A Case of Type 1 Diabetes Mellitus With Endogenous Insulin Secretory Depletion Confirmed in Two Weeks.

Type 1 diabetes mellitus (T1DM) is manifested as a decrease in endogenous insulin secretion. With this report, we present a case of T1DM where a rapid decline in insulin secretion was observed in a short span of time. A 56-year-old female patient presented with cold-like symptoms with subsequent dry mouth and malaise to the hospital. Three weeks later, she was diagnosed with diabetic ketoacidosis based on the presence of hyperglycemia, metabolic acidosis, and positive ketone bodies. Her serum connecting peptide (CPR) levels substantially decreased (1.31 to 0.19 ng/mL after two weeks) and she was eventually diagnosed with T1DM. We hypothesized that a subtype T1DM with a longer beta cell loss rate than conventional fulminant type 1 diabetes was involved. This subtype showed characteristics of immune checkpoint inhibitor-associated fulminant type 1 diabetes and is suggested to exist among those diagnosed with conventional acute-onset type 1 diabetes. Finally, we recommend that diabetic ketoacidosis of unknown etiology should be investigated for the concurrent presence of T1DM.

Extensive-Disease Small-Cell Lung Cancer With Severe Immune-Related Adverse Events Due to Atezolizumab Maintaining a Complete Response for Two Years: A Case Report.

A 75-year-old male with diabetes mellitus was referred to our hospital with an abnormal shadow on chest radiography, based on which he was diagnosed with extensive-disease small-cell lung cancer (ED-SCLC; cT2bN2M1a). The first-line therapy comprised atezolizumab, carboplatin, and etoposide. After four cycles, the patient achieved complete response (CR), and maintenance therapy was initiated with atezolizumab. However, even though CR was maintained, maintenance therapy was discontinued after 16 cycles due to persistent grade 2 anorexia and fatigue. Simultaneously, the HbA1c decreased to 5.5%, and antidiabetic therapy was discontinued. Six months after the last dose of atezolizumab, the patient visited the emergency room because of anorexia, dry mouth, and fatigue. Laboratory findings were as follows: blood glucose was 668 mg/dL, glycated hemoglobin (HbA1c) was 8.8%, urine ketone was 2+, sodium (Na) was 127 mmol/L, potassium (K) was 6.5 mmol/L, creatinine (Cre) was 1.43 mg/dL, and arterial pH was 7.29. Based on these findings, his presentation was consistent with fulminant type 1 diabetes mellitus (T1DM) complicated by diabetic ketoacidosis (DKA). Regular continuous insulin and saline administration was initiated in the intensive care unit, and acidosis and electrolyte abnormalities were corrected. His C-peptide was <0.03 ng/mL. His insulin secretory capacity was considered to be depleted, and he required continuous subcutaneous insulin injections. Glutamic acid decarboxylase and insulin autoantibodies were absent. The complete response persisted without further therapy until two years since the event.

Rapid improvement of severe fatty liver in a case of fulminant type 1 diabetes following insulin treatment.

A 36-year-old woman presented to the emergency room with a consciousness disorder after developing abdominal pain with diarrhea for 2 days. She presented with marked hyperglycemia, ketoacidosis, and increased serum free fatty acid (FFA) levels; however, no elevation in the glycated hemoglobin (HbA1c) levels was observed. Based on the marked depletion of insulin secretion, the patient was diagnosed as diabetic ketoacidosis attributed to fulminant type 1 diabetes (FT1D). Computed tomography on admission revealed severe fatty liver (FL), which improved 17 h following insulin treatment. Insulin treatment also suppressed the serum FFA levels. Some cases of FT1D with FL and liver dysfunction have been reported previously; however, its pathogenesis and clinical course remain unclear. Compared to previous reports, this case reported the shortest time for FL improvement. In this case, rapid and severe insulin deficiency led to a markedly high FFA level and significant accumulation of triglycerides in the hepatocytes, resulting in severe FL. A rapid and large dose of insulin was administered when systemic insulin sensitivity was nearly maximal owing to insulin deficiency, increased insulin efficacy, early reduction of FFA, suppressed triglyceride accumulation in the hepatocytes, and increased triglyceride excretion from the liver. All these factors could have contributed to the rapid improvement in FL.

Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report.

BACKGROUND: Fulminant type 1 diabetes mellitus (FT1DM) that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM (PF), always without history of abnormal glucose metabolism. Here, we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus (GDM). CASE SUMMARY: The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected, and the patients and their infants were followed up. All patients were diagnosed with GDM during the second trimester and were treated. The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM. Two patients had an insulin allergy, and two had symptoms of upper respiratory tract infection before onset. One patient developed ketoacidosis, and three developed ketosis. Two patients had cesarean section deliveries, and two had vaginal deliveries. The growth and development of the infants were normal. C-peptide levels were lower than those at onset, suggesting progressive impairment of islet function. The frequencies of the DRB1 09:01, DQB1 03: 03, DQA1 03:02, DPA1 01:03, DPA1 02:02, DPB1 05:01, DRB4 01:03, G 01:01, and G 01:04 human leukocyte antigen (HLA)-G alleles were high in the present study. CONCLUSION: In comparison with pregnancy-associated FT1DM (PF), patients with GDM combined with FT1DM had an older age of onset, higher body mass index, slower onset, fewer prodromal symptoms, and less acidosis. The pathogenesis may be due to various factors affecting the already fragile ß-cells of GDM patients with genetically susceptible class II HLA genotypes. We speculate that GDM combined with FT1DM during pregnancy, referred to as "double diabetes," is a subtype of PF with its own unique characteristics that should be investigated further.

Fulminant type 1 diabetes with Shock rescue: a case report.

The shock in diabetes often requires rapid and adequate fluid administration, however, we report an anomalous case of fulminant type 1 diabetes mellitus (FT1DM) in which the patient's condition worsened following fluid administration. In May 2020, a 29-year-old male presented with blood glucose of 89.8 mmol/L and diabetic ketoacidosis after a week of gastroenteritis. The diagnosis was finalized after C-peptide and Hemoglobin A1c (HbA1c) measurement. The patient was admitted with shock and received a positive fluid balance of 2800 ml in 5 h, but his condition deteriorated and progressed to multi-organ failure. This study attempts to explain the possible mechanisms and focuses on high-risk factors associated with FT1DM. Therefore, meticulous monitoring and individualized fluid administration strategies are crucial for the management of FT1DM. This case provides beneficial insights for clinical treatment of this condition.

Clinical characteristics of patients with early-onset diabetes mellitus: a single-center retrospective study.

