++
Diabetes mellitus is a spectrum of common metabolic disorders, arising from a variety of pathogenic mechanisms, all resulting in hyperglycemia. The number of individuals with diabetes is rising rapidly throughout the world. Both genetic and environmental factors contribute to its pathogenesis, which involves insufficient insulin secretion, reduced responsiveness to endogenous or exogenous insulin, increased glucose production, and/or abnormalities in fat and protein metabolism. The resulting hyperglycemia may lead to both acute symptoms and metabolic abnormalities. However, the major sources of the morbidity of diabetes are the chronic complications that arise from prolonged hyperglycemia, including retinopathy, neuropathy, nephropathy, and cardiovascular disease. Fortunately, these chronic complications can be mitigated in many patients by sustained control of the blood glucose. There are now a wide variety of treatment options for hyperglycemia that target different processes involved in glucose regulation or dysregulation.
++
Following a brief review of glucose homeostasis and the pathogenesis of diabetes, this chapter discusses the general approaches and specific agents used in the therapy of diabetes. The last section describes agents used for hypoglycemia.
++
PHYSIOLOGY OF GLUCOSE HOMEOSTASIS
++
Regulation of Blood Glucose. In healthy humans, blood glucose is tightly maintained despite wide fluctuations in glucose consumption, utilization, and production. The maintenance of glucose homeostasis, generally termed glucose tolerance, is a highly developed systemic process involving the integration of several major organs through multilayered communication (Figure 43–1). Although endocrine control of blood glucose, primarily through the actions of insulin, is of central importance, myriad levels of inter-organ communication, via other hormones, nerves, local factors and substrates, also play a vital role. The pancreatic β cell is central in this homeostatic process, adjusting the amount of insulin secreted very precisely to promote glucose uptake after meals and to regulate glucose output from the liver during fasting.
++