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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Hemoglobin A1c (HbA1c), a long-term, integrated average of tissue exposure to hyperglycemia, is the best reflection of average glucose concentrations and the best proven predictor of microvascular complications of diabetes mellitus. However, HbA1c fails to capture glycemic variability and the risks associated with extremes of hypoglycemia and hyperglycemia. These risks are the primary barrier to achieving the level of average glucose control that will minimize both the microvascular and the long-term macrovascular complications of type 1 diabetes. High blood glucose levels largely due to prandial excursions produce oxidative and inflammatory stress with potential acceleration of preexisting atherosclerosis and increased cardiovascular risk. Moreover, some temporal aspects of glycemic variation, including the rates of rise and fall of glucose, are associated with adverse cognitive and mood symptoms in those with diabetes. Methods to quantify the risk of glycemic extremes, both high and low, and the variability including its temporal aspects are now more precise than ever. These important endpoints should be included for use in clinical trials as useful metrics and recognized by regulatory agencies, which has not been the case in the past. Precise evaluation of glycemic variability and its attendant risks are essential in the design of optimal therapies; for these reasons, inclusion of these metrics and the pulsatile hormone patterns in mathematical models may be essential. For the clinician, the incursion of mathematical models that simulate normal and pathophysiological mechanisms of glycemic control is a reality and should be also gradually incorporated into clinical practice., (© Diabetes Technology Society)

The brain uses glucose as its primary fuel. Cerebral metabolism of glucose requires transport through the blood-brain barrier, glycolytic conversion to pyruvate, metabolism via the tricarboxylic acid cycle and ultimately oxidation to carbon dioxide and water for full provision of adenosine triphosphate (ATP) and its high-energy equivalents. When deprived of glucose, the brain becomes dysfunctional or can be even permanently damaged. Glucose is stored as glycogen within astrocytes with potential importance for tolerance of hypoglycemia. Glycogen may also be important for the metabolic response to somatosensory stimulation and coupling of blood flow and cellular metabolism. Uncontrolled diabetes has a variety of adverse effects upon brain metabolism and function. Many aspects of function that affect the brain may be indirectly linked to cerebral glucose metabolism. Neurotransmitter metabolism, cerebral blood flow, blood-brain barrier and microvascular function may all be affected to varying degrees by either hypoglycemia or uncontrolled diabetes mellitus.

The brain is not usually thought to be a target of chronic diabetes complications. Nonetheless, substantial evidence, summarized herein, suggests that diabetes causes brain damage. Clinical syndromes of diabetes-related brain abnormalities are discussed along with possible causes. Various physiological effects of diabetes are reviewed, and questions are raised about gaps in our knowledge. Appropriate directions for future research are suggested.

Home monitoring of capillary blood glucose concentrations has changed diabetes care, giving physicians and patients a way to adjust their therapy and achieve better diabetic control. The practical strategies and equipment for home diabetic monitoring are discussed, including the changing role of urine testing and how inexpensive machines may enhance the value of blood glucose monitoring.

Home monitoring of capillary blood glucose concentrations has changed diabetes care, giving physicians and patients a way to adjust their therapy and achieve better diabetic control. The practical strategies and equipment for home diabetic monitoring are discussed, including the changing role of urine testing and how inexpensive machines may enhance the value of blood glucose monitoring.

The effect of diabetes on the metabolism of glucose and lactate was examined in isolated rat cerebral microvessels. In rats with diabetes induced with streptozotocin, glucose oxidation to CO2 by the microvessels was decreased by 54-83% and its conversion to lactate by 21-61%. Insulin therapy for several days or starvation for 48 h both lowered blood glucose levels in the diabetic rats and restored microvessel glucose metabolism to normal. Cerebral microvessels consist principally of the capillaries that constitute the blood-brain barrier. Direct assessment of the blood-brain barrier in vivo using the brain uptake index (BUI) technique revealed a close parallel to the findings in the microvessels. Thus, hexose transport was diminished in diabetic rats and restored to normal by both insulin therapy and starvation. The oxidation of [1-14C]lactate to CO2 like that of glucose was depressed in microvessels of diabetic rats. In contrast to glucose, however, the transport of lactate across the blood-brain barrier in vivo was not altered. These findings suggest that diabetes suppresses glucose metabolism in rat cerebral microvessels and downregulates glucose transport across the blood-brain barrier. They also suggest that both of these processes are regulated by chronic alterations in blood glucose concentration rather than by insulin per se.