BACKGROUND: The prevalence of diabetes mellitus (DM) is dramatically increasing around the world, and patients are getting younger with changes in living standards and lifestyle. This study summarized and analyzed the clinical characteristics of different types of newly diagnosed diabetes mellitus patients with an onset age between 18 and 40 years to provide clinical evidence for the early diagnosis and treatment of diabetes, reduce short-term and long-term complications and offer scientific and personalized management strategies. METHODS: A total of 655 patients newly diagnosed with early-onset diabetes mellitus in the Department of Endocrinology, the First Medical Center of PLA General Hospital from January 2012 to December 2022 were retrospectively enrolled in this study, with an onset age of 18-40 years. Their clinical data were collected and investigated. All patients were divided into two groups according to whether they presented with diabetic microangiopathy. Similarly, patients with early-onset type-2 diabetes were grouped in accordance with whether they had ketosis at the time of diagnosis. Binary logistic regression analysis was performed to analyze risk factors, and receiver-operating characteristic (ROC) analysis was used to explore the predictive value of significant risk factors. RESULTS: The findings were as follows: (1) Of 655 enrolled patients, 477 (72.8%) were male and 178 (27.1%) were female, with a mean age of onset of was 29.73 years ± 0.24 SD. (2) The prevalence of early-onset diabetes was gradually increasing. Type-2 diabetes was the most common type of early-onset diabetes (491, 75.0%). The ages of onset of early-onset type-1 diabetes, type-2 diabetes and LADA were mainly 18-24 years, 25-40 years and 33-40 years, respectively. (3) Initial clinical manifestations of early-onset diabetes were classic diabetes symptoms (361, 55.1%), followed by elevated blood glucose detected through medical examination (207, 31.6%). (4) Binary logistic regression analysis suggested that high serum uric acid (UA), a high urinary albumin-to-creatinine ratio (UACR) and diabetic peripheral neuropathy (DPN) were risk factors for microangiopathy in early-onset diabetes patients (P < 0.05). The area under the curve (AUC) on ROC analysis of the combination of UA, UACR and DPN was 0.848, 95% CI was 0.818 ~ 0.875, sensitivity was 73.8% and specificity was 85.9%, which had higher predictive value than those of UA, UACR and DPN separately. (5) Weight loss, high glycosylated hemoglobin (HbA1c) and young onset age were risk factors for ketosis in patients with early-onset type-2 diabetes (P < 0.05). CONCLUSION: (1) Men were more likely to have early-onset diabetes than women. (2) Early-onset diabetes patients with high serum uric acid levels, high UACRs and peripheral neuropathy were prone to microangiopathy. Comprehensive evaluation of these risk factors could have higher predictive value in the prediction, diagnosis and treatment of microvascular lesions. (3) Patients with weight loss at onset, high HbA1c and young onset age were more likely to develop ketosis. Attention should be given to the metabolic disorders of these patients.

Isolated adrenocorticotropic hormone deficiency following immune checkpoint inhibitors treatment often occurs in polyglandular endocrinopathies.

BACKGROUND: With the increasing application of immune checkpoint inhibitors (ICI) in cancer therapy, the occurrence of isolated adrenocorticotropic hormone deficiency (IAD), as an adverse effect, is also on the rise. Nevertheless, there are only a few studies regarding IAD induced by ICI. This study aimed at investigating the characteristics of IAD induced by ICI and its relationship with other endocrine adverse events. METHODS: A retrospective study was conducted in the Endocrinology Department from January 2019 to August 2022 to investigate characteristics of patients with IAD. Clinical features, laboratory findings and treatment information were collected. All patients underwent a follow-up of 3-6-month. RESULTS: 28 patients with IAD were enrolled. All patients received treatment with anti-PD-1/ PD-L1. The median occurrence time of IAD was 24 (18-39) weeks after initiation of ICI treatment. Over half of the patients (53.5%) had an additional endocrinopathy, including primary hypothyroidism and fulminant type 1 diabetes mellitus (FT1DM), while other types of endocrinopathies were not identified. The interval between the occurrences of two gland damages was between 4 and 21 weeks or simultaneous. Primary hypothyroidism (46.4%) was more prevalent than FT1DM (7.1%). Fatigue and nausea were common symptoms, with a frequent occurrence of hyponatremia. All patients continued on oral glucocorticoids during follow-up. CONCLUSIONS: IAD induced by ICI could manifest independently, or more frequently in combination with hypothyroidism or FT1DM. This damage could happen at any point of ICI treatment. Given that IAD can be life-threatening, it is critical to evaluate pituitary function dynamically in patients undergoing immunotherapy.

[Clinical Analysis of 17 Adult Patients With Fulminant Type 1 Diabetes Mellitus].

