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Hakan Ozoran Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
Clinical Medical School, University of Oxford, Oxford, UK
Green Templeton College, University of Oxford, Oxford, UK

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Phoenix Guwa Clinical Medical School, University of Oxford, Oxford, UK
Green Templeton College, University of Oxford, Oxford, UK

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Pam Dyson Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

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Garry D Tan Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals Foundation Trust, Oxford, UK
NIHR Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK

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Fredrik Karpe Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
NIHR Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK

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Summary

The use of a low-carbohydrate diet (LCD) reduces insulin requirements in insulinopenic states such as type 1 diabetes mellitus (T1DM). However, the use of potentially ketogenic diets in this clinical setting is contentious and the mechanisms underlying their impact on glycaemic control are poorly understood. We report a case of a patient with a late-onset classic presentation of T1DM who adopted a very low-carbohydrate diet and completely avoided insulin therapy for 18 months, followed by tight glycaemic control on minimal insulin doses. The observations suggest that adherence to an LCD in T1DM, implemented soon after diagnosis, can facilitate an improved and less variable glycaemic profile in conjunction with temporary remission in some individuals. Importantly, these changes occurred in a manner that did not lead to a significant increase in blood ketone (beta-hydroxybutyrate) concentrations. This case highlights the need for further research in the form of randomised controlled trials to assess the long-term safety and sustainability of carbohydrate-reduced diets in T1DM.

Learning points

  • This case highlights the potential of low-carbohydrate diets (LCDs) in type 1 diabetes mellitus (T1DM) to mediate improved diabetes control and possible remission soon after diagnosis.

  • Could carbohydrate-reduced diets implemented early in the course of T1DM delay the decline in endogenous insulin production?

  • Adherence to an LCD in T1DM can facilitate an improved and less variable glycaemic profile.

  • This case suggests that LCDs in T1DM may not be associated with a concerning supraphysiological ketonaemia.

Open access
Anne Cathrine Parelius Wammer Department of Endocrinology, Akershus University Hospital, Lørenskog, Norway

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Ingrid Nermoen Department of Endocrinology, Akershus University Hospital, Lørenskog, Norway
Institute of Clinical Medicine, University of Oslo, Oslo, Norway

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Per Medbøe Thorsby Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Hormone Laboratory, Department of Medical Biochemistry and Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Norway

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Nils Bolstad Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway

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Kari Lima Department of Endocrinology, Akershus University Hospital, Lørenskog, Norway

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Hoa Tran Department of Haematology, Akershus University Hospital, Lørenskog, Norway

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Ivar Følling Department of Endocrinology, Akershus University Hospital, Lørenskog, Norway
Institute of Clinical Medicine, University of Oslo, Oslo, Norway

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Summary

We present a young woman with treatment resistant insulin autoimmune syndrome (IAS) with a protracted course. Her serum insulin level was 6945 pmol/l (<160), C-peptide 4042 pmol/L (<1480), anti-insulin antibodies 5305 U/mL (<0.4) were monoclonal IgG kappa. After 12 h of fasting, her blood glucose fell to 1.2 mmol/L. Post-meal blood glucose peaked at 12.2 mmol/L with reactive hypoglycaemia below 2 mmol/L. Frequent meals and continuous blood glucose monitoring were helpful, but further treatments advocated in the literature with prednisolone, rituximab, plasmapheresis, cyclophosphamide and ciclosporin were without beneficial effect.

Based on this case and a review of the literature, we propose that IAS is not one but two different diseases with different therapeutic strategies. The first disease, polyclonal IAS, predominates in Asia and is characterized by polyclonal anti-insulin antibodies, association with certain HLA genotypes and other autoimmune conditions, medications and viral infections possibly triggering the disease, a possible female predominance among young patients and a tendency towards spontaneous remission. The other disease, monoclonal IAS, predominates in Caucasians. Typical features are monoclonal anti-insulin antibodies, only weak HLA association, no drug predisposition, no sex difference, rare remission and conventional therapy often being without any clinical effect. We suggest that monoclonal IAS with IgG or IgA anti-insulin antibodies should receive therapy targeting plasma cells rather than lymphocytes.

Learning points

  • IAS may be considered as two separate diseases, polyclonal and monoclonal.

