What are the treatment options for Type 2 Diabetes Mellitus (T2DM) with diabetic ketoacidosis (DKA)?

From the Guidelines

Type 2 diabetes with ketoacidosis (DKA) should be treated with hospital admission for intravenous fluids, insulin therapy, and electrolyte management, prioritizing restoration of circulatory volume and tissue perfusion, resolution of ketoacidosis, and correction of electrolyte imbalance and acidosis, as recommended by the most recent guidelines 1.

Key Considerations

• Management goals include restoration of circulatory volume and tissue perfusion, resolution of ketoacidosis, and correction of electrolyte imbalance and acidosis.
• In critically ill and mentally obtunded individuals with DKA, continuous intravenous insulin is the standard of care.
• Successful transition from intravenous to subcutaneous insulin requires administration of basal insulin 2–4 h before the intravenous insulin is stopped to prevent recurrence of ketoacidosis and rebound hyperglycemia.
• There is no significant difference in outcomes for intravenous human regular insulin versus subcutaneous rapid-acting analogs when combined with aggressive fluid management for treating mild or moderate DKA.

Treatment Approach

• Initially, normal saline is administered at 15-20 mL/kg/hour for the first hour, then adjusted based on hydration status.
• Insulin therapy begins with an IV bolus of regular insulin (0.1 units/kg) followed by continuous infusion at 0.1 units/kg/hour until blood glucose reaches 200-250 mg/dL, then reduced to 0.02-0.05 units/kg/hour.
• Potassium replacement is crucial when levels fall below 5.2 mEq/L, typically given as 20-30 mEq/L in IV fluids.
• Once the patient stabilizes (glucose <200-250 mg/dL, bicarbonate >18 mEq/L, pH >7.3), transition to subcutaneous insulin can begin.

Long-term Management

• Basal-bolus insulin therapy, metformin (starting at 500 mg daily, increasing to 1000 mg twice daily as tolerated), and possibly SGLT-2 inhibitors or GLP-1 receptor agonists.
• Regular monitoring of blood glucose, ketones, and electrolytes is essential during treatment to prevent complications like cerebral edema or hypoglycemia, as supported by recent studies 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Regulation of glucose metabolism is the primary activity of insulin. Insulin lowers blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulins inhibit lipolysis, proteolysis, and gluconeogenesis, and enhance protein synthesis and conversion of excess glucose into fat Administered insulin, including Humulin R U-100, substitutes for inadequate endogenous insulin secretion and partially corrects the disordered metabolism and inappropriate hyperglycemia of diabetes mellitus, which are caused by either a deficiency or a reduction in the biologic effectiveness of insulin When administered in appropriate doses at prescribed intervals to patients with diabetes mellitus, Humulin R U-100 restores their ability to metabolize carbohydrates, proteins and fats.

The FDA drug label does not answer the question about type 2 diabetes with ketoacidosis.

From the Research

Type 2 Diabetes with Ketoacidosis

• Type 2 diabetes can lead to diabetic ketoacidosis (DKA), a life-threatening complication characterized by hyperglycemia, metabolic acidosis, and ketosis 2, 3, 4, 5, 6
• DKA is more common in patients with type 1 diabetes, but almost a third of cases occur in patients with type 2 diabetes 2
• The most common precipitating causes for DKA include infections, new diagnosis of diabetes, and nonadherence to insulin therapy 2, 3, 5
• Clinicians should be aware of the occurrence of DKA in patients prescribed sodium-glucose co-transporter 2 inhibitors 2, 3
• Proper management of DKA requires hospitalization for aggressive intravenous fluids, insulin therapy, electrolyte replacement, and identification and treatment of the underlying precipitating event 2, 3, 4, 5

Diagnosis and Treatment

• DKA is diagnosed by the triad of hyperglycemia, metabolic acidosis, and elevated serum or urine ketones 3, 4, 5
• Treatment involves fluid and electrolyte replacement, insulin, treatment of precipitating causes, and close monitoring to adjust therapy and identify complications 2, 3, 4, 5
• Electrolytes, phosphate, blood urea nitrogen, creatinine, urinalysis, complete blood cell count with differential, A1C, and electrocardiography should be evaluated for all patients diagnosed with DKA 3

Prevention and Management

• Prevention strategies include identifying diabetes before DKA develops, educating patients to manage high-risk situations, and ensuring uninterrupted access to therapies for diabetes 2, 3, 5, 6
• Future episodes of DKA can be reduced through patient education programs focusing on adherence to insulin and self-care guidelines during illness and improved access to medical providers 2
• Novel approaches to patient education incorporating a variety of healthcare beliefs and socioeconomic issues are critical to an effective prevention program 5