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Summary
Familial renal glucosuria (FRG) is a rare renal tubular disorder characterized by increased urinary glucose excretion despite normoglycemia. It is most commonly caused by pathogenic variants in the solute carrier family V member 2 (SLC5A2) gene. This gene encodes the sodium–glucose cotransporter 2, crucial for glucose reabsorption. We report the case of a 44-year-old male referred to the endocrinology outpatient clinic for unexplained glucosuria despite well-controlled diabetes mellitus with metformin and gliclazide therapy. His main complaints were nocturia and an unintentional 5 kg weight loss in 1 year. A 24-h urinary collection revealed overt glucosuria (23.3 g/1.73 m2/24 h), generalized aminoaciduria, and increased uric acid excretion (fractional excretion: 6.4%). Whole-exome sequencing revealed a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene. Specific analysis of the maturity-onset diabetes of the young type (MODY) gene panel showed no pathogenic variants in the hepatocyte nuclear factor-1A (HNF-1A; MODY3) nor in other MODY-associated genes. We assume that the association of glucosuria, aminoaciduria, and increased uric acid excretion can be explained by the combination of diabetes and the likely pathogenic SLC5A2 variant in this patient. In conclusion, we describe a well-controlled diabetic patient with FRG, associated with a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene.
Learning points
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The diagnosis of a renal tubular disorder should be considered in patients with unexplained glucosuria and diabetes mellitus, especially if the latter is well controlled.
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FRG usually presents with glucosuria but may be associated with generalized aminoaciduria and hyperuricosuria.
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Genetic analysis should be considered in patients with young-onset diabetes and glucosuria, particularly with a positive family history.
Search for other papers by Ishara Ranathunga in
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Search for other papers by Chandima Idampitiya in
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Summary
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the destruction of the pancreatic beta cells, which produce insulin. Individuals with T1DM usually require at least 3-5 years to develop microvascular complications in comparison to people with type 2 diabetes (T2DM), who may develop complications even before the diagnosis of diabetes. We discuss a patient who presented with proliferative diabetic retinopathy subsequently diagnosed with T1DM and diabetic neuropathy following investigations. Diabetic retinopathy or other microvascular complications as the presenting feature of T1DM is rarely known or reported in the literature. A 33-year-old healthcare worker had been seen by the opticians due to 1-week history of blurred vision. The ophthalmology assessment had confirmed proliferative retinopathy in the right eye and severe non-proliferative retinopathy in the left eye with bilateral clinically significant macular oedema. His BMI was 24.9 kg/m2. The nervous system examination revealed bilateral stocking type peripheral neuropathy. The random venous glucose was 24.9 mmol/L. Plasma ketones were 0.7 mmol/L and HbA1c was 137 mmol/mol. On further evaluation, the anti-glutamic acid decarboxylase (GAD) antibody was positive, confirming the diagnosis of T1DM. He was started on aflibercept injections in both eyes, followed by panretinal photocoagulation. Subsequent nerve conduction studies confirmed the presence of symmetrical polyneuropathy. The pathogenesis of the development of microvascular complications in T1DM is multifactorial. Usually, the development of complications is seen at least a few years following the diagnosis. The occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important in preventing the progression of the disease.
Learning points
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The pathogenesis of the development of microvascular complications in type 1 diabetes mellitus is multifactorial.
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The development of complications is seen at least a few years following the diagnosis.
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Occurrence of microvascular complications at presentation is rare.
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This makes the management challenging and extremely important to prevent the progression of the disease.
Search for other papers by Joanna Chrzanowska in
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Search for other papers by Barbara Salmonowicz in
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Search for other papers by Agnieszka Zubkiewicz-Kucharska in
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Summary
The etiology of foot drop is diverse from various diseases to mechanic injuries and includes neuropathy of the peroneal nerve. Peroneal neuropathy might also be one of the forms of diabetic neuropathy, very rarely reported as the first sign of diabetes. We describe three cases of children with newly diagnosed type 1 diabetes (TID) who developed unilateral peroneal nerve palsies and tibial nerve palsies, presenting clinically as a foot drop. In two of our cases, the symptoms of foot drop occurred shortly after starting treatment for severe diabetes ketoacidosis. In the third patient, food drop was a reason for the initial medical consultation, but eventually, TID was diagnosed. The presented cases highlight that neuropathy can be observed not only as a chronic complication of T1D, but it can also appear at the time of disease manifestation. The incorrect position of the lower limb during a keto coma may contribute to the development of neuropathy.
