Diabetes is an epidemic that impacts quality of life, productivity, and health care costs. Currently there are over 30 million Americans with diabetes and 80 million Americans with pre-diabetes. Statistics also show that the number of diabetes patients is increasing by five 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 occurs in adults and is due to tissues no longer being able to respond to insulin, the hormone that lowers blood sugar in the body. Type 2 diabetes is rapidly increasing in prevalence as the USA along with both Europe and Asia experience an epidemic of obesity. In response to obesity, tissues in the body become insulin resistant. Insulin resistance not only results in increases in blood sugar but also increases in blood lipids, especially triglycerides. Persistently elevated blood sugar and lipids damage the eyes, kidneys, heart, and particularly, the brain and nerves. Almost every person with diabetes will experience damage to one or more of these tissues during his or her lifetime, a condition referred to as diabetic complications.
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, known as neuropathy, 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 foot infections, ulcers and lower-limb amputations. A second common complication of diabetes is changes in a person’s ability to think. In fact, there is between a two-to-three-fold higher incidence of Alzheimer’s disease in people with diabetes. Like other tissues in the body, brain cells develop insulin resistance, and this promotes the accumulation of toxic proteins in the brain, including β-amyloid and tau, hallmark features of the brain pathology that characterizes Alzheimer’s disease.
The PNR&D is attacking these important health problem in many ways. Our scientists are discovering how high blood sugar and high lipids injure nerves and nerve cells. By using animals with diabetes, simulating the insults that nerve cells undergo with diabetes in the tissue culture dish, and studying patients with diabetic neuropathy and early problems in thinking (a syndrome called Mild Cognitive Impairment–MCI), we have discovered some of the key mechanisms underlying how the nervous system is damaged during diabetes. These mechanisms provide new drug targets for the development of new, groundbreaking therapies.
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