OBJECTIVES: Programmed death 1 (PD-1) associated fulminant type 1 diabetes (PFD) is a rare acute and critical in internal medicine, and its clinical characteristics are still unclear. This study aims to analyze the clinical characteristics of PFD patients to improve clinical diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 10 patients with PFD admitted to the Second Xiangya Hospital of Central South University, combined with the data of 66 patients reported in the relevant literature, analyzed and summarized their clinical and immunological characteristics, and compared the patients with PFD with different islet autoantibody status. RESULTS: Combined with our hospital and literature data, a total of 76 patients with PFD were reported, with the age of (60.9±12.1) years old, 60.0% male and body mass index of (22.1±5.2) kg/m2. In 76 patients, the most common tumors were lung cancer (43.4%) and melanoma (22.4%). Among PD-1 inhibitors, the most common drugs are nivolumab (37.5%) and pembrolizumab (38.9%). 82.2% of PFD patients developed diabetes ketoacidosis. The median onset time from PD-1 related inhibitor treatment to hyperglycemia was 95 (36.0, 164.5) d, and the median treatment cycle before the onset of diabetes was 6 (2.3, 8.0) cycles. 26% (19/73) of PFD patients had positive islet autoantibodies, and the proportion of ketoacidosis in the positive group was significantly higher than that in the negative group (100.0% vs 75.0%, P<0.05). The onset time and infusion times of diabetes after PD-1 inhibitor treatment in the autoantibody positive group were significantly lower than those in the autoantibody negative group (28.5 d vs 120.0 d; 2 cycles vs 7 cycles, both P<0.001). CONCLUSIONS After initiation of tumor immunotherapy, it is necessary to be alert to the occurrence of adverse reactions of PFD, and the onset of PFD with islet autoantibody positive is faster and more serious than that of patients with autoantibodies negative. Detection of islet autoantibodies and blood glucose before and after treatment with PD-1 inhibitors is of great value for early warning and prediction of PFD.
Humans ; Male ; Middle Aged ; Aged ; Female ; Diabetes Mellitus, Type 1 ; Programmed Cell Death 1 Receptor ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Ketosis ; Autoantibodies

Humans ; Diabetes Mellitus ; Ketosis ; Magnetic Resonance Imaging

In recent years, reports of diabetes mellitus (DM) cases that do not fit the traditional classification system have increased in prevalence. While insulin deficiency appears as type 1 DM (T1DM), the new type also has the clinical features of type 2 DM (T2DM); as such, this new type of DM is called ketosis-prone diabetes (KPD) and is correlated with findings of severe hyperglycemia and ketoacidosis. To provide a clear, clinical classification of DM, new classification systems are being studied. Among these, the Aβ system demonstrates the highest sensitivity and specificity in predicting clinical features and prognosis. We report 2 cases of KPD in Korean pediatric patients. The first patient was referred while in a state of diabetic ketoacidosis (DKA) and was considered to have T1DM. However, their blood glucose was well-controlled even with small doses of insulin, and the treatment was able to be changed to metformin therapy. The second patient seemed to be a typical case of T2DM because of his obesity and strong family history. However, blood glucose was not well-controlled with a regular diet, and ketosis occurred. After performing a glucagon stimulation test, both patients showed different clinical features that were finally diagnosed as type A-β+ KPD. The rapid and accurate diagnosis of KPD can reduce the duration of inappropriate insulin use and improve patients' quality of life. Further, the treatment of KPD children should be individualized according to each patient's lifestyle to preventing recurrent DKA.
Adolescent ; Blood Glucose ; Child ; Classification ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetic Ketoacidosis ; Diagnosis ; Diet ; Glucagon ; Humans ; Hyperglycemia ; Insulin ; Ketosis ; Life Style ; Metformin ; Obesity ; Prevalence ; Prognosis ; Quality of Life ; Sensitivity and Specificity

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare inborn error of ketone body utilization, characterized by episodic or permanent ketosis. SCOT deficiency is caused by mutations in the OXCT1 gene, which is mapped to 5p13 and consists of 17 exons. A 12-month-old girl presented with severe ketoacidosis and was treated with continuous renal replacement therapy. She had two previously unrecognized mild-form episodes of ketoacidosis followed by febrile illness. While high levels of ketone bodies were found in her blood and urine, other laboratory investigations, including serum glucose, were unremarkable. We identified novel compound heterozygous mutations in OXCT1:c.1118T>G (p.Ile373Ser) and a large deletion ranging from exon 8 to 16 through targeted exome sequencing and microarray analysis. This is the first Korean case of SCOT deficiency caused by novel mutations in OXCT1, resulting in life-threatening ketoacidosis. In patients with unexplained episodic ketosis, or high anion gap metabolic acidosis in infancy, an inherited disorder in ketone body metabolism should be suspected.
Acid-Base Equilibrium ; Acidosis ; Blood Glucose ; Exome ; Exons ; Female ; Humans ; Infant ; Ketone Bodies ; Ketosis ; Metabolism ; Microarray Analysis ; Renal Replacement Therapy ; Transferases

