Insulin-Like Growth Factor Replacement Therapy for Diabetic Neuropathy: Experimental Basis

INTRODUCTION Diabetic neurological complications continue to progress in a substantial fraction of patients despite best efforts at glycemic control. The development of adjuvant treatments to supplement diet, exercise, oral hypoglycemic agents, and insulin is urgently needed and may do much to enhance the quality of patient life. The neurobiology of insulin-like growth factors (IGFs) has been studied in animals, and a loss of IGF activity produces neurological disorders that mimic the disturbances of diabetic neuropathy. The theory that a decline in IGF neurotrophic activity is pathogenic for diabetic neuropathy has efficiently generated many testable hypotheses. The theory predicts and tests show that IGF levels are reduced in diabetic primates, including humans, and that IGF gene expression is reduced throughout the peripheral and central nervous system in diabetic rodents. Tests further show that replacement doses of IGFs can prevent an array of diabetic neurological disturbances in the peripheral and central nervous system. These data point to a common etiology for central and peripheral neurological disturbances. It is of considerable practical and theoretical interest that IGF treatment is effective independently of ongoing hyperglycemia and metabolic imbalance. These observations are in line with emerging clinical data showing that new drugs can be devel-