Learning points
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Neuropathy can be observed not only as a chronic complication of type 1 diabetes (T1D), but it can also appear at the time of disease manifestation.
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The incorrect position of the lower limb causing external pressure during a keto coma may contribute to the development of neuropathy.
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It is important to examine the glycemia in patients with acute peroneal neuropathy, as this kind of peripheral neuropathy can be associated with newly diagnosed T1D. Normalization of glycemia might lead to rapid neuronal recovery.
Clinic for Pediatrics and Adolescent Medicine/Metabolism Laboratory, Universitätsklinikum Münster, Münster, Germany
Search for other papers by Clemens Gardemann in
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Search for other papers by Thorsten Marquardt in
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Summary
Traditional guidelines for type 1 diabetics do not restrict carbohydrates to improve clinical outcomes for patients. This paper highlights the favorable blood glucose control outcomes when a type 1 diabetic focuses on caloric intake from protein and healthy fats instead of the traditional carbohydrate-focused meals. We followed a male type 1 diabetic in his 20s adopting a ketogenic diet through a process of slowly lowering total daily carbohydrate intake. Diabetes-related biomarkers were measured throughout the process. Diabetes-related biomarkers saw massive improvements and ended up in the official non-diabetic range. Total daily insulin requirements dropped by 70%. The patient also experienced great improvements in his quality of life. This study demonstrates the possibility of improving diabetes-related biomarkers through dietary changes, which have positive effects on health outcomes in patients living with this disease.
Learning points
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The adaptation of a ketogenic diet improved diabetes-related biomarkers in this patient.
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Diabetes-related biomarkers, such as HbA1c, are the main risk factors for developing complications in diabetics.
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The ketogenic diet is a feasible approach to minimizing the risk of developing complications in diabetics.
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Total daily insulin requirements dropped by 67% adapting a ketogenic diet.
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The patient experienced enormous changes in the quality of life after adapting to the new diet.
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The safe and physiological state of ketosis might be associated with additional benefits for the patient
Search for other papers by Osamu Horikawa in
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Department of Medicine, Omihachiman Community Medical Center, Omihachiman, Shiga, Japan
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Search for other papers by Hiroshi Maegawa in
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Summary
A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 μU/mL; 60 min: 953 μU/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother’s diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years.
Learning points
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Type A insulin resistance syndrome is caused by mutations in the insulin receptor (INSR) gene and results in severe insulin resistance.
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Genetic evaluation should be considered in adolescents or young adults with dysglycemia when an atypical phenotype, such as severe insulin resistance, or a relevant family history is observed.
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Clinical courses may differ even if the same genetic mutation is found in a family.
Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medicine, Takaramachi, Kanazawa, Japan
Department of Health Promotion and Medicine of the Future, Kanazawa University, Takaramachi, Kanazawa, Japan
Search for other papers by Toshitaka Sawamura in
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Search for other papers by Shigehiro Karashima in
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Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medicine, Takaramachi, Kanazawa, Japan
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Department of Health Promotion and Medicine of the Future, Kanazawa University, Takaramachi, Kanazawa, Japan
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Department of Health Promotion and Medicine of the Future, Kanazawa University, Takaramachi, Kanazawa, Japan
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Search for other papers by Yoshiyu Takeda in
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Department of Health Promotion and Medicine of the Future, Kanazawa University, Takaramachi, Kanazawa, Japan
Search for other papers by Takashi Yoneda in
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Summary
Fulminant type 1 diabetes (FT1D) is a subtype of diabetes characterized by rapid progression of β-cell destruction, hyperglycemia, and diabetic ketoacidosis (DKA). The pathogenesis of this disease remains unclear. However, viral infections, HLA genes, and immune checkpoint inhibitor use were reportedly involved in this disease. A 51-year-old Japanese man with no chronic medical condition was admitted to our hospital with complaints of nausea and vomiting. Cough, sore throat, nasal discharge, and diarrhea were not noted. He had a medical history of at least two influenza infections. His vaccination history was notable for receiving an inactive split influenza vaccine 12 days prior to developing these symptoms. He was diagnosed with DKA associated with FT1D. His HLA class II genotypes were nonsusceptible to FT1D, and he had a negative history of immune checkpoint inhibitor use. The destruction of the pancreas by cytotoxic T cells is reported to be involved in FT1D. Inactive split influenza vaccines do not directly activate cytotoxic T cells. However, these could activate the redifferentiation of memory CD8-positive T cells into cytotoxic T cells and induce FT1D, as this patient had a history of influenza infections.