Quercetin and resveratrol are known to have beneficial effects on the diabetes and diabetic complication, however, the effects of combined treatment of these compounds on diabetes are not fully revealed. Therefore, the present study was designed to investigate the combined antidiabetic action of quercetin (QE) and resveratrol (RS) in streptozotocin (STZ)-induced diabetic rats. To test the effects of co-treated with these compounds on diabetes, serum glucose, insulin, lipid profiles, oxidative stress biomarkers, and ions were determined. Additionally, the activities of hepatic glucose metabolic enzymes and histological analyses of pancreatic tissues were evaluated. 50 male Sprague-Dawley rats were divided into five groups; normal control, 50 mg/kg STZ-induced diabetic, and three (30 mg/kg QE, 10 mg/kg RS, and combined) compound-treated diabetic groups. The elevated serum blood glucose levels, insulin levels, and dyslipidemia in diabetic rats were significantly improved by QE, RS, and combined treatments. Oxidative stress and tissue injury biomarkers were dramatically inhibited by these compounds. They also shown to improve the hematological parameters which were shown to the hyperlactatemia and ketoacidosis as main causes of diabetic complications. The compounds treatment maintained the activities of hepatic glucose metabolic enzymes and structure of pancreatic β-cells from the diabetes, and it is noteworthy that cotreatment with QE and RS showed the most preventive effect on the diabetic rats. Therefore, our study suggests that cotreatment with QE and RS has beneficial effects against diabetes. We further suggest that cotreatment with QE and RS has the potential for use as an alternative therapeutic strategy for diabetes.
Animals ; Biomarkers ; Blood Glucose ; Diabetes Complications ; Dyslipidemias ; Glucose ; Humans ; Hyperlactatemia ; Insulin ; Ions ; Ketosis ; Male ; Oxidative Stress ; Quercetin* ; Rats* ; Rats, Sprague-Dawley ; Streptozocin

Fulminant type 1 diabetes is a distinct subtype of type 1 diabetes mellitus that is characterized by sudden, complete destruction of pancreatic beta cells at the disease onset. Since the disease was first described in 2000 in Japan, a number of case reports have also been published in Korea. However, this disease entity is still not well defined. A 48-year old man with no medical history was admitted with diabetic ketoacidosis. Fulminant type 1 diabetes was diagnosed and he was discharged with multiple insulin injections. His serum glucose level was well controlled in the outpatient clinic. A month later, diabetic ketoacidosis occurred again following a diagnostic colonoscopy. This case suggests that fulminant type 1 diabetes is an aggressive disease in which small stimuli can provoke ketoacidosis. Therefore, for tests that require fasting, close observation by medical staff and patient education about the disease is essential.
Ambulatory Care Facilities ; Blood Glucose ; Colonoscopy* ; Diabetes Mellitus, Type 1 ; Diabetic Ketoacidosis* ; Fasting ; Humans ; Insulin ; Insulin-Secreting Cells ; Japan ; Ketosis ; Korea ; Medical Staff ; Patient Education as Topic

Diabetic ketoacidosis (DKA) is serious complication of diabetes mellitus that requires prompt recognition, diagnosis and treatment. It is characterized by a triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration. The overall DKA mortality rate recorded among children and adults is < 1%. For patients with DKA, appropriate administration of intravenous fluids and insulin with attention to associated fluid and electrolyte disorders can effectively and rapidly resolve metabolic dysregulation. Following acute management and restoration of physiological glucose levels, DKA requires identification of the precipitating cause to prevent recurrence of potentially life-threatening diabetic complications.
Acidosis ; Adult ; Child ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Ketoacidosis* ; Diagnosis ; Glucose ; Humans ; Hyperglycemia ; Insulin ; Ketosis ; Mortality ; Recurrence

