What are the causes of hyperglycemia (high blood sugar) and metabolic acidosis?

From the Guidelines

Hyperglycemia and metabolic acidosis are primarily caused by absolute or relative insulin deficiency, leading to the accumulation of ketone bodies in the blood and subsequent metabolic acidosis, as seen in diabetic ketoacidosis (DKA) 1. The causes of hyperglycemia and metabolic acidosis can be understood by examining the pathophysiology of DKA.

• Hyperglycemia refers to high blood glucose levels, typically above 180 mg/dL.
• Metabolic acidosis is an abnormally high acid concentration in the blood and body tissues, indicated by a blood pH below 7.35. The primary treatment for these conditions involves insulin therapy and fluid replacement.
• For DKA, treatment should start with IV fluid resuscitation using normal saline at 15-20 mL/kg/hr initially, followed by insulin therapy with regular insulin at 0.1 units/kg/hr IV 1.
• Blood glucose should be monitored hourly, and when levels fall below 200-250 mg/dL, add dextrose to IV fluids while continuing insulin to clear ketones.
• Electrolyte replacement, particularly potassium, is essential as levels often drop with treatment. The connection between hyperglycemia and acidosis occurs because without sufficient insulin, the body cannot use glucose for energy and breaks down fat instead, producing ketone bodies that cause acidosis 1. The most recent and highest quality study recommends individualization of treatment based on a careful clinical and laboratory assessment, with management goals including restoration of circulatory volume and tissue perfusion, resolution of hyperglycemia, and correction of electrolyte imbalance and acidosis 1.

From the FDA Drug Label

Hyperglycemia (too much glucose in the blood) may develop if your body has too little insulin Hyperglycemia can be brought about by any of the following: Omitting your insulin or taking less than your doctor has prescribed. Eating significantly more than your meal plan suggests. Developing a fever, infection, or other significant stressful situation. Hyperglycemia, diabetic ketoacidosis, or hyperosmolar coma may develop if the patient takes less Humulin R U-100 than needed to control blood glucose levels This could be due to increases in insulin demand during illness or infection, neglect of diet, omission or improper administration of prescribed insulin doses or use of drugs that affect glucose metabolism or insulin sensitivity.

The causes of hyperglycemia (high blood sugar) include:

• Omitting insulin or taking less than prescribed
• Eating more than the meal plan suggests
• Developing a fever, infection, or other stressful situation
• Increases in insulin demand during illness or infection
• Neglect of diet
• Omission or improper administration of prescribed insulin doses
• Use of drugs that affect glucose metabolism or insulin sensitivity

The causes of metabolic acidosis (specifically diabetic ketoacidosis) include:

• Prolonged hyperglycemia
• Infection or illness
• Omitting insulin or taking less than prescribed
• Use of drugs that affect glucose metabolism or insulin sensitivity 2 2

From the Research

Causes of Hyperglycemia and Metabolic Acidosis

The causes of hyperglycemia (high blood sugar) and metabolic acidosis can be attributed to several factors, including:

• Insulin deficiency, which leads to increased rates of hepatic ketogenesis and gluconeogenesis, resulting in hyperglycemia and ketonemia 3
• Increased levels of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone, which contribute to the development of diabetic ketoacidosis and the hyperosmolar hyperglycemic state 4, 5
• Precipitating factors, such as infections, new diagnosis of diabetes, and nonadherence to insulin therapy, which can trigger the onset of diabetic ketoacidosis 4, 6

Pathogenesis of Diabetic Ketoacidosis

The pathogenesis of diabetic ketoacidosis involves:

• Absolute insulin deficiency, which leads to increased lipolysis and production of ketone bodies, resulting in metabolic acidosis 5
• Increased gluconeogenesis and accelerated glyconeogenesis, which contribute to the development of hyperglycemia 5
• Electrolyte imbalance, which can exacerbate the condition 4, 6

Risk Factors for Diabetic Ketoacidosis

The risk factors for diabetic ketoacidosis include:

• Type 1 and type 2 diabetes mellitus 4, 6
• New diagnosis of diabetes 6
• Nonadherence to insulin therapy 6
• Infections 6
• Prescription of sodium-glucose co-transporter 2 inhibitors 6