A 12-year-old girl presents to her primary care physician for evaluation of anxiety, panic symptoms, and low BMI. She denies intentional restrictive eating or binging/purging. At 18:34, the chemistry resident on-call is informed by the lab that the patient has a potassium value of 6.6 mmol/L. They are having difficulty reaching the primary care provider, and are wondering if this result could be due to contamination or some other type of laboratory error.
The correct answer is ...
New-onset Type I diabetes mellitus (T1DM).
Based on the potassium and glucose results, the patient was referred to the Emergency Department. Upon presentation to the ED, lab results are notable for sodium of 122 mmol/L, glucose of 896 mg/dL, lactate of 2.4 mmol/L, and beta-hydroxybutyrate of 1.6 mmol/L.
A diabetes diagnosis is confirmed by A1c of 18.0% and glucose of 896 mg/dL. At the time of presentation to the ED, the earlier hyperkalemia has resolved, but the patient is now hyponatremic.
New-onset T1DM, electrolyte abnormalities, and DKA/HHS
Are the observed electrolyte abnormalities consistent with the patient’s condition, or was some sort of laboratory or pre-analytical error involved? Significant electrolyte abnormalities can be associated with acute presentation of T1DM, especially in diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS), which are often the first presentation in new-onset cases of Type I diabetes. Significant hyperkalemia is often seen in DKA/HHS,1,2 and can be attributed to multiple mechanisms, all of which contribute to a shift of potassium from the intracellular to extracellular compartment.
First, the absence of insulin, which activates the Na/K-ATPase at cell membranes and is therefore responsible for maintaining the intracellular potassium gradient, allows the loss of potassium from the intracellular to the extracellular space. Second, the presence of increased extra-cellular osmolarity due to marked hyperglycemia causes efflux of water from cells, accompanied by additional intracellular potassium. Finally, the presence of metabolic acidosis, as in DKA, is associated with extracellular shunting of potassium as hydrogen ions accumulate intracellularly, displacing positively charged potassium ions to balance intracellular and extracellular charge.
The hyponatremia observed upon presentation to the ED would also be consistent with marked hyperglycemia and/or DKA/HHS; increased extracellular osmolarity results in an expansion of the extracellular fluid volume, resulting in a dilutional hyponatremia.3 While pseudohyperkalemia by hemoconcentration due to the combination of fist-clenching and prolonged tourniquet time during phlebotomy is known to occur,4 this mechanism would not explain the other lab abnormalities seen in this case.
The diagnosis of T1DM was established by the presence of marked hyperglycemia, ketosis (urine ketones positive, beta-hydroxybutyrate elevated), and elevated A1c. The patient did not meet the criteria for DKA, not being frankly acidotic (venous pH 7.35) despite the presence of BOHB and an increased anion gap. The patient was also not classified as having HHS, having a calculated serum osmolality of 294 mOsm/kg (RI: 275-295); HHS is generally associated with osmolality in excess of 320 mOsm/kg. The patient was therefore admitted to pediatric general medicine and managed successfully with intravenous fluid administration and subcutaneous insulin. Prompt laboratory diagnosis and follow-up may have prevented a presentation of acute DKA, which can have significant associated morbidity and mortality.5
Additional testing for T1DM
The patient was also found to be positive for antibodies to islet antigen-2 (IA-2). While not necessary for the diagnosis of T1DM in most cases, autoantibodies against islet cell antigens including insulin, IA-2, glutamate decarboxylase 65 (GAD65) and zinc transporter ZnT8, can be helpful in determining an autoimmune etiology. Greater than 95% of patients with T1DM are positive for at least one of these auto-antibodies, and their presence can be helpful for distinguishing between Type 1 and Type 2 diabetes in ambiguous cases, such as late-onset diabetes, adolescent diabetes presenting without ketoacidosis, and adolescent onset diabetes in patients who are overweight or obese.6,7
Benjamin Andress, Ph.D.
Fellow, Clinical Chemistry
Brad Karon, M.D., Ph.D.
Consultant, Clinical Core Laboratory Services
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science