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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.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Diabetes Mellitus Tipo 1 , Receptor de Morte Celular Programada 1 , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Cetose , AutoanticorposRESUMO
Type 1 diabetes mellitus (T1DM) is an organ-specific disease characterized by autoimmune damage to pancreatic β cells. Insulin therapy is the most basic and important treatment for T1DM, but insulin therapy cannot fundamentally terminate or improve the main cause of T1DM, namely the disorder of the immune regulation mechanism. With the advancement of science and technology, the continuous development of new insulin and hypoglycemic drugs has provided better means for glycemic control. Pancreas transplantation, islet transplantation, immunotherapy, and cell therapy have provided hope for the prevention or reversal of T1DM. It is of great significance to understand the current situation and future of new technologies for T1DM treatment for the research and management of T1DM patients.
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Diabetes is a group of clinical syndromes with multiple causes and pathologies resulting from multiple factors. Different types of diabetes have different intrinsic types and complex clinical phenotypes according to genetics, immunology, metabolism, and clinical characteristics. Latent autoimmune diabetes in adults and ketosis-prone diabetes are the manifestation of clinical heterogeneity among different types of diabetes. High clinical heterogeneity gradually obscures the classic differences between diabetes types and leads to the emergence of new forms of diabetes. The high heterogeneity of diabetes poses challenges to the accurate classification of diabetes mellitus. It has significance in the prediction, prevention, diagnosis, and treatment of the disease for us to have a deep understanding of the clinical consequences of heterogeneity within and between different diabetes types.
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Objective@#To evaluate the association between NLRP2(NLR Family Pyrin Domain Containing 2) gene polymorphisms and classical type 1 diabetes mellitus(T1DM) in Chinese Han population.@*Methods@#A case-control study was conducted in 510 classical T1DM patients from the Department of Metabolism and Endocrinology in the Second Xiangya Hospital affiliated to Central South University and 531 healthy controls in this region. The polymorphisms of rs1043673 in NLRP2 gene were analyzed by MassARRAY. Mann-Whitney U test and χ2 test were used to compare the differences between patients and controls. Logistic regression analysis and χ2 test were performed to compare the distributions of the alleles and genotypes between T1DM patients and controls. Kruskal-Wallis H test was used to compare the clinical characteristics of different genotypes in T1D patients.@*Results@#The differences of the allele and genotype distributions in rs1043673 of NLRP2 gene were not significant between patients and controls. The polymorphisms of rs1043673 were associated with fasting C-peptide(P=0.029), postprandial 2-h C-peptide(P=0.017), and titer of GADA(P=0.043) in T1DM patients.@*Conclusion@#The polymorphisms of NLRP2 gene were associated with the characteristics of T1DM patients.
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Objective:To evaluate the association between NLRP2(NLR Family Pyrin Domain Containing 2) gene polymorphisms and classical type 1 diabetes mellitus(T1DM) in Chinese Han population.Methods:A case-control study was conducted in 510 classical T1DM patients from the Department of Metabolism and Endocrinology in the Second Xiangya Hospital affiliated to Central South University and 531 healthy controls in this region. The polymorphisms of rs1043673 in NLRP2 gene were analyzed by MassARRAY. Mann- Whitney U test and χ2 test were used to compare the differences between patients and controls. Logistic regression analysis and χ2 test were performed to compare the distributions of the alleles and genotypes between T1DM patients and controls. Kruskal- Wallis H test was used to compare the clinical characteristics of different genotypes in T1D patients. Results:The differences of the allele and genotype distributions in rs1043673 of NLRP2 gene were not significant between patients and controls. The polymorphisms of rs1043673 were associated with fasting C-peptide( P=0.029), postprandial 2-h C-peptide( P=0.017), and titer of GADA( P=0.043) in T1DM patients. Conclusion:The polymorphisms of NLRP2 gene were associated with the characteristics of T1DM patients.
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Fulminant type 1 diabetes (FT1D) is a new subtype of type 1 diabetes mellitus.It has a fulminant onset of symptoms accompanied with disturbance of consciousness or elevated trypsin,severe hyperglycemia,and severe metabolic disorders.It is a critical disease.FT1D in pregnant women,the elderly,and children and adolescents have different clinical manifestations and treatments due to their different physiological aspects in comparison with that in the adults.This article summarizes the characteristics and managements of FT1D in pregnant women,the elderly,and children and adolescents in order to further enhance the understanding of FT1 D.We call on all clinicians to be vigilant and pay attention to the early diagnosis and treatment of FT1 D in special populations.
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Objective To explore the association of nocturnal serum cortisol levels with diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus. Methods Serum cortisol levels of 316 overweight or obese type 2 diabetic patients were tested at midnight by the method of chemiluminescence. Diabetic microvascular complications were compared among various groups according to nocturnal serum cortisol levels. All the patients with nocturnal serum cortisol level > 50 nmol/L were asked to undergo overnight low-dose dexamethasone suppression test to rule out the possibility of subclincal Cushing's syndrome. The incidences of diabetic nephropathy ( DN ) , diabetic retinopathy ( DR ) , and diabetic peripheral neuropathy ( DPN ) were examined in all the patients. Results (1)The incidence of DN was gradually increased from 13.3％to 27.7％and 44.2％in patients with low, medium, and high cortisol level groups, showing a statistical difference among 3 groups ( P<0.05) . The incidences of DR in medium and high cortisol level groups were higher than that in low cortisol level group (40.6％and 47.7％vs 22.7％, both P<0.01). The incidence of DPN in high cortisol level group was higher as compared with low cortisol level group (60.5％ vs 38.7％, P<0.01). (2) Nocturnal serum cortisol level in patients with diabetic microvascular complications was higher than that in patients without complications [ (136.87 ± 105.78 vs 97.55 ± 93.48) nmol/L, P<0.01]. Nocturnal serum cortisol level in patients with multiple diabetic microvascular complications was higher than that in patients with single diabetic microvascular complication [ (151.66±114.54vs117.69±90.26)nmol/L,P<0.05].(3)Singlefactorlogisticregressionanalysisshowedthat higher nocturnal serum cortisol level was a risk factor for diabetic microvascular complications in addition to female, age, longer diabetic duration, higher fasting plasma glucose ( FPG ) . Multivariate logistic regression analysis showed that higher nocturnal serum cortisol level was still a risk factor for diabetic microvascular complications after adjusted by diabetic duration, FPG, HbA1C, and the use of insulin (P=0.013). Conclusion Nocturnal serum cortisol level seems to be a risk factor for diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus.