Background

This report describes an uncommon presentation of diabetic ketoacidosis (DKA). The patient was brought into the emergency department (ED) by her husband in a drowsy and minimally communicative state and could only provide limited history. Physical examination was also unremarkable. Blood investigations taken at the ED were severely lipaemic and appeared strawberry pink. The high lipaemic index appeared to cause derangements in point-of-care tests (POCT). Laboratory tests also took up to three times the usual duration to return, and multiple parameters had to be rejected in view of the additional centrifugation required. These delays and paucity of information resulted in a diagnostic challenge. The patient was eventually diagnosed with DKA with severe hypertriglyceridaemia (HT), intubated for airway protection, and managed with fluid resuscitation and intravenous insulin.

When faced with abnormally coloured blood in a critically ill patient, differentials to consider include cyanide poisoning, dyshaemoglobinaemia (eg, carboxyhaemoglobin and methaemoglobinaemia), lipaemia and drug overdose. Severe lipaemia may affect the findings and accuracy of POCT and laboratory tests. A review of the effects of lipaemia on POCT and blood tests will be discussed.

Case presentation

A 54-year-old woman with a medical history of type 2 diabetes mellitus (T2DM) was brought in with an acute onset of shortness of breath and drowsiness. One year before presentation, she had stopped her metformin and subcutaneous insulin against medical advice and started adopting lifestyle modifications, including regular exercise and a modified diet comprising mostly of fruits and salads with intermittent fasting from 09:00 to 21:00 daily. She had also started taking traditional Chinese medications, specifically fish oil, black garlic and lingzhi. Six months in, she started experiencing polydipsia, back and thigh aches, and significant intentional weight loss of 27% (from 52 kg to 38 kg). Her husband also started to notice atrophy of her leg muscles associated with a slow gait and difficulty climbing stairs. She was otherwise well and did not have any other known medical conditions. She did not have a family history of hyperlipidaemia. There was no history of drug overdose, self-harm or exposure to smoke or fumes.

On presentation, she was noted to be dehydrated and drowsy with a Glasgow Coma Scale of 6 (E1V1M4). The patient was also noted to be in sinus tachycardia and tachypnoea with a heart rate of 125, a respiratory rate of 28 and a blood pressure of 157/113. She was otherwise afebrile and saturating well on room air. The patient appeared cachexic and malnourished. Physical examination was otherwise unremarkable with equal and reactive pupils, no pink skin or bright red lips, and no signs of pancreatitis.

Investigations

Blood samples were lipaemic and appeared strawberry pink (figures 1 and 2). POCT arterial blood gas and electrolytes were performed with an Abbott i-STAT System using CG4+ and CHEM8+ test cartridges, respectively, which revealed a high anion gap metabolic acidosis (HAGMA; anion gap 16.5) attributed to lactic acidosis and ketosis (serum ketones 16.47 mmol/L and lactate 3.47 mmol/L) with inadequate respiratory compensation and hyperkalaemia (table 1, S/N 1). In view of concerns of POCT accuracy in the setting of profound lipaemia, a second POCT was done 30 min later, which suggested hypokalaemia instead (table 1, S/N 3). The electrolytes laboratory panel taken at the same time as the first POCT performed via indirect ion-selective electrochemistry (ISE) and was eventually reported only 3 hours after first presentation (compared with 1 hour in a typical sample) in view of need for extensive centrifugation. This revealed HAGMA (anion gap 44.0, delta gap 1.6) with normokalaemia (Serum glucose 31.5 mmol/L, urea 7.2 mmol/L, serum osmolality 312 mOsm/kg (calculating formula: 2×(Na)+(glucose)+(urea); usual range 270–285)) (table 1, S/N 2).

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Figure 1

Clinical photograph of this patient’s blood taken on presentation in the emergency department (colours not digitally edited).

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Figure 2

Demonstration of patient’s blood separating into two distinct layers over time. The distinct opaque supernatant is caused by the precipitation of a high concentration of triglycerides in the blood.

Several tests were also rejected as the blood samples that remained suitable for analysis were insufficient after discarding the lipid supernatant. The remaining laboratory investigations returned at various timings from 30 min to 3 hours post venipuncture and demonstrated severe hyperlipidaemia and HT with a total serum cholesterol of 47.07 mmol/L (usual range 0.00–5.20 mmol/L) and serum triglycerides (TG) of 267.66 (0.00–2.20 mmol/L). (The patient’ high-density lipoprotein and serum low-density lipoprotein were 0.28 mmol/L (1.00–1.60 mmol/L) and 3.85 mmol/L (0.00–3.30 mmol/L), respectively.) There was no significant biochemical evidence of pancreatitis. Her glycated haemoglobin was 8.2%. Serum troponin, liver function tests, thyroid function tests, creatine kinase, paracetamol and salicylate levels, carboxyhaemoglobin, and calcium, magnesium and phosphate levels returned normal. A urine full examination, microscopic examination (UFEME) returned positive for glucose 4+, ketones 4+ and proteins 4+. An ECG was done, which demonstrated sinus tachycardia and no signs of hyperkalaemia or hypokalaemia. Chest X-ray (CXR) and abdominal X-ray as well as CT brain imaging were grossly normal.

Differential diagnosis

In general, the differentials of acute dyspnoea can be broadly classified into cardiovascular, respiratory and metabolic causes. Cardiovascular causes include acute coronary syndrome, cardiac tamponade and heart failure. Respiratory causes are more extensive and can be further subdivided into upper and lower airway aetiologies—upper airway causes comprising largely of obstructive pathologies, such as anaphylaxis and foreign body ingestions, and lower airway causes, including pneumothorax, pulmonary embolism and pulmonary infections. Examples of metabolic causes include, but are not limited to, metabolic acidosis (lactic acidosis and uraemia), thyrotoxicosis and drug overdose.

The patient had a significant medical history of T2DM requiring insulin, which she was non-compliant to. This resulted in symptoms of polydipsia, weight loss and muscle atrophy. On examination, she also appeared cachectic and malnourished. Blood tests demonstrated hyperglycaemia, ketosis, lactic acidosis and HT, and her UFEME returned positive for glucosuria, ketonuria and proteinuria. These led us to the eventual diagnosis of severe DKA with HT secondary to medication non-compliance and sepsis of unknown origin. Of note, there were no other complications of poorly controlled diabetes noted, such as diabetic kidney disease (serum creatinine 36 µmol/L) and ischaemic strokes, and no complications of HT, such as pancreatitis, lipaemia retinalis and cerebral oedema.1–3Starvation ketoacidosis was a consideration in view of the patient’s history of dietary restriction, weight loss and muscle wasting. However, such patients tend to have a low-to-normal blood glucose reading at presentation.4 In our opinion, her weight loss and muscle wasting were more likely contributed by catabolic states observed in DKA.

Treatment

Although investigation results were delayed, the patient was managed expediently according to the tenets of critical care in a ‘first principles’ approach, and a definitive airway was secured in view of the patient’s drowsiness. After the patient was stabilised, she was reassessed and additional corroborative history was taken from her spouse. She was subsequently admitted to the intensive care unit (ICU) where she was treated as for severe DKA and sepsis precipitated by Escherichia coli bacteriaemia. She was resuscitated with 7 L of fluids within the first day of admission and started on intravenous meropenem and a continuous insulin infusion. Her lactic acidosis resolved within day 2 of admission (0.71 mmol/L from 3.47 mmol/L at admission) while her ketoacidosis resolved over 3 days. She was successfully weaned off intravenous insulin infusion on day 4 to subcutaneous insulin, and extubated and transferred out of the ICU on the same day. As of the time of transfer, she had been started on statins and fibrates and her HT and hypercholesterolaemia had improved. Her blood cultures returned positive for pansensitive E. coli while her urine cultures returned negative. A CXR and contrasted CT of her abdomen and pelvis was performed, but returned negative for any obvious source of infection.

A multidisciplinary approach was adopted, and the patient was referred to endocrinology and renal medicine for further management, insulin titration and chronic outpatient follow-up of her diabetes. She was also reviewed by the hospital dietician for dietary and nutrition management, as well as occupational therapists and physiotherapists for rehabilitation and muscle recovery. The patient was educated on her condition and the importance of medication compliance to mitigate risks of recurrence.5 Her DKA and HT improved throughout her inpatient stay and she was eventually discharged well on day 18 of admission. As of the time of discharge, her total serum cholesterol and TG had downtrended from 47.07 mmol/L to 11.69 mmol/L and 267.66 mmol/L to 0.78 mmol/L, respectively.

Outcome and follow-up

The patient remains asymptomatic and well at the time of writing. She has been compliant to her insulin injections and other diabetes medications. Outpatient follow-up investigations performed 1 month after discharge returned normal (total serum cholesterol 5.22 mmol/L, TG 0.45 mmol/L, random urine protein <0.04 mg/dL and UFEME negative for glucose and ketones). She did not experience any other complications of poorly controlled diabetes, such as neuropathy and retinopathy. She will continue to be on routine outpatient follow-up with endocrinology for her diabetes management.