Volume 102 ·  Issue 16 ·  2022

Diabetes is a group of highly heterogenous diseases with multiple etiopathologies and clinical characteristics. In type 1 diabetes mellitus, there are different endotypes and clinical phenotypes based on genetics, immunology, metabolism and therapeutics. Precision medicine provides novel ideas and strategies for further studies and clinical prevention/control of diabetes. The article summarizes the concepts, progress and future directions of precision medicine for the diagnosis, prevention, treatment, prognosis, and monitoring of diabetes.

Epidemiological survey is a primary measure, following an epidemic detection and report, implemented by agencies for disease control and prevention according to law. It is the key to disposing coronavirus disease 2019 (COVID-19) epidemic and the premise of rapidly controlling this epidemic. In this paper, the essence and fundamental purpose of epidemiological survey in epidemic response was respectively attributed to emergency disposal and epidemic control. Fresh COVID-19 cases experienced by the author were used to introduce "limiting an epidemic to the minimum scale", on-site rapid disposal, developing and verifying a hypothesis, and report writing and suggest some challenges in the survey. This paper highlighted the role of on-site survey that should be not only investigating, but also hypothesizing and, in particular, rapidly disposing. The on-site experience and problems should be particularly transformed into strategies and measures for epidemic prevention and control in time. This paper also emphasized thinking of forming and perfecting the "evidence chain" by systematically checking and laying out the evidence, so as to serve verification of hypotheses. In the face of a once-in-a-century epidemic, extracting the valuable frontline experience of epidemiological survey would be helpful to accurately handle the epidemic situation, maintain the dynamic COVID-zero status, and respond to other major public health events in the future.

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus report on the management of type 1 diabetes in adults in September 2021. The writing group has proposed principles of the diagnosis and management of adult patients with type 1 diabetes, and has made suggestions for glycemic control with individualized glycemic targets to avoid hypoglycemia. They have also emphasized the importance of education and support for the self-management of diabetes in the management of type 1 diabetes.

Type 1 diabetes patients require lifelong dependence on insulin therapy. It is a long-term challenge for patients to effectively deliver exogenous insulin to maintain glucose levels within the individual′s target range as safely as possible for preventing the development and progression of diabetes complications. The management of type 1 diabetes involves multidisciplinary collaboration, referral from different hospitals, and effective diabetes education and management for patients and family members. Compared with the more mature diseases management system in the United States and the United Kindom, the standardized management of type 1 diabetes patients in China started late. Moreover, there are still some difficulties at present. Whereas, with the exploration and efforts of the hospitals at all levels for the management of type 1 diabetes patients, standardization of type 1 diabetes management will gradually step forward and truly realize the lifelong management for patients.

Recently, great progress has been made in the treatment of type 1 diabetes mellitus (T1DM), however the disease still significantly shortens the life expectancy. Cardiovascular complication is the main cause of death in T1DM patients, and the morbidity is even higher than that of type 2 diabetes. The risk factors of cardiovascular complication in T1DM are different from those of type 2 diabetes. Besides hyperglycemia, dyslipidemia, hypertension, microvascular complications and unhealthy lifestyle, non-traditional risk factors also play very important roles in developing cardiovascular complication, such as hypoglycemia, blood glucose variability, insulin resistance, and autoimmune inflammation of heart. At present, there is a lack of risk assessment and prevention measures for cardiovascular complications in T1DM. It is necessary for more studies to explore whether sodium-dependent glucose transporters 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, which can improve cardiovascular and renal outcomes in type 2 diabetes mellitus, can be equally effective in T1DM.

Cavernous vascular malformations (CM), or cavernous hemangiomas, are widely distributed in the central nervous system, soft tissues, and bone. Among them, spinal cord CM is more common in young adults, and the disability rate is high. In order to further standardize the diagnosis and treatment of spinal cord CM, the expert group formulated the Expert Consensus on the Diagnosis and Treatment of Spinal Cord Cavernous Vascular Malformation according to the current status of international and domestic diagnosis and treatment of spinal cord CM. This consensus elaborates and recommends the epidemiology, genetic background, natural course and treatment of spinal cord CM in detail, aiming to provide reference for medical staff who encounter problems in clinical work.