Learning points
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Influenza split vaccination could cause fulminant type 1 diabetes (FT1D).
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The mechanism of influenza split vaccine-induced FT1D might be through the redifferentiation of CD8-positive memory T cells into cytotoxic T cells.
Search for other papers by Micah A Fischer in
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Search for other papers by Salaheddin H Elrokhsi in
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Summary
Multiple research studies address the anti-insulinemic effect of growth hormone (GH). We report a case of a patient with anterior hypopituitarism on GH replacement who later developed type 1 diabetes mellitus (T1DM). Recombinant human growth hormone (rhGH) therapy was discontinued at the time of growth completion. Because of significantly improved glycemic control, this patient was weaned off subcutaneous insulin. He regressed from stage 3 to stage 2 T1DM and remained in this status for at least 2 years and until the writing of this paper. The diagnosis of T1DM was established based on relatively low C-peptide and insulin levels for the degree of hyperglycemia as well as seropositivity of zinc transporter antibody and islet antigen-2 antibody. Additional laboratory data obtained 2 months after discontinuing rhGH revealed improved endogenous insulin secretion. This case report calls attention to the diabetogenic effect of GH therapy in the setting of T1DM. It also demonstrates the possibility of regression from stage 3 T1DM requiring insulin therapy to stage 2 T1DM with asymptomatic dysglycemia after discontinuing rhGH.
Learning points
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Given the diabetogenic effect of growth hormone, blood glucose levels should be monitored in patients with type 1 diabetes mellitus (T1DM) on insulin therapy and recombinant human growth hormone (rhGH) replacement.
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Clinicians should closely monitor for risk of hypoglycemia after discontinuing rhGH among T1DM patients who are on insulin treatment.
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The discontinuation of rhGH in the setting of T1DM may cause regression of symptomatic T1DM to asymptomatic dysglycemia requiring no insulin treatment.
Search for other papers by Valerie Lai in
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Division of Endocrinology and Metabolism, University of Alberta, Edmonton, AB, Canada
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Search for other papers by Shailly Jain-Ghai in
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Summary
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency is an inborn error of metabolism resulting in a lack of ketogenesis and leucine catabolism. Hallmarks of decompensation include hypoglycemia without ketosis (or hypoketosis), metabolic acidosis, and hyperammonemia. Management includes avoiding fasting and restricting dietary protein and fat. Conversely, type 2 diabetes mellitus (T2DM) requires carbohydrate restriction and/or anti-hyperglycemic agents; thus, managing these co-existing disorders is challenging. A 36-year-old male with HMG-CoA lyase deficiency and T2DM (Hemoglobin A1c (HbA1c): 7.9%) presented with confusion and shock. Blood work revealed metabolic acidosis, hyperammonemia, hyperglycemia, and hypoketosis. The patient was diagnosed with hyperosmolar non-ketotic hyperglycemia and hyperammonemia secondary to HMG-CoA lyase metabolic decompensation requiring intensive care unit admission. Hyperammonemia management was challenging because alternative calories with i.v. dextrose (due to hyperglycemia) and i.v. lipids (due to HMG-CoA lyase deficiency) could not be provided as usual. The patient was started on hemodialysis and i.v. insulin with marked improvement. Once stabilized, metformin and insulin were initiated. T2DM impaired cellular glucose uptake and produced a state similar to hypoglycemia, despite the patient being profoundly hyperglycemic, which led to metabolic decompensation of HMG-CoA lyase deficiency. Managing T2DM and HMG-CoA lyase deficiency warrants special considerations due to the potential for metabolic decompensation with both hyperglycemia and hypoglycemia.
Learning points
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In a patient with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency and type 2 diabetes mellitus (T2DM), management principles include avoiding hypoglycemia to prevent metabolic decompensation, providing insulin for proper glucose utilization, and moderation of carbohydrate intake to prevent consequences of chronic hyperglycemia.
