundbreaking therapies.
Current research projects by PNR&D investigators:
- Cutaneous Innervation Center for diabetic neuropathy
- The role of immunity in diabetic peripheral neuropathy
- Cardiac autonomic neuropathy
- SEARCH trial to understand the prevalence of diabetic complications in youth
- Understanding and treating neuropathic pain
- Using neuroimaging techniques to understand and direct new treatments for chronic pain
- Exenatide trial for type 2 diabetic patients with peripheral neuropathy
- Oxidative stress and nervous system injury
- Diabetic nerve loss and triglycerides
- Gene Regulation in Diabetes
- Cellular responses to stress in diabetes
- Working together to understand diabetic complications
- Understanding metabolic responses in complication-prone tissues
- Computational prediction modeling of diabetic neuropathy progression
- Database for diabetes model and patient array data analyses