Objective: To explore the clinical characteristics of adult patients with fulminant type 1 diabetes mellitus (FT1DM), a specific subtype of type 1 diabetes mellitus (T1DM). Methods: We collected the clinical data of patients who were admitted to West China Hospital, Sichuan University in 2010-2019 for FT1DM and type 1 diabetes mellitus (T1DM) presenting with diabetic ketoacidosis (DKA) at the onset. In addition, all the FT1DM patients were followed up. Results: A total of 70 patients presenting with DKA at the onset of T1DM were admitted to and received treatment at West China Hospital in 2010-2019. Among them, 17 (24.3%) had FT1DM and 53 did not. The mean ages of the FT1DM patients and the non-FT1DM patients were (33.2±12.8) years and (27.5±11.2) years, and the mean body mass indices were (22.6±2.9) kg/m 2 and (19.2±2.9) kg/m 2, respectively. A total of 14 FT1DM cases had symptoms of upper respiratory tract infection or acute gastroenteritis before the onset of the disease and 4 cases were related to pregnancy. The median time from the onset of the disease to the first diagnosis of DKA of the FT1DM group (median [P 25-P 75]: 2 [1-4] days, P<0.001) was significantly shorter than that of the non-FT1DM group (median [P 25-P 75]: 30 [17-78] days). The mean maximum blood glucose levels at the time of the first visit to the doctor of the FT1DM patients ([39.9±11.4] mmol/L, P<0.001) were significantly higher than that of the non-FT1DM patients ([28.9±9.2] mmol/L), but the HbA1c (6.6%±0.6%, P<0.001) and glycosylated serum albumin (GA) (21.4%±3.0%, P=0.001) levels of the FT1DM patients were significantly lower than those of the non-FT1DM group (HbA1c: 12.8%±2.7%; GA: 44.8%±15.0%). The median serum amylase in the FT1DM group was significantly higher than that in the non-FT1DM group (101 [54-336] IU/L vs. 54 [42-166] IU/L, P=0.045) and the median serum lipase in the FT1DM group showed a trend of being higher than that in the T1DM group (81 [57-154] IU/L vs. 46 [28-195] IU/L, P=0.051). 8.7% of the non-FT1DM patients tested positive for anti-glutamic acid decarboxylase antibody (GAD-Ab), while the FT1DM patients all tested negative. At the time of discharge, the mean daily insulin dose of the FT1DM patients was (0.67±0.22) IU/kg, which was not significantly different from that of the non-FT1DM group ([0.74±0.29] IU/kg, P=0.349). After about 6.5 years of follow-up, the mean daily insulin dose of the FT1DM patients was (0.73±0.19) IU/kg, which was similar to the insulin dosage on discharge ( P=0.409). Conclusion: Compared with the non-FT1DM patients presenting with DKA at the onset, FT1DM patients have fewer typical diabetic symptoms, lower fasting C-peptide levels, higher serum amylase levels, and increased incidence of vomiting or other symptoms of gastrointestinal infections, and are more likely to be misdiagnosed. Therefore, it is very important for clinicians to correctly identify FT1DM as early as possible and administer early and long-term insulin replacement therapy.

Case report: A case of fulminant type 1 diabetes mellitus after COVID-19 vaccination during treatment of advanced gastric cancer: pitfall in managing immune-related adverse events.

The occurrence of fulminant type 1 diabetes mellitus as an adverse event during cancer immunotherapy has been previously reported. However, little is known about the causal relationship between the coronavirus disease 2019 (COVID-19) vaccination and fulminant type 1 diabetes mellitus. A 60-year-old man with advanced gastric cancer, receiving S-1 + oxaliplatin and nivolumab therapy, followed by nab-paclitaxel + ramucirumab as a second-line treatment, with steroid supplementation for complications of hypopituitarism-induced hypoadrenocorticism, was administered a COVID-19 vaccine after three cycles of nab-paclitaxel + ramucirumab. Two days later, he developed severe malaise and anorexia, which required emergency admission to our hospital for suspected adrenal insufficiency. Despite increasing steroids, his general condition changed suddenly after 12 hours leading to his death. Histopathological analysis of autopsy samples revealed loss of the islets of Langerhans, indicating fulminant type 1 diabetes mellitus. We failed to recognize the onset of fulminant type 1 diabetes mellitus because its symptoms were similar to those of adrenal insufficiency. The number of reports on the onset of fulminant type 1 diabetes mellitus after COVID-19 vaccination has been increasing, and in this case, the onset occurred on the second day after COVID-19 vaccination, suggesting an association between vaccination and fulminant type 1 diabetes mellitus. Clinicians should be aware of the risk of fulminant type 1 diabetes mellitus, although rare, after COVID-19 vaccination.

