Principles of Biochemistry Volume 3 - A. Lehninger 1985

Selected Aspects of Human Biochemistry
Digestion, Nutrient Transport, and Metabolic Interrelationships
Diagnosis and treatment of diabetes mellitus rely on biochemical assay data

Because biochemical analysis of various Blood and urine components provides valuable insight into metabolic patterns, it is widely used in both the Diagnosis and Treatment of Metabolic Disorders. A prime example is Diabetes Mellitus, a condition caused by insufficient Insulin secretion or impaired insulin action (a hormone produced by the Pancreas), leading to profound metabolic abnormalities. In the United States, diabetes ranks as the third leading cause of death. It is highly prevalent: nearly 5% of the U.S. population exhibits some degree of impaired glucose METABOLISM, indicative of either overt diabetes or a predisposition toward it. Essentially, diabetes is a group of conditions characterized by disrupted regulatory activity of insulin, which can stem from various causes. Furthermore, glucose metabolism can be influenced by Other Hormones. While the onset of diabetes is partly genetic, viral infections may also play a contributory role. There are two primary types of diabetes: juvenile-onset and adult-onset. The former manifests at an early age and rapidly progresses to a severe form. In contrast, the latter develops slowly, presents with mild symptoms, and often goes entirely unnoticed. Juvenile-onset diabetes is treated with insulin injections; throughout the patient's life, a careful balance must be maintained between glucose intake and the administered insulin dose. Biochemical blood and urine analyses are critical for diagnosing and managing diabetes, which causes severe metabolic disturbances (Table 24-6).

Class="center">Table 24-6. Major changes in blood and urine composition in uncompensated diabetes mellitus

The hallmark symptoms of diabetes—persistent thirst and frequent urination (polyuria)—are accompanied by a high fluid intake (polydipsia). These changes are driven by The excretion of large amounts of glucose in the urine (glucosuria). The Latin term diabetes mellitus translates to “passing sweet urine in excessive amounts.” In cases of severe uncompensated diabetes, the 24-hour urinary glucose excretion can exceed 100 g, whereas in healthy individuals, glucose appears in the urine only in trace amounts. The large volume of urine in diabetic patients reflects the fact that the Kidneys must excrete extra Water along with the glucose, as their capacity to concentrate dissolved urinary solutes has a definite limit. Measuring urinary glucose over a 24-hour period serves as one of the diagnostic tests for diabetes.

However, determining blood glucose levels and observing how these levels change following glucose ingestion are of far greater significance.

In diabetic patients, blood glucose concentration is typically elevated, a condition known as hyperglycemia. In very severe cases of uncompensated diabetes, blood glucose can reach exceptionally high levels—up to 100 mM, which is 25 times the normal value. In moderate diabetes, blood glucose concentration may differ very little from normal. A more sensitive diagnostic test in such cases is the glucose tolerance test, conducted as follows: the patient drinks a Glass of water containing 100 g of dissolved glucose on an empty Stomach, and blood glucose concentrations are measured before and 30 minutes after ingestion. In a healthy individual, glucose is rapidly assimilated, and its blood concentration during the test rises to no more than 9–10 mM. This is because the surge in blood glucose stimulates insulin secretion by the pancreas, which in turn increases The rate of glucose uptake by Tissues. Normally, little to no glucose appears in the urine during this process (Fig. 24-24).

In contrast, diabetic patients may already exhibit high fasting blood glucose levels, and the glucose tolerance test reveals impaired glucose utilization. Blood glucose concentration can easily exceed the renal threshold of approximately 10 mM, leading to glucosuria, with elevated levels persisting in the blood for several hours (Fig. 24-24). A delayed return of blood glucose to baseline values indicates impaired insulin secretion in response to rising blood glucose levels.

Hyperglycemia and glucosuria point to yet another profound metabolic shift in diabetes mellitus: the near-complete cessation of The conversion of excess glucose into Fatty acids, which are normally stored as triacylglycerols. Patients with severe diabetes experience weight loss despite consuming a high-calorie diet. Rather than being stored as fat, excess glucose in these patients is simply excreted in the urine.

Fig. 24-24. Glucose tolerance curves in healthy individuals and diabetic patients. In a healthy person, following the ingestion of a standard amount of glucose, blood glucose levels may double but quickly decline as insulin secretion increases in response to the rise in blood glucose. For a brief period, blood glucose drops slightly below the initial baseline due to a lag phase, during which circulating insulin levels remain elevated even though blood glucose has already normalized. In diabetic patients, baseline blood glucose is very high (in this case, near the renal threshold). After consuming a standard amount of glucose, the blood sugar level spikes immediately and, unlike in healthy individuals, remains elevated for a prolonged period due to insufficient insulin secretion, returning to baseline only very slowly. When blood glucose reaches its peak in a diabetic patient, significant amounts of glucose are excreted in the urine.