In the initial 1 or 2 years after manifestation of overt type 1 diabetes (referred to as the honeymoon period), exogenous insulin requirements may be minimal because of residual insulin secretion, but eventually the beta cell reserve is exhausted and exogenous insulin becomes essential to control hyperglycemia. Although beta cell destruction is a gradual process, the transition from impaired glucose tolerance to overt diabetes may be abrupt, heralded by an event associated with increased insulin requirements such as infection. The onset of diabetes is marked by polyuria, polydipsia, polyphagia (known as the classic triad of diabetes), and in severe cases, ketoacidosis, all resulting from metabolic derangements (
Fig. 20.24
Since insulin is a major anabolic hormone, its deficiency has widespread effects. The assimilation of glucose into
Islets of Langerhans
Leads to decreased tissue glucose
Fig.20.24Sequenceofmetabolicderangementsleadingtodiabeticcomaintype1diabetesmellitus.Anabsoluteinsulindeficiencyleadstoacatabolicstate,eventuatinginketoacidosisandseverevolumedepletion.Thesederangementsbringaboutsufficientcentralnervoussystemcompromisetocausecomaand,eventually,deathifleftuntreated.Adipose tissue Gluconeogenesis Ketogenesis Muscle Liver Kidney Ketonuria Glycosuria Increased lipolysis (free fatty acids) Increased protein catabolism (amino acids) utilization spillover into blood POLYPHAGIA KETOACIDOSIS HYPERGLYCEMIA POLYURIA DIABETIC COMA VOLUME DEPLETION POLYDIPSIA Glucagon excess d muscle and adipose tissue is sharply diminished or abolished. Storage of glycogen in liver and muscle ceases, and reserves are depleted by glycogenolysis. The resultant hyperglycemia exceeds the renal threshold for reabsorption, and glycosuria ensues. The glycosuria induces osmotic diuresis and polyuria, causing the loss of water and electrolytes. The renal water loss combined with hyperosmolarity due to increased levels of glucose in the blood depletes intracellular water, triggering osmoreceptors in the brain. This sequence of events generates intense thirst (polydipsia). The deficiency of insulin leads to the catabolism of proteins and fats. Gluconeogenic amino acids produced by proteolysis are taken up and by the liver and used as building blocks for glucose. The catabolism of proteins and fats induces a negative energy balance, which in turn leads to increasing appetite (polyphagia), thus completing the classic triad. Despite the increased appetite, catabolic effects dominate, resulting in weight loss and muscle weakness. The combination of polyphagia and weight loss is paradoxical and should always point to the possibility of diabetes.