Diagnosis and Treatment > Investigation > C-peptide (blood)

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Akihiko Ando Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan

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Shoichiro Nagasaka Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Kanagawa Japan

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Shun Ishibashi Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan

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Summary

We report a case of a woman with diabetes mellitus caused by a genetic defect in ABCC8-coding sulfonylurea receptor 1 (SUR1), a subunit of the ATP-sensitive potassium (KATP) channel protein. She was diagnosed with diabetes at 7 days after birth. After intravenous insulin drip for 1 month, her hyperglycaemia remitted. At the age of 13 years, her diabetes relapsed, and after that she had been treated by intensive insulin therapy for 25 years with relatively poor glycaemic control. She was switched to oral sulfonylurea therapy and attained euglycaemia. In addition, her insulin secretory capacity was ameliorated gradually.

Learning points:

  • Genetic testing should be considered in any individuals or family with diabetes that occurred within the first year or so of life.

  • Sulfonylurea can achieve good glycaemic control in patients with KATP channel mutations by restoring endogenous insulin secretion, even if they were treated with insulin for decades.

  • Early screening and genetic testing are important to improve the prognosis of patients with neonatal diabetes mellitus arising from ABCC8 or KCNJ11 mutation.

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Ali A Zaied Divisions of Pulmonary and Critical Care Medicine, Mayo Clinic, Jacksonville, Florida, USA

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Halis K Akturk Divisions of Endocrinology, Mayo Clinic, Jacksonville, Florida, USA

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Richard W Joseph Divisions of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, USA

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Augustine S Lee Divisions of Pulmonary and Critical Care Medicine, Mayo Clinic, Jacksonville, Florida, USA

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Summary

Nivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.

Learning points:

  • Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).

  • Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop de novo following administration of anti-PD-1.

  • Because anti-PD-1 works by the activation of T-cells and reduction of ‘self-tolerance’, other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.

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Ploutarchos Tzoulis Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Richard W Corbett Department of Medicine, Imperial College London, London, UK

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Swarupini Ponnampalam Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Elly Baker Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Daniel Heaton Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Triada Doulgeraki Medical School, University of Athens, Athens, Greece

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Justin Stebbing Department of Surgery and Cancer, Imperial College London, London, UK

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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:

  • Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.

  • Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.

  • Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.

  • Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.

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Florence Gunawan Geelong University Hospital, Barwon Health, Geelong, Victoria, Australia

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Elizabeth George
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Adam Roberts
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Summary

Immune checkpoint inhibitors are the mainstay of treatment for advanced melanoma, and their use is being increasingly implicated in the development of autoimmune endocrinopathies. We present a case of a 52-year-old man with metastatic melanoma on combination nivolumab and ipilumimab therapy who developed concurrent hypophysitis, type 1 diabetes mellitus (T1DM) and diabetes insipidus. He presented prior to third cycle of combination treatment with a headache, myalgias and fatigue. Biochemistry and MRI pituitary confirmed anterior pituitary dysfunction with a TSH: 0.02 mU/L (0.5–5.5 mU/L), fT4: 5.2 pmol/L (11–22 pmol/L), fT3: 4.0 pmol/L (3.2–6.4 pmol/L), cortisol (12:00 h): <9 nmol/L (74–286 nmol/L), FSH: 0.7 IU/L (1.5–9.7 IU/L), LH: <0.1 IU/L (1.8–9.2 IU/L), PRL: 1 mIU/L (90–400 mIU/L), SHBG: 34 nmol/L (19–764 nmol/L) and total testosterone: <0.4 nmol/L (9.9–27.8 nmol/L). High-dose dexamethasone (8 mg) was administered followed by hydrocortisone, thyroxine and topical testosterone replacement. Two weeks post administration of the third cycle, he became unwell with lethargy, weight loss and nocturia. Central diabetes insipidus was diagnosed on the basis of symptoms and sodium of 149 mmol/L (135–145 mmol/L). Desmopressin nasal spray was instituted with symptom resolution and normalization of serum sodium. Three weeks later, he presented again polyuric and polydipsic. His capillary glucose was 20.8 mmol/L (ketones of 2.4 mmol), low C-peptide 0.05 nmol/L (0.4–1.5 nmol/L) and HbA1c of 7.7%. T1DM was suspected, and he was commenced on an insulin infusion with rapid symptom resolution. Insulin antibodies glutamic acid decarboxylase (GAD), insulin antibody-2 (IA-2) and zinc transporter-8 (ZnT8) were negative. A follow-up MRI pituitary revealed findings consistent with recovering autoimmune hypophysitis. Immunotherapy was discontinued based on the extent of these autoimmune endocrinopathies.