Gastric cancer is one of the most important types of cancer in China. In recent years, the basic research, prevention, screening and diagnosis and treatment of gastric cancer have been greatly improved, and the standardized treatment of gastric cancer has made great progress. Oncology Branch of Chinese Medical Association and Gastric Cancer Professional Committee of Chinese Anti-Cancer Association organized young and middle-aged scholars from general surgery, medical oncology, radiotherapy, endoscopy, pathology, imaging and basic research on gastric cancer to formulate the Guidelines for Clinical Diagnosis and Treatment of Gastric Cancer of Chinese Medical Association (2021 Edition). On the basis of evidence-based medicine, the author draws on the existing international guidelines and expert consensus, draws on the new progress of precision medicine, and timely launches a guide for the diagnosis and treatment of gastric cancer that is suitable for Chinese people, serves clinical practice, and has operational guidance value. The contents of the guidelines cover the prevention, screening, diagnosis, treatment and follow-up of gastric cancer, which will further promote the standardization and individualized diagnosis and treatment of gastric cancer in China.

This study is to investigate the relationship between time in range (TIR) and glucose management indicator (GMI), and the impact of glycemic variability (GV) on their relationship in patients with type 1 diabetes mellitus (T1DM).

The CGM data were collected from a multicenter randomized clinical trial of adults (≥18 years old) with T1DM, including 83 T1DM patients, respectively from the Third Affiliated Hospital of Sun Yat-sen University (72 cases), Drum Tower Hospital Affiliated to Nanjing University School of Medicine (2 cases), and the First Affiliated Hospital of University of Science and Technology of China (9 cases). All subjects wore the iPro^TM2 system for 14 days at baseline (0-2 weeks), 3 months (12-14 weeks), and 6 months (24-26 weeks). Data derived from iPro^TM2 sensor was used to calculate CGM parameters. Correlation between TIR and GMI was explored according to different stratification of glycemic variability assessed by glucose coefficient of variation (CV). Predicted TIR in the fixed GMI value was calculated via the linear regression equations performed in the respective interquartile group of CV.

From November 2017 to June 2021, a total of 233 CGM data were collected with 83 collected from baseline, 80 from the 3-month follow-up, 70 from the 6-month follow-up. Patients including 27 males had a median (Q₁, Q₃) age of 30.69 (25.22, 38.43) years, with a diabetes duration of 10.05(4.46, 13.92) years. The median (Q₁, Q₃) and effective wearing time of available CGM data was 13.92 (13.02, 14.00) days and 91.61% (84.96%, 95.94%), and the value of TIR, GMI and CV was 60.34%±13.03%, 7.14%±0.61% and 41.01%±7.64%, respectively. There was a strong negative correlation between TIR and GMI (r=-0.822, P<0.001). Multiple linear regression analysis showed that the predictive value of TIR calculated from a given GMI was 8.352% higher when CV was up to standard (36%) than that when CV was down to standard. Based on the multiple linear regression equations generated from quartiles of CV, the predicted TIR value was decreased across the ascending quartiles with 69.98 % in the lowest quartile of CV (≤35.91%), 64.57 % in 25^th-50^th quartile of CV (35.91%<CV≤40.08%), 60.96% in 50^th-75^th quartile of CV (40.08%<CV≤45.86%) and 56.44% in the highest quartile of CV (>75^th quartile, CV>45.86%) when GMI was set as 7%.

There is a strong correlation between TIR and GMI in adult patients with T1DM in patients with type 1 diabetes mellitus. CV influenced the relationship between TIR and GMI.

To analyze the changes in glucose after using a decision support system (DSS) of a smartphone mobile application (APP) in adults with type 1 diabetes mellitus (T1DM).

In the intervention study, the data (including general information at the time of registration) of adult T1DM patients enrolled in the Chinese T1DM Registration Management Project and registered with TangTangQuan® APP were collected. Within 1 year after registration, fasting blood glucose, pre-prandial and postprandial blood glucose at the three meals, blood glucose before bedtime and in nocturnal time were collected every 3 months. Frequencies of total recorded glucose values and proportion of different ranges of glycemia were also collected and analyzed, including the range between 3.9-7.8 mmol/L (Euglycemia), ranged below 3.9 mmol/L (Hypoglycemia) and range above 13.9 mmol/L (hyperglycemia). The patients were divided into 3 groups according to the daily use frequency of DSS (Low/Moderate/High frequency groups). The changes in point blood glucose, the proportion of hyperglycemia and hypoglycemia over time were compared among different groups, as well as the baseline characteristics and glucose characteristics of patients.

