The exocrine functions of the pancreas involve the synthesis and release of digestive enzymes and sodium bicarbonate from specialized cells of the pancreas called acini cells. The acini cells release their contents into the pancreatic duct. From the pancreatic duct, the enzymes and bicarbonate solution travel through the sphincter of Oddi into the first section of the small intestine, the duodenum. The pancreatic enzymes and bicarbonate solution both play important roles in the digestion and absorption of food in the small intestine.

The endocrine functions of the pancreas involve the synthesis and release of the hormones insulin, glucagon, and somatostatin. These hormones are each produced by separate, specialized cells of the pancreas, called the islets of Langerhans.

Hypoglycemia occurs when the blood glucose level falls below 50 mg/100 mL of blood. Hypoglycemia is caused by an imbalance between glucose production and utilization. It can be caused by fasting or, especially, fasting coupled with exercise, because exercise increases the usage of glucose by skeletal muscle. Most commonly, hypoglycemia is caused by an insulin overdose in an insulin-dependent diabetic.

The brain relies on glucose as its main energy source and because it cannot synthesize or store glucose, it is dependent on circulating blood glucose to maintain normal functioning. Hypoglycemia results in many symptoms of altered central nervous system (CNS) functioning, including confusion, irritability, seizure, and coma. Hypoglycemia can cause headache, as a result of alteration of cerebral blood flow, and changes in water balance. Systemically, hypoglycemia causes activation of the sympathetic nervous system, stimulating hunger, nervousness, sweating, and tachycardia. Anxiety levels increase due to the diabetic being shaky and agitated.

Hyperglycemia is defined as a condition when plasma glucose level is higher than the normal (fasting range of 126 mg/100 mL of blood). Hyperglycemia is usually caused by insulin deficiency, as seen in type 1 diabetes, or as a result of decreased cellular responsiveness to insulin, as seen in type 2 diabetes (the types of diabetes are discussed in the following section). Hypercortisolemia, which occurs in Cushing syndrome and in response to chronic stress, can cause hyperglycemia by the stimulation of liver gluconeogenesis. Acute conditions of elevated thyroid hormone, prolactin, and growth hormone all increase blood glucose as well. Prolonged high levels of these hormones, especially growth hormone, are considered diabetogenic (producing diabetes) because they overstimulate insulin release by beta cells of the pancreas, leading to an eventual decrease in the cellular response to insulin. Sympathetic nervous stimulation and epinephrine released from the adrenal gland also raise plasma glucose levels, especially during periods of stress. The catecholamines epinephrine and norepinephrine inhibit insulin secretion, increase the breakdown of stored fats, and promote the use of glycogen for energy. By these mechanisms, the catecholamines make a variety of alternative energy sources available for the body to use instead of glucose, thereby raising plasma glucose levels and increasing its availability for use by the brain.

Diabetes is a Greek word that means “to siphon or pass through.” Mellitus is a Latin word meaning honey or sweet. The disease diabetes mellitus is one in which an individual siphons large volumes of urine with a high glucose level. It is a disease of hyperglycemia characterized by the absolute lack of insulin or a relative lack of cellular insensitivity to insulin. Based on recent epidemiological evidence, the number of people afflicted with diabetes around the globe, currently nearly 200 million, is expected to increase to over 330 million by the year 2025. Reasons for the increase include longer life expectancy and higher population growth coupled with increased rates of obesity associated with urbanization and reliance on processed foods. In the United States, of the 18.2 million persons with diabetes (6.3% of the population), nearly one third are unaware that they have the disease. It is further projected that 57 million people in the United States have prediabetes.

Tests used to diagnose diabetes include the fasting plasma glucose (FPG) test and the oral glucose tolerance test (OGTT). The American Diabetes Association recommends the FPG test because it is faster, easier to perform, and less expensive than the OGTT. An FPG level between 100 and 125 mg/dL is indicative of prediabetes, and an FPG level of 126 mg/dL or more is considered as frank diabetes. For the OGTT, a person’s blood glucose is measured after a fast and 2 hours after drinking a glucose-rich beverage. A 2-hour OGTT between 140 and 199 mg/dL indicates prediabetes; a level of 200 mg/dL or higher indicates diabetes. Providing a range of values indicative of prediabetes allows for earlier intervention in patients at risk of developing frank diabetes. Early intervention is extremely important because, at the time of diagnosis of type 2 diabetes, 20% of patients already have retinal damage, 8% have renal dysfunction, and 9% have neurologic symptoms. Even if the FPG is within normal limits, an OGTT should be conducted if the individual has risk factors for prediabetes. Box 16-1 includes risk factors identified by the American Diabetes Association.