2022年 · 第102卷第16期

Age is a major driver of heterogeneity in type 1 diabetes mellitus (T1DM), with large differences in onset clinical characteristics and laboratory tests among patients in different age groups. Previous studies have shown that changes in metabolism and immune status in patients can be months to years earlier than the onset of diabetes. The TEDDY (The Environmental Determinants of Diabetes in the Young) study explored the heterogeneity of T1DM and the high risk factors of ketoacidosis (DKA) in T1DM patients by analyzing the clinical characteristics of children and adolescents with T1DM at and before onset. A total of 379 children were included in this study, and differences in islet β-cell autoantibody profiles, genetics, family history of diabetes, presence or absence of DKA, symptoms at onset, and adherence to the TEDDY protocol were compared among different age groups of onset (0-4, 5-9, 10-14 years). It was found that higher fasting and postprandial blood glucose, lower fasting insulin and higher blood glucose/insulin ratio were associated with an increased risk of developing T1DM. The incidence of T1DM is related to the number and type of islet autoantibodies, and the incidence of T1DM is highest in patients with multiple antibodies positive; After adjusting for age and family history, it was found that the risk of T1DM was not related to the type of antibody that first appeared (insulin autoantibody or glutamate decarboxylase antibody). Children aged 0 to 4 years had the lowest incidence of T1DM (2.81/1 000 person-years to 4.13/1 000 person-years), lower positive rate of islet β-cell autoantibodies at diagnosis, more severe clinical symptoms, and the highest incidence of DKA. A total of 23 patients experienced DKA (6.1%), with poor compliance in those who experienced DKA, as shown by a longer time interval between the last clinical assessment and confirmation of diagnosis.

In recent years, the development and application of hybrid closed-loop insulin pumps have gradually increased, but their advantages over sensor-enhanced pumps are still unclear, especially for young children with type 1 diabetes. To solve this problem, the researchers randomly recruited children with type 1 diabetes aged 1 to 7 years who were receiving insulin pump therapy in seven centers in Austria, Germany, Luxembourg and the United Kingdom, and conducted a multicenter, randomized, cross-controlled trial. Participants received two treatments in a randomized order over two 16-week treatment periods to compare the therapeutic effects of the closed-loop system with that of the sensor-enhanced pump. The primary observational endpoint was the difference in the percentage of time between the two treatments when blood glucose measurements were in the target range (TIR, 3.9 to 10.0 mmol/L) between the two 16-week treatment periods; Secondary observational endpoints included percentage of time in hyperglycemic state (TAR, blood glucose>10.0 mmol/L), glycosylated hemoglobin level, mean blood glucose level, and percentage of time in hypoglycemic state (TBR, blood glucose<70 mg/dL). A total of 74 participants in the study were randomized with an age of (5.6 ± 1.6) years and a baseline glycated hemoglobin level of 7.3% ± 0.7%. The use of a closed-loop pump increased TIR by 8.7% (95%CI：7.4%~9.9%，P<0.001), TAR decreased by 8.5% (95%CI: 7.1% to 9.9%), glycated hemoglobin decreased by 0.4% (95%CI：0.5%~0.3%）； TBR was similar for both treatments (P=0.74）。 Therefore, this study concluded that the hybrid closed-loop system significantly improved glycemic control in young children with type 1 diabetes compared to the sensor-enhanced pump, and did not increase the risk of hypoglycemia. In the future, further research can be carried out by expanding the sample size to clarify the advantages of hybrid closed-loop insulin pump in young children with type 1 diabetes, and provide evidence for its popularization and application.

