Diagnosis and Treatment > Signs and Symptoms
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Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
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Summary
We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non–small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home. He subsequently has developed likely autoimmune thyroiditis and autoimmune encephalitis.
Learning points:
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Glycemic surveillance in patients receiving immune checkpoint inhibitors is recommended.
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Early glycemic surveillance after commencement of anti-programmed cell death-1 (PD-1) inhibitors may be indicated in selected populations, including patients with underlying type 2 diabetes mellitus and positive anti-glutamic acid decarboxylase (GAD) antibody.
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Sodium-glucose co transporter-2 (SGLT2) inhibitors should be used with caution in patients on immunotherapy.
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Summary
Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.
Learning points:
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Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.
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Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.
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Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.
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Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.
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Summary
Ketoacidosis occurring during lactation has been described infrequently. The condition is incompletely understood, but it appears to be associated with a combination of increased metabolic demands during lactation, reduction in carbohydrate intake and acute illness. We present a case of a 27-year-old woman, 8 weeks post-partum, who was exclusively breastfeeding her child whilst following a low carbohydrate diet. She developed gastroenteritis and was unable to tolerate an oral diet for several days. She presented with severe metabolic acidosis on admission with a blood 3-hydroxybutyrate of 5.4 mmol/L. She was treated with intravenous dextrose and intravenous sodium bicarbonate, and given dietary advice to increase her carbohydrate intake. She made a rapid and full recovery. We provide a summary of the common causes of ketoacidosis and compare our case with other presentations of lactation ketoacidosis.
Learning points:
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Ketoacidosis in the lactating woman is a rare cause of raised anion gap metabolic acidosis.
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Low carbohydrate intake, starvation, intercurrent illness or a combination of these factors could put breastfeeding women at risk of ketoacidosis.
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Ketoacidosis in the lactating woman has been shown to resolve rapidly with sufficient carbohydrate intake and intravenous dextrose.
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Early diagnosis and prompt treatment are essential because the condition is reported to be reversible with a low chance of recurrence with appropriate dietary advice.
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Search for other papers by Francis M Finucane in
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Summary
We describe three patients presenting with diabetic ketoacidosis secondary to ketosis prone type 2, rather than type 1 diabetes. All patients were treated according to a standard DKA protocol, but were subsequently able to come off insulin therapy while maintaining good glycaemic control. Ketosis-prone type 2 diabetes (KPD) presenting with DKA has not been described previously in Irish patients. The absence of islet autoimmunity and evidence of endogenous beta cell function after resolution of DKA are well-established markers of KPD, but are not readily available in the acute setting. Although not emphasised in any current guidelines, we have found that a strong family history of type 2 diabetes and the presence of cutaneous markers of insulin resistance are strongly suggestive of KPD. These could be emphasised in future clinical practice guidelines.
Learning points:
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Even in white patients, DKA is not synonymous with type 1 diabetes and autoimmune beta cell failure. KPD needs to be considered in all patients presenting with DKA, even though it will not influence their initial treatment.
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Aside from markers of endogenous beta cell function and islet autoimmunity, which in any case are unlikely to be immediately available to clinicians, consideration of family history of type 2 diabetes and cutaneous markers of insulin resistance might help to identify those with KPD and are more readily apparent in the acute setting, though not emphasised in guidelines.
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Consideration of KPD should never alter the management of the acute severe metabolic derangement of DKA, and phasing out of insulin therapy requires frequent attendance and meticulous and cautious surveillance by a team of experienced diabetes care providers.
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Search for other papers by Nobuo Yaegashi in
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Summary
Diabetic ketoacidosis (DKA) during pregnancy is a serious complication in both mother and fetus. Most incidences occur during late pregnancy in women with type 1 diabetes mellitus. We report the rare case of a woman with type 1 diabetes mellitus who had normal glucose tolerance during the first trimester but developed DKA during late pregnancy. Although she had initially tested positive for screening of gestational diabetes mellitus during the first trimester, subsequent diagnostic 75-g oral glucose tolerance tests showed normal glucose tolerance. She developed DKA with severe general fatigue in late pregnancy. The patient's general condition improved after treatment for ketoacidosis, and she vaginally delivered a healthy infant at term. The presence of DKA caused by the onset of diabetes should be considered, even if the patient shows normal glucose tolerance during the first trimester.
Learning points
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The presence of DKA caused by the onset of diabetes should be considered, even if the patient shows normal glucose tolerance during the first trimester.
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Symptoms including severe general fatigue, nausea, and weight loss are important signs to suspect DKA. Findings such as Kussmaul breathing with ketotic odor are also typical.
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Urinary test, atrial gas analysis, and anion gap are important. If pH shows normal value, calculation of anion gap is important. If the value of anion gap is more than 12, a practitioner should consider the presence of metabolic acidosis.