A rare case of a mother with gestational diabetes complicated with fulminant type 1 diabetes mellitus post-delivery.

Fulminant type 1 diabetes mellitus (FT1DM) is recognised as a novel subtype of type 1 diabetes mellitus characterised by the abrupt onset of insulin-deficient hyperglycaemia and ketoacidosis. Fulminant type 1 diabetes mellitus is known to be associated with pregnancy and had been associated with high fetal mortality. We report a case of a gestational diabetes mellitus (GDM) mother complicated with FT1DM immediately post-delivery. A 29-year-old Malay lady who was diagnosed with GDM at 19 weeks of pregnancy, underwent emergency lower segment caesarean section (EMLSCS) due to fetal distress at 36 weeks of gestation; 18 h post-EMLSCS, she developed abrupt onset Diabetic ketoacidosis (DKA) (blood glucose 33.5 mmol/L, pH 6.99, bicarbonate 3.6 mmol/L, ketone 4.4 mmol/L and HbA1c 6.1%). She received standard DKA treatment and discharged well. Her plasma C-peptide level 3 weeks later showed that she has no insulin reserve (C-peptide <33 pmol/L, fasting blood glucose (FBS) 28 mmol/L). Her pancreatic autoantibodies were negative. This case highlights that FT1DM not only can occur in pregnancy with normal glucose tolerance but can also complicate mother with GDM.

Fulminant Type 1 Diabetes Mellitus Associated With Drug Hypersensitivity and Epstein-Barr Virus Infection: A Case Report.

Background: Fulminant type 1 diabetes mellitus (FT1DM) is a new subtype of type 1 diabetes, first proposed by Japanese scholars in 2000. Herein, the functions of the islets are rapidly destroyed. Its pathogenesis is related to viral infection. Most people have been infected with Epstein-Barr virus (EBV), and many people have also suffered from drug hypersensitivity, however, few cases of FT1DM which were caused by both of the two conditions have been reported. Thus, below, we describe one such valuable case. Case Summary: The plasma glucose levels of a 73-year-old man diagnosed with drug-induced dermatitis showed a sudden increase (42 mmol/L) during methylprednisolone therapy. The urine ketone test was positive. The glycated hemoglobin level was 7%, endogenous insulin secretion decreased significantly, and the islet-related autoantibodies were negative. The patient was diagnosed with FT1DM. The lymphocyte EBV-DNA showed high copies numbers. The general condition of the patient improved after symptomatic treatment with insulin. However, the systemic allergic reaction aggravated after the use of iodinated contrast agents, prednisone, and thymic pentapeptide. The re-test for EBV-DNA showed significantly high relative levels, thus indicating the presence of EBV infection. We think that drug hypersensitivity and EBV infection together led to FT1DM in this case. After an indication for multiple daily insulin therapy, the patient's blood glucose was quickly controlled and he was discharged on the 38th-day post-admission. Conclusion: FT1DM is a rare case, however, drug hypersensitivity and EBV infection are not rare in the population. This is a rare case of FT1DM caused by drug hypersensitivity reaction and EBV infection. Through this case report, we emphasize the importance of the relationship between drug hypersensitivity, EBV infection and FT1DM and vigilance for the occurrence of FT1DM among hypersensitive individuals in clinical practice.

Development of a hyperosmolar-hyperglycemic state and possible fulminant type 1 diabetes mellitus during the treatment of a case of adenocarcinoma of the lung and interstitial pneumonia.