Learning points:

  • The most effective regime for treatment of metastatic melanoma is combination immunotherapy with nivolumab and ipilumimab, and this therapy is associated with a high incidence of autoimmune endocrinopathies.

  • Given the high prevalence of immune-related adverse events, the threshold for functional testing should be low.

  • Traditional antibody testing may not be reliable to identify early-onset endocrinopathy.

  • Routine screening pathways have yet to be adequately validated through clinical trials.

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Takatoshi Anno Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan

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Hideaki Kaneto Department of Diabetes, Metabolism and Endocrinology, Kawasaki Medical School, Kurashiki, Japan

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Ryo Shigemoto Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan

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Fumiko Kawasaki Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan

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Yasuhiro Kawai Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan

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Noriyo Urata Department of General Internal Medicine 2, Kawasaki Medical School, Okayama, Japan

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Hirofumi Kawamoto Department of General Internal Medicine 2, Kawasaki Medical School, Okayama, Japan

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Kohei Kaku Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan

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Niro Okimoto Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan

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Summary

Hypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores.

Learning points:

  • It is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia.

  • Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in everyday clinical practice.

  • Herein, we reported similar 2 cases of hypoinsulinemic hypoglycemia without diabetes presumably triggered by severe liver injury.

  • In both cases, hypoglycemia was improved by glucose infusion, although their liver injury was not improved.

  • We should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly subjects with low body weight.

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Sarah Y Qian Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Australia

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Matthew J L Hare Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Australia

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Alan Pham Department of Anatomical Pathology, The Alfred Hospital, Melbourne, Australia

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Duncan J Topliss Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Australia
Department of Medicine, Monash University, Melbourne, Australia

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Summary

Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.

Learning points:

  • Hypoglycaemia is defined by Whipple’s triad and can be provoked by fasting or mixed-meal tests.

  • Although uncommon, insulinomas can present with post-prandial hypoglycaemia.

  • In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.

  • Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.

  • Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.

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Ken Takeshima First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Hiroyuki Ariyasu First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Tatsuya Ishibashi First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Shintaro Kawai First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Shinsuke Uraki First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Jinsoo Koh Department of Neurology, Wakayama Medical University, Wakayama,, Japan

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Hidefumi Ito Department of Neurology, Wakayama Medical University, Wakayama,, Japan

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Takashi Akamizu First Department of Internal Medicine, Wakayama Medical University, Wakayama,, Japan

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Summary

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease affecting muscles, the eyes and the endocrine organs. Diabetes mellitus and primary hypogonadism are endocrine manifestations typically seen in patients with DM1. Abnormalities of hypothalamic–pituitary–adrenal (HPA) axis have also been reported in some DM1 patients. We present a case of DM1 with a rare combination of multiple endocrinopathies; diabetes mellitus, a combined form of primary and secondary hypogonadism, and dysfunction of the HPA axis. In the present case, diabetes mellitus was characterized by severe insulin resistance with hyperinsulinemia. Glycemic control improved after modification of insulin sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with testosterone replacement therapy. Notably, body composition analysis revealed increase in muscle mass and decrease in fat mass in our patient. This implies that manifestations of hypogonadism could be hidden by symptoms of myotonic dystrophy. Our patient had no symptoms associated with adrenal deficiency, so adrenal dysfunction was carefully followed up without hydrocortisone replacement therapy. In this report, we highlight the necessity for evaluation and treatment of multiple endocrinopathies in patients with DM1.

