CLINICAL RECOGNITION

Omission of insulin and infection are the two most common precipitants of DKA. Noncompliance may account for up to 44% of DKA presentations; while infection is less frequently observed in DKA patients.

Acute medical illnesses involving the cardiovascular system (myocardial infarction, stroke, acute thrombosis) and gastrointestinal tract (bleeding, pancreatitis), diseases of endocrine axis (acromegaly, Cushing`s syndrome, hyperthyroidism) and impaired thermoregulation or recent surgical procedures can contribute to the development of DKA by causing dehydration, increase in insulin counterregulatory hormones, and worsening of peripheral insulin resistance.

Medications such as diuretics, beta-blockers, corticosteroids, second-generation anti-psychotics, anti-convulsants, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and/or immune checkpoint inhibitors may affect carbohydrate metabolism and volume status and, therefore, could precipitate DKA.

Other factors: psychological problems, eating disorders, insulin pump malfunction, and drug abuse. It is now recognized that new onset T2DM can manifest with DKA. These patients are obese, mostly African Americans or Hispanics and have undiagnosed hyperglycemia, impaired insulin secretion, and insulin action. A recent report suggests that cocaine abuse is an independent risk factor associated with DKA recurrence.

PATHOPHYSIOLOGY

Insulin deficiency, increased insulin counter-regulatory hormones (cortisol, glucagon, growth hormone, and catecholamines) and peripheral insulin resistance lead to hyperglycemia, dehydration, ketosis, and electrolyte imbalance which underlie the pathophysiology of DKA.

Hyperglycemia of DKA evolves through accelerated gluconeogenesis, glycogenolysis, and decreased glucose utilization – all due to absolute insulin deficiency. Of note, diabetes patients who developed DKA while treated with SGLT-2 inhibitors can present without hyperglycemia, i.e., with euglycemic DKA. Due to increased lipolysis and decreased lipogenesis, abundant free fatty acids are converted to ketone bodies: β-hydroxybutyrate (β-OHB), acetoacetate, and acetone. Hyperglycemia-induced osmotic diuresis, if not accompanied by sufficient oral fluid intake, leads to dehydration, hyperosmolarity, electrolyte loss, and subsequent decrease in glomerular filtration. With decline in renal function, glycosuria diminishes and hyperglycemia/hyperosmolality worsens. With impaired insulin action and hyperosmolality, utilization of potassium by skeletal muscle is markedly diminished leading to intracellular potassium depletion. Also, potassium is lost via osmotic diuresis causing profound total body potassium deficiency. Therefore, DKA patients can present with broad range of serum potassium concentrations. Nevertheless, a “normal” plasma potassium concentration may indicate that potassium stores in the body are severely diminished and the institution of insulin therapy and correction of hyperglycemia will lead to future hypokalemia.

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

Diagnostic criteria for DKA are presented in Table 1.

DIAGNOSTIC TESTS NEEDED

THERAPY (Figure 1a, 1b, and 1c)

The therapeutic goals of management include optimization of:

• volume status,
• hyperglycemia and ketosis/acidosis,
• electrolyte abnormalities,
• potential precipitating factors.

Steps to follow in early stages of DKA management (Figure 1):

• Start IV fluids after blood sample for biochemistry was sent to laboratory (Fig. 1A);
• Potassium level should be >3.3 meq/L before initiation of insulin therapy (supplement potassium intravenously if needed) (Fig. 1C);
• Initiate insulin therapy only when steps 1-2 are executed (Fig. 1B).

Resolution of DKA:

• Plasma glucose <200-250 mg/dl,
• Serum bicarbonate concentration >18 meq/L,
• Venous blood pH >7.3, and
• Anion gap <10

Fluid therapy: Replace fluid deficit in DKA (~6 L) within 24-36 hours with the goal of 50% volume replacement within first 12 hours.

Insulin Therapy: Transition to subcutaneous insulin by giving long-acting insulin 2 hours before the discontinuation of IV insulin.

Bicarbonate therapy: If pH is < 7.0 or bicarbonate level is < 5 meq/L, administer 100 mmol (2 ampules) of bicarbonate in 200 ml of water with 20 meq of potassium chloride over two hours.

FOLLOW UP: COMPLICATIONS AND DISCHARGE

Hypoglycemia and hypokalemia are the most frequent complications and can be prevented by timely adjustment of insulin dose and frequent monitoring of potassium levels.

Non-anion gap hyperchloremic acidosis occurs due to urinary loss of ketoanions which are needed for bicarbonate regeneration and preferential re-absorption of chloride in proximal renal tubule secondary to intensive administration of chloride-containing fluids and low plasma bicarbonate. The acidosis usually resolves and should not affect treatment course.

Cerebral edema is reported in young adult patients. This condition is manifested by appearance of headache, lethargy, papillary changes, or seizures. Mortality is up to 70%. Mannitol infusion and mechanical ventilation should be used to treat this condition.

Rhabdomyolysis is another possible complication due to hyperosmolality and hypoperfusion.

Pulmonary edema can develop from excessive fluid replacement in patients with CKD or CHF.

Discharge planning should include diabetes education, selection of appropriate insulin regimen that is understood and afforded by the patient, and preparation of set of supplies for the initial insulin administration at home.

REFERENCES

Kitabchi AE, Umpierrez GE, Fisher JN, Murphy MB, and Stentz FB. Thirty years of personal experience in hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. The Journal of clinical endocrinology and metabolism 93: 1541-1552, 2008.http://www.ncbi.nlm.nih.gov/pubmed/18270259

Kitabchi AE, Umpierrez GE, Miles JM, and Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes care 32: 1335-1343, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19564476

Gosmanov AR, Kitabchi AE. Diabetic Ketoacidosis. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-2015 Apr 12