An 85-year-old man was being treated with anti-cancer drugs for adenocarcinoma of the lung and was on a tapering dose of prednisolone for interstitial pneumonia. He attended our hospital complaining of fatigue, thirst, and polyuria in September 2020. His postprandial plasma glucose concentration was 976 mg/dL, his glycated hemoglobin was 8.0%, his plasma osmolality was 342 mOsm/kg H2O, his urine ketone body content was 1 +, and his blood pH was 7.356. Therefore, we diagnosed a hyperosmolar-hyperglycemic state and he was admitted to the hospital for treatment. He had had no previous upper respiratory symptoms, and his postprandial plasma glucose and glycated hemoglobin were normal 13 days before he was first assessed (90 mg/dL and 5.9%, respectively). On admission, his serum pancreatic exocrine enzyme activities were high and he was negative for islet-specific autoantibodies. His serum C-peptide concentration was 0.60 ng/mL, suggesting that his endogenous insulin secretion was partially intact at that time. Although he did not meet the diagnostic criteria, we suspected him of having fulminant type 1 diabetes mellitus, because of the abrupt onset of hyperosmolar-hyperglycemic state. His general condition was improved by fluid and insulin administration. His human leukocyte antigen genotype was DRB1*04:05 DQB1*04:01:01, which is a disease susceptibility haplotype for fulminant type 1 diabetes mellitus. In addition, his prednisolone treatment may have caused an autoimmune abnormality, further predisposing toward the development of fulminant type 1 diabetes mellitus.

Changes in glucagon secretion induced by food intake in fulminant type 1 diabetes mellitus: a case report.

Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus and is characterized by a remarkably abrupt onset and almost complete destruction of ß-cells within a few days. Here, we report a case of diabetic ketoacidosis in a 63-year-old man with no history of hyperglycemia. The patient was diagnosed with FT1DM and had almost no insulin secretion. We examined his insulin and glucagon secretions induced by a liquid meal test at the onset of FT1DM and 1 year later. The results suggested severely attenuated insulin secretion and an undetectable level of serum insulin 1 year after onset. In contrast, glucagon secretion, which was highly impaired at onset, increased in response to food intake. Although previous reports have suggested that both ß- and α-cells of pancreatic islets are damaged in patients with FT1DM, the number of α-cells may increase over time after the onset of FT1DM.

Prevalence and clinical characteristics of fulminant type 1 diabetes mellitus in Korean adults: A multi-institutional joint research.

AIMS/INTRODUCTION: We aimed to determine the hospital-based prevalence and clinical features of fulminant type 1 diabetes mellitus in Korea. MATERIALS AND METHODS: We identified all patients with diabetes who regularly visited the Endocrinology outpatient clinics at eight centers for a period >1 year between January 2012 and June 2017. We investigated their medical records retrospectively. RESULTS: During this period, 76,309 patients with diabetes had been regularly followed up. Among them, 913 (1.2%) patients had type 1 diabetes mellitus . There were 462 patients with type 1 diabetes mellitus whose data at the time of the first diagnosis could be identified (359 and 103 with non-ketosis and ketosis onset, respectively). Of these, 15 (3.2% of type 1 diabetes mellitus, 14.6% of ketosis onset diabetes) patients had fulminant type 1 diabetes mellitus. The median ages at diagnosis were 40 and 27 years in the fulminant type 1 diabetes mellitus and non-fulminant type 1 diabetes mellitus groups, respectively. The patients with fulminant type 1 diabetes mellitus had higher body mass index, lower glycated hemoglobin and fasting/peak C-peptide, and lower frequent glutamic acid decarboxylase antibody-positive rate (P =0.0010) at diagnosis. Furthermore, they had lower glycated hemoglobin at the last follow-up examination than those with non-fulminant type 1 diabetes mellitus. CONCLUSIONS: In this study, the prevalence of type 1 diabetes mellitus was 1.2% among all patients with diabetes, and that of fulminant type 1 diabetes mellitus was 3.2% among those newly diagnosed with type 1 diabetes mellitus. The glycated hemoglobin levels were lower in patients with fulminant type 1 diabetes mellitus than in those with non-fulminant type 1 diabetes mellitus at diagnosis and at the last follow-up examination.