  • The presence of either polyclonal or monoclonal antibodies should determine the choice of treatment for IAS.

  • In polyclonal IAS, discontinuation of a triggering medication and treatment of triggering conditions should be the backbone of therapy.

  • Monoclonal IAS should receive treatment targeting plasma cells.

Open access
Rikako Nakajima Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Hiroto Idesawa Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Daisuke Sato Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Jun Ito Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Kei Ito Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Masanao Fujii Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Takamichi Suzuki Department of Gastrointestinal Surgery, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Tomoaki Furuta Department of Gastrointestinal Surgery, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Hitomi Kawai Department of Pathology, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Norio Takayashiki Department of Pathology, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Masanao Kurata Department of Gastrointestinal Surgery, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Hiroaki Yagyu Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

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Summary

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery.

Learning points

  • Insulinoma occasionally leads to postprandial hypoglycemia.

  • The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection.

  • The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Open access
Motohiro Sekiya Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Mikiko Yuhara Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Yuki Murayama Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Mariko Ohyama Osawa Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Rikako Nakajima Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Nami Ohuchi Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Nako Matsumoto Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Daichi Yamazaki Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Sayuri Mori Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Takaaki Matsuda Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Yoko Sugano Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Yoshinori Osaki Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Hitoshi Iwasaki Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Hiroaki Suzuki Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Hitoshi Shimano Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan

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Summary

A paired homeodomain transcription factor, PAX6 (paired-box 6), is essential for the development and differentiation of pancreatic endocrine cells as well as ocular cells. Despite the impairment of insulin secretion observed in PAX6-deficient mice, evidence implicating causal association between PAX6 gene mutations and monogenic forms of human diabetes is limited. We herein describe a 33-year-old Japanese woman with congenital aniridia who was referred to our hospital because of her uncontrolled diabetes with elevated hemoglobin A1c (13.1%) and blood glucose (32.5 mmol/L) levels. Our biochemical analysis revealed that her insulin secretory capacity was modestly impaired as represented by decreased 24-h urinary C-peptide levels (38.0 μg/day), primarily explaining her diabetes. Intriguingly, there was a trend toward a reduction in her serum glucagon levels as well. Based on the well-recognized association of PAX6 gene mutations with congenital aniridia, we screened the whole PAX6 coding sequence, leading to an identification of a heterozygous Gln135* mutation. We tested our idea that this mutation may at least in part explain the impaired insulin secretion observed in this patient. In cultured pancreatic β-cells, exogenous expression of the PAX6 Gln135* mutant produced a truncated protein that lacked the transcriptional activity to induce insulin gene expression. Our observation together with preceding reports support the recent attempt to include PAX6 in the growing list of genes causally responsible for monogenic diabetes. In addition, since most cases of congenital aniridia carry PAX6 mutations, we may need to pay more attention to blood glucose levels in these patients.

Learning points

  • PAX6 Gln135* mutation may be causally associated not only with congenital aniridia but also with diabetes.

  • Blood glucose levels may deserve more attention in cases of congenital aniridia with PAX6 mutations.

  • Our case supports the recent attempt to include PAX6 in the list of MODY genes, and Gln135* may be pathogenic.

Open access
Eimear Mary O’Donovan Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

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Begona Sanchez-Lechuga Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

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Emma Prehn Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

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Maria Michelle Byrne Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

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Summary

The coexistence of autoimmune diabetes and maturity-onset diabetes (MODY) is rare. The absence of pancreatic autoantibodies is a key factor prompting MODY genetic testing. In this study, we report three cases of young-onset diabetes with progressive beta-cell dysfunction, strongly positive glutamic acid decarboxylase (GAD) antibodies, and genetic confirmation of pathogenic gene variants of HNF-1A, HNF-4A, and ABCC8-MODY. The first case is a woman diagnosed with HNF-1A-MODY diabetes more than 30 years after her diagnosis of adult-onset diabetes at 25 years. She required insulin after her fourth pregnancy. She became ketotic on oral hypoglycaemic agents (OHAs) and subsequently, her GAD antibodies tested positive. The second case is a woman diagnosed with diabetes at 17 years who was subsequently diagnosed with HNF-4A-MODY after many hypoglycaemic episodes on low-dose insulin. GAD antibodies were strongly positive. The last case is a man diagnosed with diabetes at 26 years who was well controlled on OHAs and required insulin years later due to sudden deterioration in glycaemic control. His ABCC8-MODY was diagnosed upon realisation of strong family history and his GAD antibodies tested positive. All subjects are now treated with insulin. Less than 1% of subjects with MODY have positive autoantibodies. These cases highlight individuals who may have two different types of diabetes simultaneously or consecutively. Deterioration of glycaemic control in subjects with MODY diabetes should highlight the need to look for the emergence of autoantibodies. At each clinic visit, one should update the family history as MODY was diagnosed in each case after the development of diabetes in their offspring.