Learning points:

  • DM1 patients could be affected by a variety of multiple endocrinopathies.

  • Our patients with DM1 presented rare combinations of multiple endocrinopathies; diabetes mellitus, combined form of primary and secondary hypogonadism and dysfunction of HPA axis.

  • Testosterone treatment of hypogonadism in patients with DM1 could improve body composition.

  • The patients with DM1 should be assessed endocrine functions and treated depending on the degree of each endocrine dysfunction.

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Naoya Toriu Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Masayuki Yamanouchi Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Rikako Hiramatsu Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Noriko Hayami Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Junichi Hoshino Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Akinari Sekine Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Masahiro Kawada Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Eiko Hasegawa Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Tatsuya Suwabe Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Keiichi Sumida Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Toshiharu Ueno Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Naoki Sawa Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan

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Kenichi Ohashi Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan
Department of Pathology, Yokohama City University, Graduate School of Medicine, Yokohama, Japan

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Takeshi Fujii Department of Pathology, Toranomon Hospital, Tokyo, Japan

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Kenmei Takaichi Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan
Okinaka Memorial Institute for Medical Research, Tokyo, Japan

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Motoko Yanagita Department of Nephrology, Kyoto University Graduate School of Medicine, Japan

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Tetsuro Kobayasi Okinaka Memorial Institute for Medical Research, Tokyo, Japan

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Yoshifumi Ubara Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan
Okinaka Memorial Institute for Medical Research, Tokyo, Japan

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Summary

We report the case of a 67-year-old Japanese woman with type 1 diabetes mellitus. At 47 years of age, her hemoglobin A1c (HbA1c) was 10.0%, and she had overt nephropathy. The first renal biopsy yielded a diagnosis of diabetic nephropathy. Intensive glycemic control was initiated and her HbA1c improved to 6.0%. Renal dysfunction showed no progression for 15 years. At 62 years of age, a second renal biopsy was performed. Glomerular lesions did not show progression but tubulointerstitial fibrosis and vascular lesions showed progression compared with the first biopsy. Intensive glycemic control can prevent the progression of glomerular lesions, but might not be effective for interstitial and vascular lesions.

Learning points:

  • Intensive control of blood glucose can prevent the progression of glomerular lesions.

  • Intensive control of blood glucose may not be able to prevent progression of interstitial and vascular lesions.

  • CSII reduces HbA1c without increasing the risk of hypoglycemia.

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Peter Novodvorsky Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

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Emma Walkinshaw Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

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Waliur Rahman Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Valerie Gordon Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Karen Towse Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Sarah Mitchell Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Dinesh Selvarajah Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

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Priya Madhuvrata Department of Obstetrics, Gynaecology and Neonatology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

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Alia Munir Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

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Summary

Bariatric surgery is an effective therapy for obesity but is associated with long-term complications such as dumping syndromes and nutritional deficiencies. We report a case of a 26-year-old caucasian female, with history of morbid obesity and gestational diabetes (GDM), who became pregnant 4 months after Roux-en-Y bypass surgery. She developed GDM during subsequent pregnancy, which was initially managed with metformin and insulin. Nocturnal hypoglycaemia causing sleep disturbance and daytime somnolence occured at 19 weeks of pregnancy (19/40). Treatment with rapid-acting carbohydrates precipitated further hypoglycaemia. Laboratory investigations confirmed hypoglycaemia at 2.2 mmol/L with appropriately low insulin and C-peptide, intact HPA axis and negative IgG insulin antibodies. The patient was seen regularly by the bariatric dietetic team but concerns about compliance persisted. A FreeStyle Libre system was used from 21/40 enabling the patient a real-time feedback of changes in interstitial glucose following high or low GI index food intake. The patient declined a trial of acarbose but consented to an intraveneous dextrose infusion overnight resulting in improvement but not complete abolishment of nocturnal hypoglycaemia. Hypoglycaemias subsided at 34/40 and metformin and insulin had to be re-introduced due to high post-prandial blood glucose readings. An emergency C-section was indicated at 35 + 1/40 and a small-for-gestational-age female was delivered. There have been no further episodes of hypoglycaemia following delivery. This case illustrates challenges in the management of pregnancy following bariatric surgery. To our knowledge, this is the first use of FreeStyle Libre in dumping syndrome in pregnancy following bariatric surgery with troublesome nocturnal hypoglycaemia.