Permanent neonatal diabetes mellitus is most commonly caused by mutations in the ATP-sensitive potassium channel (KATP) subunits. Prompt initiation of sulfonylurea treatment can improve glycemic control in children with KCNJ11 mutation. In this report, we present a case of permanent neonatal diabetes caused by a mutation in the KCNJ11 gene that was successfully treated via early switching of insulin to sulfonylurea treatment. A 53-day-old female infant presented with diabetic ketoacidosis. Insulin was administered for the ketoacidosis and blood glucose regulation. At 3 months of age, using genomic DNA extracted from peripheral lymphocytes, direct sequencing of KCNJ11 identified a heterozygous mutation of c.158G>A (p.G53D) and confirmed the diagnosis of permanent neonatal diabetes mellitus. Subsequently, treatment with sulfonylurea was initiated, and the insulin dose was gradually tapered. At 4 months of age, insulin therapy was discontinued, and sulfonylurea (glimepiride, 0.75 mg/kg) was administered alone. At 6 months after initiation of administration of sulfonylurea monotherapy, blood glucose control was stable, and no hypoglycemic events or developmental delays were reported. C-peptide levels increased during treatment with sulfonylurea. Early switching to sulfonylurea in infants with permanent diabetes mellitus owing to a KCNJ11 mutation could successfully help regulate glycemic control, which suggests the need for early genetic testing in patients presenting with diabetes before 6 months of age.
Blood Glucose ; C-Peptide ; Child ; Diabetes Mellitus ; Diabetic Ketoacidosis ; Diagnosis ; DNA ; Female ; Genetic Testing ; Humans ; Infant* ; Infant, Newborn ; Insulin* ; Ketosis ; Lymphocytes ; Potassium Channels

Fulminant type 1 diabetes mellitus (FT1DM) is a clinical entity in which the process of beta-cell destruction and subsequent progression of hyperglycemia and ketoacidosis are extremely rapid. A 34-year-old woman without any known risk factor for diabetes mellitus experienced a sudden stillbirth at 30 weeks of gestation. She had normal oral glucose tolerance test during pregnancy. Her blood glucose level was 974 mg/dL. Her urine test for ketone bodies was positive. Her hemoglobin A1c level (6.8%) was near normal range at the first emergency room visit. These findings suggested a very recent onset of diabetes mellitus. Her serum C-peptide level was very low. Islet-related autoantibodies were undetectable. Her clinical course, biochemical, and immunological profiles were consistent with FT1DM. After fluid and insulin based management, beta-cell was rescued with insulin therapy during the evolution of FT1D. At 10 days after admission, maintenance dose of insulin was just 8 unit of insulin once daily. This is the first case of FT1DM with robust recovery in insulin secretion in a pregnant woman who had an initial manifestation of 3rd-trimester intrauterine fetal death in Korea.
Adult ; Autoantibodies ; Blood Glucose ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Emergency Service, Hospital ; Female ; Fetal Death* ; Glucose Tolerance Test ; Humans ; Hyperglycemia ; Insulin* ; Ketone Bodies ; Ketosis ; Korea ; Pregnancy ; Pregnant Women* ; Reference Values ; Risk Factors ; Stillbirth

Recurrent acute pancreatic attacks is a rare clinical condition (2-5% of all acute pancreatis) in children and is mainly idiopathic in most cases. Sometimes it may be associated with congenital anomalies, metabolic diseases or hereditary conditions. Isovaleric acidemia (IVA) is a rare autosomal recessive amino acid metabolism disorder associated with isovaleryl coenzyme A dehydrogenase deficiency presenting the clinical findings such metabolic acidosis with increased anion gap, hyperammonemia, ketonemia, hypoglycemia, “the odor of sweaty feet,” abdominal pain, vomiting, feeding intolerance, shock and coma. Recurrent acute pancreatitis associated with IVA have been rarely reported. Herein; we report a child who admitted with recurrent acute pancreatic attacks and had the final diagnosis of IVA. Mutation analysis revealed a novel homozygous mutation of (p.E117K [c.349G>A]) in the IVA gene. Organic acidemias must kept in mind in the differential diagnosis of recurrent acute pancreatic attacks in children.
Abdominal Pain ; Acid-Base Equilibrium ; Acidosis ; Child* ; Coma ; Diagnosis ; Diagnosis, Differential ; Humans ; Hyperammonemia ; Hypoglycemia ; Isovaleryl-CoA Dehydrogenase ; Ketosis ; Metabolic Diseases ; Metabolism ; Odors ; Pancreatitis* ; Shock ; Vomiting