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1.
Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: a case report and literature review.
Gauci, ML, Laly, P, Vidal-Trecan, T, Baroudjian, B, Gottlieb, J, Madjlessi-Ezra, N, Da Meda, L, Madelaine-Chambrin, I, Bagot, M, Basset-Seguin, N, et al
Cancer immunology, immunotherapy : CII. 2017;(11):1399-1410
Abstract
Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis. Nivolumab was withheld 3.5 weeks and insulin therapy was initiated, enabling a normalization of glycaemia and the disappearance of symptoms. Laboratory investigations demonstrated the presence of islet cell autoantibodies, while C-peptide was undetectable. Retrospective explorations on serum banked at week 0 and 3 months before the start of nivolumab, already showed the presence of autoantibodies, but normal insulin, C-peptide secretion and glycaemia. Partial response was obtained at month 3, and nivolumab was then resumed at the same dose. The clinical context and biological investigations before, at and after nivolumab initiation suggest the autoimmune origin of this diabetes, most likely induced by anti-PD-1 antibody in a predisposed patient. The role of PD-1/PD-L1 binding is well known in the pathogenesis of type 1 diabetes. Therefore, this rare side effect can be expected in a context of anti-PD-1 treatment. Glycaemia should be monitored during PD-1/PD-L1 blockade. The presence of autoantibodies before treatment could identify individuals at risk of developing diabetes, but systematic titration may not be relevant considering the rarity of this side effect.
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2.
Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature.
Hickmott, L, De La Peña, H, Turner, H, Ahmed, F, Protheroe, A, Grossman, A, Gupta, A
Targeted oncology. 2017;(2):235-241
Abstract
Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.
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3.
Generalized Status Epilepticus in a Patient with Acute-onset Type 1 Diabetes Mellitus Associated with Severe Kidney Dysfunction: A Case Report and Literature Review.
Ohara, N, Koda, R, Watanabe, H, Iino, N, Ohashi, K, Terajima, K, Ozawa, T, Ikeda, Y, Sekiguchi, H, Ohashi, H, et al
Internal medicine (Tokyo, Japan). 2017;(15):1993-1999
Abstract
A 65-year-old Japanese man with advanced chronic kidney disease (CKD) developed acute-onset type 1 diabetes mellitus (T1D) that was associated with severe acute kidney injury and was manifested by generalized tonic-clonic status epilepticus. His seizures resolved without recurrence after correcting the diabetic ketoacidosis. Although hyperglycemia is an important cause of acute symptomatic seizure (ASS), patients with ketotic hyperglycemia develop ASS less frequently. In this T1D case with CKD, severe hyperglycemia in conjunction with other metabolic insults, such as uremia, hyponatremia, and hypocalcemia, probably provoked his seizure despite the severe ketonemia.
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4.
Combination high-dose omega-3 fatty acids and high-dose cholecalciferol in new onset type 1 diabetes: a potential role in preservation of beta-cell mass.
Baidal, DA, Ricordi, C, Garcia-Contreras, M, Sonnino, A, Fabbri, A
European review for medical and pharmacological sciences. 2016;(15):3313-8
Abstract
Several studies have evaluated the role of inflammation in type 1 diabetes (T1D). The safety profile and anti-inflammatory properties of high dose omega-3 fatty acids combined with Vitamin D supplementation make this therapy a possible candidate for T1D intervention trials. Herein, we describe the case of a 14-year-old boy with new onset T1D treated with high dose Omega-3 and vitamin D3. By 12 months, peak C-peptide increased to 0.55 nmol/L (1.66 ng/mL) corresponding to a 20% increment from baseline and AUC C-peptide was slightly higher compared to 9 months (0.33 vs. 0.30 nmol/L/min) although remaining slightly lower than baseline. Combination high-dose Omega-3 fatty acids and high-dose vitamin D3 therapy was well tolerated and may have beneficial effects on beta-cell function. Randomized controlled trials could be of assistance to determine whether this therapy may result in the preservation of beta-cell function in patients with new onset T1D.
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5.
The development of fulminant type 1 diabetes during chemotherapy for rectal cancer.
Adachi, J, Mimura, M, Gotyo, N, Watanabe, T
Internal medicine (Tokyo, Japan). 2015;(7):819-22
Abstract
A 34-year-old man with a history of rectal cancer was receiving oral chemotherapy [tegafur-uracil (UFT) with leucovorin]. He visited our hospital due to nausea and abdominal pain, and his laboratory data revealed the presence of urinary ketones, hyperglycemia and high anion gap metabolic acidosis, and HbA1c level of 6.8%. Accordingly, we diagnosed fulminant type 1 diabetes. The development of fulminant type 1 diabetes during chemotherapy for malignancy is a rare, but potentially fatal condition. Therefore, clinicians should consider diabetic ketoacidosis in the differential diagnosis when examining chemotherapy patients who present with gastrointestinal symptoms.
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6.
Aceruloplasminemia presents as Type 1 diabetes in non-obese adults: a detailed case series.
