Our understanding of the impact of diabetes on organ function has been evolving since the discovery of insulin in the 1920s. At that time insulin was a miracle drug that appeared to cure diabetes, but over time it became clear that death and disability from diabetes complications involving the eyes, kidneys, peripheral nerves, heart, and vasculature could occur even with treatment. With the improvement in diabetes care over the past 20 years, fewer patients are developing the traditional diabetes complications. However, as people live long and well with the disease, it has become apparent that diabetes can alter function and structure in tissues not typically associated with complications such as the brain and bone. Alteration in brain structure and function are particularly of concern because of the impact of dementia and cognitive dysfunction on overall quality of life.

From large epidemiological studies, it has been demonstrated that both vascular and Alzheimer’s dementia are more common in patients with type 2 diabetes (1). Why this might be true has been difficult to define. Certainly these patients can be expected to have more risk factors such as previous cardiovascular disease, history of hypertension, and dyslipidemia than aged matched control subjects, but when these variables are controlled, the risk for patients with diabetes appears to be higher than that of other subject groups. Persistent hyperglycemia appears to play an important role in cerebral dysfunction. Many years ago, Reaven et al.(2) demonstrated that performance on cognitive tasks assessing learning, reasoning, and complex psychomotor performance was inversely related to glycemic control in a small population of subjects with type 2 diabetes. This issue was recently readdressed in the much larger ACCORD population, where an elevated A1C was found to be linked to reduced performance on neurocognitive tests assessing memory, learning, and executive functions in nearly 3,000 subjects with type 2 diabetes (3). However, the relevance of these observations to younger patients with type 2 diabetes and to patients with type 1 diabetes who may have fewer cardiovascular risk factors is uncertain. Is the dementia and cognitive dysfunction identified in elderly subjects with type 2 diabetes related to their comorbidities and age, or is it the result of a diabetes-related process that begins years earlier? From studies performed in adults with type 1 diabetes, we now know that reductions in measures of motor speed