Classic Type 1 Diabetes Mellitus and Fulminant Type 1 Diabetes Mellitus: Similarity and Discrepancy of Immunological Characteristics and Cytokine Profile.

PURPOSE: We aimed to explore the immunological characteristics and cytokine profile of the initial stage of type 1 diabetes. PATIENTS AND METHODS: In total, 123 age- and sex-matched subjects with newly diagnosed classic type 1 diabetes mellitus (T1ADM), fulminant type 1 diabetes mellitus (FT1DM), and normal glucose tolerance (NGT) were enrolled. Serum cytokine levels were measured using Milliplex MAP multifactor detection. RESULTS: There was a significant increase in the levels of transforming growth factor ß (TGFß1) and TGFß2 and decrease in programmed death-1 (PD-1), PD ligand 1 (PD-L1), pro-inflammatory cytokines, and anti-inflammatory cytokines in type 1 diabetes patients compared with the NGT subjects (all P < 0.05). There was no significant difference in C-reactive protein (CRP) and blood routine indicators between the two groups. Type 1 diabetes was further divided into T1ADM and FT1DM subgroups. FT1DM patients had much higher CRP levels than T1ADM patients (4.90 [0.95-26.05] mg/L vs 0.39 [0.20-0.74] mg/L, P < 0.01). Blood routine results showed that the number of leukocytes was significantly increased in FT1DM compared with that in T1ADM (9.2 [5.1-18.8] × 109 cells/L vs 5.4 [4.5-6.7] × 109 cells/L, P < 0.01). In FT1DM patients, neutrophil% was increased, and lymphocyte% was declined significantly, compared with that in T1ADM patients (neutrophil%: 80.2 [59.2-85.2]% vs 59.5 [54.8-64.0]%; lymphocyte%: 18.3 [10.1-32.3]% vs 32.6 [26.8-35.9]%; both P < 0.01). However, there was no difference between FT1DM and T1ADM in cytokine profile except for the decrease in CTLA-4 in T1ADM (P < 0.05). CONCLUSION: Compared with T1ADM, CRP and leukocytes' levels were increased significantly in FT1DM, with an increase in neutrophil% and decline in lymphocyte%, suggesting that FT1DM may have more abrupt onset and occur as a more serious subtype of type 1 diabetes mellitus.

[A case of fulminant type 1 diabetes mellitus in an elderly patient who developed cardiopulmonary arrest from diabetic ketoacidosis and whose imaging course was monitored].

A 71-year-old man with a history of hypertension and nephrosclerosis visited a primary care doctor for a regular visit. After a few days of vomiting and diarrhea, gastroenteritis was suspected and he was prescribed medication for these symptoms by his previous doctor. The next morning, he visited our hospital complaining of malaise and abdominal distention.The patient's blood glucose level was 1,385 mg/dL, his arterial blood pH was 6.885 (followed by an elevated serum ketone level), and hyperkinesis from diabetic ketoacidosis (DKA) was observed. The patient had experienced cardiopulmonary arrest, likely due to ventricular fibrillation. After cardiopulmonary resuscitation, the patient was admitted to hospital and treated for DKA. The urinary and serum C-peptide levels were below the limit of sensitivity, and anti-glutamic acid decarboxylase antibody and anti-insulinoma-associated antigen-2 antibody were not detected in the serum. These findings were consistent with a diagnosis of fulminant type 1 diabetes mellitus. We herein report a rare case of resuscitation in an elderly patient with fulminant-onset type 1 diabetes mellitus. We carefully observed the imaging history of the patient with great interest.