A total of 629 eligible T1DM patients were included, including 216 (34.3%) males and 413 (65.7%) females, aged (31.5±10.8) years, and disease duration [M(Q₁, Q₃)] of 1.2 (0.1, 7.4) years. There were 239, 189 and 201 patients in the low, moderate and high frequency groups, respectively. Significant differences were observed among the three groups in all timepoints of self-monitoring blood glucose except for the glucose before bedtime from 10 to 12 months after registration (all P values<0.05), and the glucose level at each point in the high frequency group was lower than that in the other two groups. In the first three months after registration, there was no difference in the proportion of hypoglycemia among the three groups (P>0.05). However, from 10 to 12 months after registration, the proportion [M(Q₁, Q₃)] of hypoglycemia [3.34% (0.85%, 7.40%), 3.00% (0.78%, 6.17%), 1.81% (0.37%, 4.69%)] (P=0.022) between groups (from low to high frequency groups) and hyperglycemia [4.04% (0, 12.16%), 1.88% (0, 7.80%), 0.81% (0, 3.87%)] (P=0.001) were significantly different.

The DSS function of mobile APP is helpful to the glucose management of adult patients with T1DM within 1 year after registration. The average blood glucose in adults with T1DM decreased, and the proportions of hyperglycemia and hypoglycemia were also reduced.

To evaluate the effect of TELSA structured education program in adults with type 1 diabetes mellitus (T1DM) in China.

From January 2019 to January 2020, 64 adult T1DM patients who met the standard of entry and had the intention to participate in TELSA structured education program were selected from the outpatient of type 1 diabetes comprehensive management in the Second Xiangya Hospital as intervention group. A total of 64 patients matched by age and sex were enrolled as the control group. During the program, the intervention group lost 3 cases and the control group lost 4 cases. Finally, there were 61 effective samples in the intervention group and 60 effective samples in the control group. The patients in the control group were given face-to-face education by a T1DM educator for about 2 hours. The patients in the intervention group were intervened according to TELSA structured education program. The level of glycosylated hemoglobin, the frequency of hypoglycemia, self-management ability and quality of life were evaluated before intervention, 6 months after intervention and 12 months after intervention.

The ages of the intervention group and the control group were 30.0(22.0,43.5) and 29.5(22.3,42.5) (P>0.05), and the proportions of males were 47.54%(29 cases) and 45.00%(27 cases), respectively (P>0.05). There were interaction effects (P<0.05) on the level of glycosylated hemoglobin, self-management ability and quality of life in the two groups. At 6 and 12 months after intervention of TELSA structured education program, the level of glycosylated hemoglobin in the intervention group decreased from the baseline level (7.87±1.45)% to (7.23±1.06)% and (7.28±0.93)%, respectively, which was significantly lower than that in the control group at 6 months (7.72±1.20)% and at 12 months(7.76±1.24)% (all P<0.05). After TELSA structured education intervention, the scores of self-management scale for adult type 1 diabetes mellitus (SMOD-CA) in the intervention group showed an upward trend (P<0.001), and the scores of diabetes-specific quality of life scale (A-DQOL) showed a downward trend (P<0.001). In contrast, there was no statistically significant difference in the trend of scores in the control group (P=0.853 and 0.227). The comparison between groups at different time points showed that at 6 and 12 months after the intervention, the SMOD-CA scores of the patients in the intervention group were higher than those in the control group (P<0.001), and the A-DQOL scores were lower than those in the control group (P<0.001).

The TELSA structured education program can effectively ameliorate glycemic control, with the improvement of self-management ability and quality of life in adult T1DM patients.

We aimed to investigate the autoimmune status of long-term type 1 diabetes mellitus (T1DM) patients with residual β-cell function.

The residual β-cell function of long-term (disease duration≥10 years) autoimmune T1DM patients from the T1DM Integrated Management Clinic of the Second Xiangya Hospital was assessed by serum C-peptide levels. Patients with fasting or 2-hour postprandial C-peptide levels over the lower sensitivity limit of detection (16.7 pmol/L) were grouped as C-peptide-positive, and others were grouped as C-peptide-negative. We screened and enrolled all the C-peptide-positive patients (n=19). C-peptide-negative patients with matched sex, age, duration, BMI (n=19) and healthy controls (n=19) were recruited at the same time. The frequencies of CD4+T cell (Th1/Th2/Th17/Treg) and B cell (MZB/FoB/B10) subsets, the expression of PD-1/PD-L1 on T and B lymphocytes, and the levels of T1DM related cytokines including IFN-γ, TNF-α, IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-23 and IP-10 were tested. We compared these parameters in patients with different levels of β-cell function.