Diabetic ketoacidosis (DKA) is a serious and potentially life-threatening complication of diabetes, and adolescents with diabetes are at greater risk of developing DKA. In order to improve the awareness, diagnosis and treatment of juvenile diabetes, the United States launched the Juvenile Diabetes Research (SEARCH) in 2000. Studies have shown that from 2002 to 2010, adolescents with type 1 diabetes (age of diagnosis<The prevalence of DKA was high (about 30%) in 20 years of age), but the trend of change was relatively stable. Due to the changing demographic characteristics of adolescents with type 1 diabetes in recent years, the researchers sought to evaluate the changing trends in the prevalence of DKA among adolescents with type 1 diabetes from 2010 to 2016, and further analyze whether the observed changing trends are related to changes in demographic characteristics. The researchers included a total of 7 612 adolescent patients with type 1 diabetes from 2010 to 2016, calculated the prevalence of DKA within 1 month after being diagnosed with type 1 diabetes each year, and observed the change trend over 7 years to further compare the incidence of DKARRand adjusted after adjusting for demographic characteristics such as age, sex, race, income, education, health insurance status, language, and diagnosis seasonRR。 The results found that the prevalence of DKA among adolescents with type 1 diabetes increased from 35.3% in 2010 to 40.6% in 2016; The prevalence of DKA increases by about 2% annually [RR=1.02（95%CI: 1.01-1.04), adjustedRR=1.02（95%CI：1.01~1.04）； BothP=0.01）］，RRAnd adjustedRRVery similar, indicating that adjustments for demographic characteristics did not materially alter the observed increasing trends; In particular, the prevalence of DKA increased significantly among children aged 10-14 years and males, indicating that this group of people may be at risk for DKA.

The principle of immune checkpoint inhibitors (ICIs) is to restore the immune system's attack on tumors by targeting immune checkpoints on the surface of T cells/tumor cells, and belong to tumor immunotherapy. ICIs treatment induces a variety of immune disorders including type 1 diabetes mellitus (T1DM). ICIS-induced type 1 diabetes mellitus (ICIs-T1DM) is characterized by rapid destruction of beta cells, which can occur as early as 5 d after ICIs treatment. However, the clinical risk factors for ICIs-T1DM and their impact on patient survival remain unknown. Therefore, the researchers used Optum's database to evaluate the incidence and clinical characteristics of tumor patients treated with ICIs between 2017 and 2020. Types of ICIs included in this study include anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) monotherapy, anti-programmed cell death protein-1 (PD-1) /anti-programmed cell death ligand-1 (PD-L1) monotherapy, or anti-CTLA-4 plus anti-PD-1/anti-PD-L1 combination therapy. The Fine-Gray competitive risk model and cause-specific risk model were used to investigate the association between patient/treatment characteristics and ICIs-T1DM. Risk factors included race, age, sex, previous history of other types of diabetes, tumor type, ICIs treatment modality, comorbidity index (CMI), smoking history, and previous history of other immunosuppressive drug use. The effect of ICIs-T1DM on survival was assessed using a Cox proportional hazards regression model and using ICIs-T1DM as a time-varying covariate. It was found that T1DM occurred in 261 (0.86%) of the 30 337 tumor patients receiving ICIs. Compared with anti-PD-1/anti-PD-L1 monotherapy, anti-CTLA-4 plus anti-PD-1/anti-PD-L1 combination therapy increases the risk of T1DM (HR=1.62； 95%CI：1.15~1.26）。 Younger age (every 5 years decrease in ageHRIncrease 1.19,95%CI: 1.13 to 1.25) and previous history of other types of diabetes (HR=4.48； 95%CI: 3.45-5.83) were the risk factors of T1DM induced by ICIs; A history of previous use of other immunosuppressive drugs can reduce the risk of ICIs-T1DM (HR=0.57； 95%CI：0.34~0.95）。 The development of ICIs-T1DM had no statistically significant impact on the survival of cancer patients.

real-time continuous glucose monitoring (rtCGM) has become a key component of intensive insulin regimen therapy and is considered the standard of care for patients with type 1 diabetes (T1DM). There have been few long-term studies to evaluate the efficacy of rtCGM and various insulin injection methods in the past. The research group previously reported the results of the COMISAIR study, which is a 1-year, non-randomized, real-world study that evaluates the long-term use of sensor-augmented insulin regimens (SAIR). In the current 3-year follow-up study, investigators investigated the effects of SAIR interventions on glycemic control and treatment persistence in a larger cohort, aiming to provide further supporting evidence for the use of rtCGM in the management of T1DM.