Learning points:

  • Bariatric surgery represents the most effective treatment modality in cases of severe obesity. With increasing prevalence of obesity, more people are likely to undergo bariatric procedures, many of which are women of childbearing age.

  • Fertility generally improves after bariatric surgery due to weight reduction, but pregnancy is not recommended for at least 12–24 months after surgery. If pregnancy occurs, there are currently little evidence-based guidelines available on how to manage complications such as dumping syndromes or gestational diabetes (GDM) in women with history of bariatric surgery.

  • Diagnosis of GDM relies on the use of a 75 g oral glucose tolerance test (OGTT). The use of this test in pregnant women is not recommended due to its potential to precipitate dumping syndrome. Capillary glucose monitoring profiles or continuous glucose monitoring (CGM) is being currently discussed as alternative testing modalities.

  • As the CGM technology becomes more available, including the recently introduced FreeStyle Libre Flash glucose monitoring system, more pregnant women, including those after bariatric surgery, will have access to this technology. We suggest urgent development of guidelines regarding the use of CGM and flash glucose monitoring tools in these circumstances and in the interim recommend careful consideration of their use on a case-to-case basis.

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Asma Deeb Paediatric Endocrinology Department, Mafraq Hospital, Abu Dhabi, United Arab Emirates

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Faisal Al-Zidgali Neonatology Department, Corniche Hospital, Abu Dhabi, United Arab Emirates

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Bibian N Ofoegbu Neonatology Department, Corniche Hospital, Abu Dhabi, United Arab Emirates

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Summary

Wolcott–Rallison syndrome (WRS) is a rare autosomal recessive disorder due to mutations in the EIF2AK3 gene. It is characterized by permanent neonatal diabetes mellitus, skeletal dysplasia, liver impairment, neutropenia and renal dysfunction. Liver is the most commonly affected organ and liver failure is the commonest cause of death in this syndrome. The EIF2AK3 gene encodes a transmembrane protein PERK, which is important for the cellular response to endoplasmic reticulum (ER) stress. The absence of PERK activity reduces the ER’s abilities to deal with stress, leading to cell death by apoptosis. On acquiring febrile illness, affected patients suffer from liver injury, which may progress into liver failure and death. Renal involvement is less common and is mainly in the form of functional renal impairment at the advanced stage of the disease. Structural renal anomalies have not been reported in WRS. We report a 6-month-old girl who presented with neonatal diabetes on day 1 of life. Her genetic testing confirmed WRS due to missense mutation in the EIF2AK3 gene (c.2867G > A, p.Gly956Glu). Parents are first-degree cousins and both are heterozygous carriers to the mutation. 2 paternal uncles had the same mutation and died of liver disease at 1 and 14 years of age. Neither had a renal disease. She presented with hematuria during a febrile illness at the age of 5 months. Ultrasound scan showed right ectopic multicystic dysplastic kidney (MCDK). To the best of our knowledge, this is the first patient with WRS who is reported to have an MCDK disease.

Learning points:

  • Neonatal diabetes should be considered in babies presenting with early hyperglycemia particularly if there is a family history.

  • Genetic diagnosis in neonatal diabetes enables disease confirmation, genetic counseling and anticipation of potential complications during concomitant situations such as acute illness, trauma or major surgery.

  • There is lack of phenotype–genotype correlation in Wolcott–Rallison syndrome.

  • Structural kidney abnormality, in our case MCDK, can be seen in WRS.

Open access