Learning points

  • These cases highlight the rare coexistence of autoimmune diabetes and MODY.

  • Deterioration of glycaemic control in subjects with MODY diabetes should highlight the emergence of autoantibodies.

  • One should revise and update the family history as the diagnosis of MODY was made after the development of diabetes in offspring.

  • Understanding the spectrum of diabetes allows for precision medicine.

Open access
Megha Verma Department of Pediatrics, Endocrinology and Diabetes, Washington University School of Medicine, St. Louis, Missouri, USA
Saint Louis University School of Medicine, St. Louis, Missouri, USA

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Stephen I Stone Department of Pediatrics, Endocrinology and Diabetes, Washington University School of Medicine, St. Louis, Missouri, USA

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Summary

We identified an adolescent young woman with new-onset diabetes. Due to suspicious family history, she underwent genetic testing for common monogenic diabetes (MODY) genes. We discovered that she and her father carry a novel variant of uncertain significance in the HNF1A gene. She was successfully transitioned from insulin to a sulfonylurea with excellent glycemic control. Based on her family history and successful response to sulfonylurea, we propose that this is a novel pathogenic variant in HNF1A. This case highlights the utility of genetic testing for MODY, which has the potential to help affected patients control their diabetes without insulin.

Learning points

  • HNF1A mutations are a common cause of monogenic diabetes in patients presenting with early-onset diabetes and significant family history.

  • Genetic testing in suspected patients allows for the identification of mutations causing monogenic diabetes.

  • First-degree relatives of the affected individual should be considered for genetic testing.

  • The use of sulfonylurea agents in patients with HNF1A-MODY can reduce dependence on insulin therapy and provide successful glycemic control.

Open access
Minna Koivikko Department of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland

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Tapani Ebeling Department of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland

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Markus Mäkinen Department of Pathology, University of Oulu, Oulu, Finland

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Juhani Leppäluoto Institute of Biomedicine, University of Oulu, Oulu, Finland

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Antti Raappana Department of Otorhinolaryngology, University of Oulu and Oulu University Hospital, Oulu, Finland

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Petteri Ahtiainen Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä, Finland

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Pasi Salmela Department of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland

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Summary

Multiple endocrine neoplasia type 1 NM_001370259.2(MEN1):c.466G>C(p.Gly156Arg) is characterized by tumors of various endocrine organs. We report on a rare, growth hormone-releasing hormone (GHRH)-releasing pancreatic tumor in a MEN1 patient with a long-term follow-up after surgery. A 22-year-old male with MEN1 syndrome, primary hyperparathyroidism and an acromegalic habitus was observed to have a pancreatic tumor on abdominal CT scanning, growth hormone (GH) and insulin-like growth factor 1 (IGF1) were elevated and plasma GHRH was exceptionally high. GHRH and GH were measured before the treatment and were followed during the study. During octreotide treatment, IGF1 normalized and the GH curve was near normal. After surgical treatment of primary hyperparathyroidism, a pancreatic tail tumor was enucleated. The tumor cells were positive for GHRH antibody staining. After the operation, acromegaly was cured as judged by laboratory tests. No reactivation of acromegaly has been seen during a 20-year follow-up. In conclusion, an ectopic GHRH-producing, pancreatic endocrine neoplasia may represent a rare manifestation of MEN1 syndrome.

Learning points

  • Clinical suspicion is in a key position in detecting acromegaly.

  • Remember genetic disorders with young individuals having primary hyperparathyroidism.