Fulminant Type 1 Diabetes Mellitus Developed about Half a Year after Discontinuation of Immune Checkpoint Inhibitor Combination Therapy with Nivolumab and Ipilimumab: A Case Report.

The cytotoxic T-lymphocyte antigen-4 and programmed cell death 1 pathways are novel therapeutic targets in immune checkpoint inhibitor (ICI) therapy for cancer. However, they may cause endocrine-related adverse events, including hypophysitis, autoimmune thyroiditis and type 1 diabetes mellitus (DM). Moreover, delayed immune-related adverse events (irAEs) after discontinuation of ICI therapy have been reported. Here we report a 60-year-old female patient with advanced renal cell carcinoma with brain metastasis who was treated with nivolumab, ipilimumab and prednisolone. At the 3rd course of combination therapy, the administration was discontinued due to the onset of colitis and the dosage of prednisolone was increased. About half a year after discontinuation, she was admitted to the hospital with general malaise, hyperglycemia (330 mg/dL) and diabetic ketoacidosis. Glycated hemoglobin level was 6.5%. Islet-related autoantibodies were negative. The glucagon tolerance test showed complete depletion of insulin. Therefore, we diagnosed fulminant type 1 DM and treated with multiple daily injections of insulin. The onset of type 1 DM was rapid in many cases treated with combination therapy of ICIs. The present case is a rare case in which fulminant type 1 DM developed about half a year after discontinuation of nivolumab and ipilimumab. The literature shows two cases of type 1 DM occurring 4 months after discontinuation of ICI therapy by nivolumab or atezolizumab. The present case indicates that regular monitoring is mandatory for fulminant type 1 DM and other delayed irAEs after discontinuation of ICI therapy even under the low-dose prednisolone treatment.

Case Report: Infantile-Onset Fulminant Type 1 Diabetes Mellitus Caused by Novel Compound Heterozygous LRBA Variants.

Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is a subtype of common variable immune deficiency (CVID). Numerous case reports and cohort studies have described a broad spectrum of clinical manifestations and variable disease phenotypes, including immune dysregulation, enteropathy, and recurrent infections. Although LRBA deficiency is an autosomal recessive primary immunodeficiency resulting in a phenotype similar to CVID, it is a monogenic disease and separate from CVID. Recently, in a report of monogenic primary immunodeficiency disorder associated with CVID and autoimmunity, the most common mutated gene was LRBA. We report the case of a girl who presented with fulminant type 1 diabetes at age 7 months. She later experienced recurrent bacterial infections with neutropenia and idiopathic thrombocytopenic purpura. Clinical genome sequencing revealed compound heterozygosity of the LRBA gene, which bore two novel mutations. A genetic basis should be considered in the differential diagnosis for very young patients with fulminant autoimmunity, and the diagnostic work-up should include evaluation of markers of immunodeficiency.

Transition of blood glucose level in a patient with pregnancy-associated fulminant type 1 diabetes mellitus.

We report on the transition in blood glucose levels before and after the onset of fulminant type 1 diabetes mellitus in a perinatal woman. In week 38 of pregnancy, before which the patient had normal glucose tolerance, idiopathic acute pancreatitis was diagnosed. Five days thereafter, she became hypoglycemic, so we closely monitored her blood glucose levels. A total of 13 days later, she was hyperglycemic with a blood glucose level >16.0 mmol/L and glycated hemoglobin of 6.4%. Her fasting serum C-peptide reactivity level was 3.6 ng/mL on the 5th day, and 0.2 ng/mL on the 18th day. Multiple insulin injection therapy was administered since the 18th day; after that, ketoacidosis did not occur. The patient was diagnosed with fulminant type 1 diabetes mellitus based on hyperglycemia without high glycated hemoglobin levels and sudden onset insulin-dependent diabetes. Monitoring glucose levels in the case of idiopathic acute pancreatitis during pregnancy and prompt initiation of insulin therapy are important.