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The development of insulin resistance in the form of T2DM in HMG-CoA lyase deficiency likely triggered a state similar to hypoglycemia, leading to cellular energy deficiency and subsequently metabolic decompensation.
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It is important to avoid hypoglycemia in patients with HMG-CoA lyase deficiency and T2DM, as the risk of metabolic decompensation is increased due to the lack of ketogenesis in HMG-CoA lyase deficiency.
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Selection of antidiabetic agents in this patient population requires careful consideration, and agents that have a higher risk of hypoglycemia should be avoided.
College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia
Search for other papers by Raad Alwithenani in
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Search for other papers by Danielle M Andrade in
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Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
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Search for other papers by Karen E Gomez-Hernandez in
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Summary
Myopathy caused by thyrotoxicosis is not uncommon. Skeletal muscles are commonly involved, but dysphagia is a rare manifestation of thyrotoxicosis. We aim to raise awareness of dysphagia caused by hyperthyroidism and review similar cases in the literature. We present a case of severe dysphagia caused by hyperthyroidism. We also summarize similar case reports in the literature. Our patient is a 77-year-old man who presented with thyrotoxicosis related to Graves’ disease (GD), dysphagia to both liquid and solid food, and weight loss. Further investigations revealed severe esophageal dysphagia and a high risk for aspiration. He required the placement of a G-tube for feeding. After 8 weeks of methimazole treatment, his thyroid function normalized and his dysphagia improved significantly, leading to the removal of the feeding G-tube. We summarize 19 case reports published in the literature of hyperthyroidism leading to dysphagia. Patients with thyrotoxicosis and dysphagia are at higher risk for aspiration pneumonia and thyroid storm. Based on previous case reports, on average, approximately 3 weeks of treatment with anti-thyroidal drugs and beta-blockers is needed before patients can eat normally. We report a case of dysphagia associated with GD, which is rare and needs prompt recognition to restore euthyroid status. Dysphagia generally resolved with normalization of thyroid function.
Learning points
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Myopathy caused by thyrotoxicosis is not uncommon.
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Skeletal muscles are commonly involved, but dysphagia is a rare manifestation of thyrotoxicosis.
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Dysphagia due to hyperthyroidism resolves with normalization of thyroid function.
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Early recognition of dysphagia related to hyperthyroidism and early initiation of therapy may help reverse the dysphagia and prevent complications.
Search for other papers by George Brown in
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Summary
Vasoactive intestinal peptide-secreting tumours (VIPomas) are an extremely rare form of functional pancreatic neuroendocrine tumour with an estimated annual incidence of 1 in 10 million. Associated tumour hypersecretion of other peptides, including pancreatic polypeptide (PPomas), may also be seen. These malignancies classically present with a defined triad of refractory diarrhoea, hypokalaemia and metabolic acidosis known as Verner–Morrison syndrome. Diagnosis is frequently delayed, and the majority of patients will have metastatic disease at presentation. Symptoms are usually well controlled with somatostatin analogue administration. Here we report a case of metastatic mixed VIPoma/PPoma-induced diarrhoea causing renal failure so severe that ultrafiltration was required to recover adequate renal function.
Learning points
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Profuse, watery diarrhoea is a common presenting complaint with a multitude of aetiologies. This, combined with the rarity of these tumours, makes diagnosis difficult and frequently delayed. A functional neuroendocrine tumour should be suspected when diarrhoea is unusually extreme, prolonged and common causes have been promptly excluded.
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These patients are likely to be profoundly unwell on presentation. They are extremely hypovolaemic with dangerous electrolyte and metabolic abnormalities. Aggressive initial rehydration and electrolyte replacement are imperative. A somatostatin analogue should be commenced as soon as the diagnosis is suspected.
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This is an extreme example of Verner–Morrison syndrome. We are unaware of another case where renal failure secondary to diarrhoea and dehydration was so severe that renal replacement therapy was required to restore adequate renal function, further emphasising how critically unwell these patients can be.
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Both the primary tumour and metastases showed a remarkably good and rapid response to somatostatin analogue administration. Cystic change and involution were noted on repeat imaging within days.
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Prior to his illness, this patient was extremely high functioning with no medical history. His diagnosis was an enormous psychological shock, and the consideration and care for his psychological well-being were a crucial part of his overall management. It highlights the importance of a holistic approach to cancer care and the role of the clinical nurse specialist within the cancer multidisciplinary team.