  • Consider multiple endocrine neoplasia type 1 syndrome when a person has several endocrine neoplasia.

  • Acromegaly may be of ectopic origin with patients showing no abnormalities in radiological imaging of the pituitary gland.

Open access
Ana Dugic Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Michael Kryk Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Claudia Mellenthin Department of Surgery, HFR Fribourg, Fribourg, Switzerland

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Christoph Braig Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Lorenzo Catanese Department for Nephrology, Angiology and Rheumatology, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Sandy Petermann Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Jürgen Kothmann Department for Nephrology, Angiology and Rheumatology, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Steffen Mühldorfer Department for Gastroenterology, Endocrinology and Metabolic Diseases, Bayreuth University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Bayreuth, Germany

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Summary

Drinking fruit juice is an increasingly popular health trend, as it is widely perceived as a source of vitamins and nutrients. However, high fructose load in fruit beverages can have harmful metabolic effects. When consumed in high amounts, fructose is linked with hypertriglyceridemia, fatty liver and insulin resistance. We present an unusual case of a patient with severe asymptomatic hypertriglyceridemia (triglycerides of 9182 mg/dL) and newly diagnosed type 2 diabetes mellitus, who reported a daily intake of 15 L of fruit juice over several weeks before presentation. The patient was referred to our emergency department with blood glucose of 527 mg/dL and glycated hemoglobin (HbA1c) of 17.3%. Interestingly, features of diabetic ketoacidosis or hyperosmolar hyperglycemic state were absent. The patient was overweight with an otherwise unremarkable physical exam. Lipase levels, liver function tests and inflammatory markers were closely monitored and remained unremarkable. The initial therapeutic approach included i.v. volume resuscitation, insulin and heparin. Additionally, plasmapheresis was performed to prevent potentially fatal complications of hypertriglyceridemia. The patient was counseled on balanced nutrition and detrimental effects of fruit beverages. He was discharged home 6 days after admission. At a 2-week follow-up visit, his triglyceride level was 419 mg/dL, total cholesterol was 221 mg/dL and HbA1c was 12.7%. The present case highlights the role of fructose overconsumption as a contributory factor for severe hypertriglyceridemia in a patient with newly diagnosed diabetes. We discuss metabolic effects of uncontrolled fructose ingestion, as well as the interplay of primary and secondary factors, in the pathogenesis of hypertriglyceridemia accompanied by diabetes.

Learning points

  • Excessive dietary fructose intake can exacerbate hypertriglyceridemia in patients with underlying type 2 diabetes mellitus (T2DM) and absence of diabetic ketoacidosis or hyperosmolar hyperglycemic state.

  • When consumed in large amounts, fructose is considered a highly lipogenic nutrient linked with postprandial hypertriglyceridemia and de novo hepatic lipogenesis (DNL).

  • Severe lipemia (triglyceride plasma level > 9000 mg/dL) could be asymptomatic and not necessarily complicated by acute pancreatitis, although lipase levels should be closely monitored.

  • Plasmapheresis is an effective adjunct treatment option for rapid lowering of high serum lipids, which is paramount to prevent acute complications of severe hypertriglyceridemia.

Open access
Marcio José Concepción-Zavaleta Division of Endocrinology, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru

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Sofía Pilar Ildefonso-Najarro Division of Endocrinology, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru

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Esteban Alberto Plasencia-Dueñas Division of Endocrinology, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru

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María Alejandra Quispe-Flores Division of Endocrinology, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru

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Cristian David Armas-Flórez School of Medicine, Universidad Nacional de Trujillo, Trujillo, Peru

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Laura Esther Luna-Victorio Division of Endocrinology, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru

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Summary

Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease caused by antibodies against the insulin receptor. It should be considered in patients with dysglycaemia and severe insulin resistance when other more common causes have been ruled out. We report a case of a 72-year-old male with a 4-year history of type 2 diabetes who presented with hypercatabolism, vitiligo, acanthosis nigricans, and hyperglycaemia resistant to massive doses of insulin (up to 1000 U/day). Detection of anti-insulin receptor antibodies confirmed TBIR. The patient received six pulses of methylprednisolone and daily treatment with cyclophosphamide for 6 months. Response to treatment was evident after the fourth pulse of methylprednisolone, as indicated by weight gain, decreased glycosylated haemoglobin and decreased requirement of exogenous insulin that was later discontinued due to episodes of hypoglycaemia. Remission was eventually achieved and the patient is currently asymptomatic, does not require insulin therapy, has normal glycaemia and is awaiting initiation of maintenance therapy with azathioprine. Thus, TBIR remitted without the use of rituximab. This case highlights the importance of diagnosis and treatment in a timely fashion, as well as the significance of clinical features, available laboratory findings and medication. Large controlled studies are required to standardise a therapeutic protocol, particularly in resource-constrained settings where access to rituximab is limited.

Learning points:

  • Type B insulin resistance syndrome is a rare autoimmune disorder that should be considered in patients with dysglycaemia, severe insulin resistance and a concomitant autoimmune disease.

  • Serological confirmation of antibodies against the insulin receptor is not necessary in all cases due to the high associated mortality without timely treatment.

  • Although there is no standardised immunosuppressive treatment, a protocol containing rituximab, cyclophosphamide and steroids has shown a significant reduction in previously reported mortality rates.

  • The present case, reports successful remission in an atypical patient using cyclophosphamide and methylprednisolone, which is an effective therapy in countries in which rituximab is not covered by health insurance.

  • When there is improvement in the hypercatabolic phase, the insulin dose should be reduced and/or discontinued to prevent hypoglycaemia; a mild postprandial hyperglycaemic state should be acceptable.

Open access
Yuki Fujita Center for Diabetes, Endocrinology & Metabolism, Kansai Electric Power Hospital, Osaka, Japan
Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan

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Daisuke Tanaka Department of Diabetes, Endocrinology and Clinical Nutrition, Graduate School ofMedicine, Kyoto University, Kyoto, Japan

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Hisato Tatsuoka Department of Diabetes, Endocrinology and Clinical Nutrition, Graduate School ofMedicine, Kyoto University, Kyoto, Japan

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Miho Matsubara Center for Diabetes, Endocrinology & Metabolism, Kansai Electric Power Hospital, Osaka, Japan
Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan

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Takanori Hyo Center for Diabetes, Endocrinology & Metabolism, Kansai Electric Power Hospital, Osaka, Japan

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Yoshiyuki Hamamoto Center for Diabetes, Endocrinology & Metabolism, Kansai Electric Power Hospital, Osaka, Japan
Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan

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Toshiyuki Komiya Center for Nephrology, Kansai Electric Power Hospital, Osaka, Japan
Division of Renal Disease and Blood Purification, Kansai Electric Power Medical Research Institute, Kobe, Japan

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Nobuya Inagaki Department of Diabetes, Endocrinology and Clinical Nutrition, Graduate School ofMedicine, Kyoto University, Kyoto, Japan

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Yutaka Seino Center for Diabetes, Endocrinology & Metabolism, Kansai Electric Power Hospital, Osaka, Japan
Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan

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Yuji Yamazaki Center for Diabetes, Endocrinology & Metabolism, Kansai Electric Power Hospital, Osaka, Japan
Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan

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Summary

Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes mellitus characterised by early onset and dominant inheritance. Delayed diagnosis or misdiagnosis as type 1 or type 2 diabetes mellitus is common. Definitive genetic diagnosis is essential for appropriate treatment of patients with MODY. The hepatocyte nuclear factor 1-beta (HNF1B) gene is responsible for MODY type 5 (MODY5), which has distinctive clinical features including renal disease. MODY5 should always be considered by clinicians in patients with early onset diabetes and renal anomalies. We report a case of a 30-year-old Japanese male with early-onset diabetes mellitus, renal anomalies and family history of diabetes that was suggestive of MODY5. Renal histology showed no evidence of diabetic nephropathy. Genetic testing revealed a novel heterozygous splice-site mutation of the HNF1B gene in the family members. It was strongly suggested that the mutation could underlie our patient’s MODY5.

Learning points:

  • Genetic diagnosis of MODY is relevant for appropriate treatment.

  • Dominantly inherited early-onset diabetes mellitus with renal cysts suggests MODY5.

  • Scanning the non-coding regions is important for not missing a mutation in HNF1B.

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