Vroegindeweij, LH, van der Beek, EH, Boon, AJ, Hoogendoorn, M, Kievit, JA, Wilson, JH, Langendonk, JG
Diabetic medicine : a journal of the British Diabetic Association. 2015;(8):993-1000
Abstract
AIM: To detect features that might lead to the early diagnosis and treatment of aceruloplasminemia, as initiation of treatment before the onset of neurological symptoms is likely to prevent neurological deterioration. METHODS The PubMed and OMIM databases were searched for published cases of aceruloplasminemia. Diagnostic criteria for aceruloplasminemia were undetectable or very low serum ceruloplasmin, hyperferritinemia and low transferrin saturation. Clinical, biochemical and radiological data on the presentation and follow-up of the cases were extracted and completed through e-mail contact with all authors. RESULTS We present an overview of 55 aceruloplasminemia cases, including three previously unreported cases. Diabetes mellitus was the first symptom related to aceruloplasminemia in 68.5% of the patients, manifesting at a median age of 38.5 years, and often accompanied by microcytic or normocytic anaemia. The combination preceded neurological symptoms in almost 90% of the neurologically symptomatic patients and was found 12.5 years before the onset of neurological symptoms. CONCLUSIONS There is a diagnostic window during which diabetes and anaemia are present although there is an absence of neurological symptoms. Screening for aceruloplasminemia in adult non-obese individuals presenting with antibody-negative, insulin-dependent diabetes mellitus and unexplained anaemia is recommended. The combination of ferritin and transferrin saturation provides a sensitive initial measure for aceruloplasminemia.
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7.
Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal small fibre neuropathy.
Tran, C, Philippe, J, Ochsner, F, Kuntzer, T, Truffert, A
Swiss medical weekly. 2015;:w14131
Abstract
INTRODUCTION Acute painful diabetic neuropathy (APDN) is a distinctive diabetic polyneuropathy and consists of two subtypes: treatment-induced neuropathy (TIN) and diabetic neuropathic cachexia (DNC). The characteristics of APDN are (1.) the small-fibre involvement, (2.) occurrence paradoxically after short-term achievement of good glycaemia control, (3.) intense pain sensation and (4.) eventual recovery. In the face of current recommendations to achieve quickly glycaemic targets, it appears necessary to recognise and understand this neuropathy. METHODS AND RESULTS Over 2009 to 2012, we reported four cases of APDN. Four patients (three males and one female) were identified and had a mean age at onset of TIN of 47.7 years (±6.99 years). Mean baseline HbA1c was 14.2% (±1.42) and 7.0% (±3.60) after treatment. Mean estimated time to correct HbA1c was 4.5 months (±3.82 months). Three patients presented with a mean time to symptom resolution of 12.7 months (±1.15 months). One patient had an initial normal electroneuromyogram (ENMG) despite the presence of neuropathic symptoms, and a second abnormal ENMG showing axonal and myelin neuropathy. One patient had a peroneal nerve biopsy showing loss of large myelinated fibres as well as unmyelinated fibres, and signs of microangiopathy. CONCLUSIONS According to the current recommendations of promptly achieving glycaemic targets, it appears necessary to recognise and understand this neuropathy. Based on our observations and data from the literature we propose an algorithmic approach for differential diagnosis and therapeutic management of APDN patients.
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8.
Disseminated mucormycosis in an adolescent with newly diagnosed diabetes mellitus.
McCrory, MC, Moore, BA, Nakagawa, TA, Givner, LB, Jason, DR, Palavecino, EL, Ajizian, SJ
The Pediatric infectious disease journal. 2014;(10):1094-6
Abstract
We report a 16-year-old, previously healthy female who presented with disseminated mucormycosis leading to multiorgan failure and death with newly diagnosed type 1 diabetes mellitus and ketoacidosis. We review previous reported cases of mucormycosis in children with diabetes to demonstrate that this uncommon invasive infection may cause significant morbidity and mortality in this population.
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9.
Atypical neurologic presentations of new onset type 1 diabetes mellitus in pediatric age group: a report of five unusual cases and review of the literature.
Mulder, L, Onur, O, Kleis, L, Borders, H, Cemeroglu, AP
Journal of pediatric endocrinology & metabolism : JPEM. 2014;(7-8):749-56
Abstract
Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in childhood and is caused by insulin deficiency resulting from the autoimmune destruction of insulin producing beta cells of the pancreas. Most children in the US with new onset T1DM present with the classic signs and symptoms of hyperglycemia and 30% with diabetic ketoacidosis (DKA). Neurologic manifestations are relatively rare and mostly include lethargy, decreased level of consciousness, and coma as a result of DKA. In this article, five cases of new onset T1DM with exceedingly rare or unreported neurologic manifestations in the pediatric age group are presented, along with a review of the literature.
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10.
A child with altered sensorium, hyperglycemia, and elevated troponins.
Arora, R, Chiwane, S, Hartwig, E, Kannikeswaran, N
The Journal of emergency medicine. 2014;(2):184-90
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are potentially life-threatening complications of diabetes mellitus. Although DKA and HHS share similar features, they are distinct clinical entities requiring different treatment measures. OBJECTIVE This case illustrates that the clinical distinction between these two entities can be difficult at times, especially in children who can present with an overlapping picture. CASE REPORT We report an interesting case of a 12-year-old whose initial presentation of diabetes was a mixed picture of hyperosmolar DKA and HHS coma complicated by myocardial strain and acute renal insufficiency. The myocardial strain resolved completely with resolution of the metabolic abnormalities. CONCLUSIONS Emergency physicians should be cognizant of varied presentations of hyperglycemic emergencies in children to initiate appropriate management for better outcomes.