How does insulin deficiency cause osmotic diuresis?

From the Guidelines

Insulin deficiency causes osmotic diuresis by leading to hyperglycemia, which exceeds the renal threshold, resulting in glycosuria and subsequent increased urine output due to the osmotic effect of glucose in the renal tubules. When insulin is insufficient, cells cannot properly take up glucose from the bloodstream, leading to hyperglycemia (high blood sugar) 1. As blood glucose levels rise above the renal threshold (approximately 180 mg/dL), the kidneys cannot reabsorb all the filtered glucose, causing glucose to spill into the urine (glycosuria) 1. Glucose acts as an osmotic agent in the renal tubules, drawing water with it and preventing water reabsorption. This results in increased urine output (polyuria), a hallmark symptom of uncontrolled diabetes.

Some key points to consider in this process include:

• The role of insulin in glucose uptake and the consequences of its deficiency on blood glucose levels 1
• The renal threshold for glucose and how its exceedance leads to glycosuria 1
• The osmotic effect of glucose in the renal tubules and its impact on water and electrolyte balance
• The clinical manifestations of osmotic diuresis, including polyuria, polydipsia, and weight loss, as well as potential electrolyte imbalances

The severity of osmotic diuresis correlates with the degree of hyperglycemia, making blood glucose control through insulin therapy or other diabetes medications essential to prevent this process 1. Understanding the pathogenesis of hyperglycemic crises, such as diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS), also highlights the importance of managing insulin deficiency and its consequences on glucose metabolism and osmolality 1.

From the Research

Insulin Deficiency and Osmotic Diuresis

• Insulin deficiency can lead to an increase in blood glucose levels, which can exceed the renal threshold for glucose reabsorption 2.
• When the renal threshold is exceeded, glucose is lost in the urine, leading to an osmotic diuresis and subsequent dehydration if oral intake is insufficient 2.
• The physiology of fluid loss in diabetic ketoacidosis (DKA) is complex, but it is summarized as follows:
  • As blood glucose levels rise, the renal threshold for active glucose reabsorption is exceeded.
  • This leads to glucose loss in the urine.
  • The glucose loss in the urine causes an osmotic diuresis.
  • The osmotic diuresis leads to dehydration if oral intake is insufficient.
• Further losses are accounted for by hyperventilation, sweating, and vomiting 2.

Role of Insulin in Glucose Regulation

• Insulin plays a crucial role in regulating blood glucose levels by facilitating glucose uptake in cells 3.
• In the absence of insulin, glucose builds up in the blood, leading to hyperglycemia and subsequent osmotic diuresis 3.
• The use of rapid-acting insulin analogs, such as insulin aspart and lispro, can help to attenuate postprandial glucose excursions and reduce the risk of osmotic diuresis 4, 5, 6.

Comparison of Insulin Types

• Rapid-acting insulin analogs, such as insulin aspart and lispro, have a faster onset of action and a shorter duration of action compared to human soluble insulin 4, 5, 6.
• Ultra-rapid-acting insulins, such as insulin aspart and lispro, have been shown to be as efficacious and safe as rapid-acting insulins, with a favorable effect on postprandial glucose control 5.
• The choice of insulin type and regimen should be individualized based on the patient's specific needs and circumstances 6.