CMAJ : Canadian Medical Association Journal | 2021
Possible association between diabetic ketoacidosis and use of sodium-glucose co-transporter 2 inhibitor in a 17-year-old youth with type 2 diabetes
Abstract
CMAJ | SEPTEMBER 7, 2021 | VOLUME 193 | ISSUE 35 E1385 A 17-year-old male with known type 2 diabetes (T2DM) presented to the emergency department with lethargy, tachypnea and severe abdominal pain that followed a 5-day history of nausea and vomiting. Three years earlier, the patient received a diagnosis of T2DM based on Diabetes Canada criteria.1 At the time of diagnosis, he had intermittent hyperglycemia, a high 2-hour glucose reading on his oral glucose tolerance test (20.5 [normal < 11.1] mmol/L) and a negative GAD65 antibody level (< 3.0 [normal < 5.0] U/mL). His high body mass index (31.9, > 97th percentile), the presence of acanthosis nigricans and an elevated fasting insulin level (277 [normal 35–140] pmol/L), although not diagnostic, were supportive of a diagnosis of T2DM. The patient began dietary and lifestyle interventions. Medical therapy escalated since diagnosis to include metformin and insulin owing to suboptimal glycemic control. A timeline of events is shown in Figure 1. The patient completed diabetes self-management education that included information on nutrition, insulin, hypoglycemia, hyperglycemia, management during an intercurrent illness and ketone management according to standard-of-care clinical practice guidelines. Despite this, his hemoglobin A1c (HbA1c) averaged 9%. His diabetes self-management was characterized by fingerstick glucose monitoring 0–2 times daily, frequent insulin omission and suboptimal adherence with metformin. His GAD65 antibody level remained negative. He had had no episodes of diabetic ketoacidosis (DKA) or severe hypoglycemia. Two months before presentation, the patient’s primary care provider prescribed canagliflozin (a sodium-glucose co-transporter 2 [SGLT-2] inhibitor) starting at 100 mg/d and titrated to 300 mg/d. His prescribed therapy also included metformin (1500 mg at bedtime), insulin glargine (30 units at bedtime) and insulin lispro (1 unit for 3 g of carbohydrate with meals and snacks). At the time our patient presented to hospital he reported that 5 days earlier, on day 1 of his illness, he had decreased his prandial insulin on his own volition because of “low” blood glucose (about 8 mmol/L). He was fearful of hypoglycemia because of decreased intake and vomiting, which led him to stop taking his insulin and metformin; he continued to take canagliflozin. He had not monitored blood glucose or ketones for the 5 days before his presentation to hospital, nor used the telephone assistance service provided by the diabetes centre. On initial assessment, the patient had the following vital signs: heart rate of 130 beats/min, blood pressure of 146/92 mm Hg, respiratory rate of 32 breaths/min with Kussmaul respiration, oxygen saturation of 99% on room air, body temperature of 36.7°C and a Glasgow Coma Scale score of 15. He was pale, with sunken eyes, dry mucous membranes and abdominal tenderness with no features of peritonitis. The patient had a serum glucose level of 17.4 (normal 3.3– 11.0) mmol/L. Venous blood gas analysis showed pH 6.93 (normal 7.30–7.40), anion gap 20 (normal 4–16) mmol/L, bicarbonate 4.8 (normal 20–32) mmol/L and lactate 2.4 (normal 0.5–2.2) mmol/L. His β-hydroxybutyrate level was elevated at 4.3 (normal < 0.4) mmol/L, as was serum osmolality at 310 (normal 280–300) mmol/kg. There were no indicators of substance abuse or infection on history or physical examination; urine and blood cultures were not requested. We diagnosed DKA and provided treatment according to the institutional standard pediatric DKA protocol. We stopped canagliflozin as it was thought to be a substantial contributing factor for our PRACTICE | CASES CPD