In healthy controls, C-peptide-negative and C-peptide-positive patients, the frequencies M (Q₁, Q₃) of Th1 cells were 9.93% (7.45%, 15.20%), 14.90% (11.70%, 18.00%) and 10.20% (6.93%, 15.80%) (P=0.015), and the frequencies M (Q₁, Q₃) of Treg cells were 3.52% (2.92%, 5.68%),2.88% (1.64%, 3.22%) and 3.12% (2.81%, 4.81%) (P=0.005), and the frequencies M(Q₁,Q₃) of PD-1+B cells were 4.69% (2.64%, 6.37%), 2.11% (1.45%, 3.63%) and 4.20% (2.53%, 6.01%) (P=0.003), respectively. The levels of IL-6 M(Q₁,Q₃)were 26.43(18.06, 33.35) ng/L, 42.97 (25.52, 66.30) ng/L, and 22.07 (14.85, 34.45) ng/L (P=0.006), and the levels of IP-10 M(Q₁,Q₃) were 107.39 (76.19, 126.07) ng/L, 188.82 (131.27, 348.18) ng/L and 128.26 (114.31, 136.50) ng/L (P<0.001) in healthy controls, C-peptide-negative and C-peptide-positive patients, respectively. Compared with C-peptide-positive patients, the frequency of Th1 cells and the levels of IL-6 and IP-10 cytokines were higher, while the frequencies of Treg cells and PD-1+B cells were lower in C-peptide-negative patients (all P<0.05).

Long-term T1DM patients with residual β-cell function had lower frequency of Th1 cells, lower levels of IL-6, IP-10 cytokines, and higher frequencies of Treg and PD-1+B cells, which indicated a pronounced autoimmune tolerance.

To identify rare variants in exon and exon-intron boundary of containing NLR family CARD domain protein 4 (NLRC4) in type 1 diabetes (T1DM) patients, and to explore their effects on gene function.

A total of 508 T1DM patients and 527 healthy controls in the Department of Metabolic Endocrinology, Second Xiangya Hospital of Central South University from August 2017 to September 2020 were selected. The case group included 264 males and 244 females, and the age [M (Q₁, Q₃)] was [27 (11, 43)] years. The control group included 290 males and 237 females, and their age［M（Q₁，Q₃）］was [47 (36, 60)] years old. Identification of rare variants in exons of NLRC4 gene in T1DM patients and healthy controls was performed and verified by next-generation sequencing and sanger sequencing. The NLRC4 gene wild-type and mutant plasmids were constructed and transfected into 293T cells. Western blot (WB) was used to detect the expression of NLRC4 protein and cleavage products of pro-cysteinyl aspartate specific proteinase(procaspase-1). Cycloheximide (CHX) was added to 293T cells transfected with wild-type or mutant NLRC4 plasmid to detect the degradation of NLRC4 protein. The localization of NLRC4 protein was detected by immunofluorescence, and the concentration of IL-1β in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA).

The sequencing results showed that 4 patients and 2 healthy controls had a heterozygous variant c.208C>T in exon 3 of the NLRC4 gene. Two patient had a heterozygous variant c.1564T>C in exon 4, and 1 patients had c.1219G>C in exon 4. These three variants might be pathogenic variants in T1DM. In 293T cells transfected with NLRC4 wild-type and c.208C>T、c.1564T>C和c.1219G>C mutant plasmids, the expression level, degradation rate, localization of NLRC4 protein and the content of cleavage products of procaspase-1 did not change significantly. However, the concentration of IL-1β secreted by 293T cells transfected with c.1219G>C and c.208C>T plasmid [M(Q₁, Q₃)] was 15.25 (12.98, 17.52) and 15.44 (13.81, 17.07) ng/L, respectively, which was lower than 18.70 (16.59, 20.81) ng/L of 293T cells transfected wild-type plasmid (P=0.020, 0.010).

NLRC4 gene rare variants c.208C>T, c.1564T>C and c.1219G>C may not change the protein expression, degradation and localization, but c.208C>T and c.1219G>C may inhibit the secretion of IL-1β. This result suggests that NLRC4 rare variants may have an impact on gene function.

To investigate the effects of fecal microbiota transplantation (FMT) on non-obese diabetic (NOD) mice of type 1 diabetes mellitus (T1DM) and its underlying mechanisms.

A total of 8-9 week-female NOD mice were randomly divided into control (n=36) and FMT groups (n=36) according to the random number table. Fecal microbiota from C57BL/6 mice were transplanted into FMT group, and control group were transplanted with microbiota from themselves, once every two days for 5 times. The insulitis score and incidence of T1DM were compared between two groups;16S rRNA gene sequencing was used to evaluate the structure of fecal bacteria in NOD mice. The expressions of intestinal barrier related genes were detected by real-time quantitative PCR. The proportions of regulatory T cells (Tregs), helper T cell (Th)-1 and Th17 in the enteric-pancreatic immune axis were detected by flow cytometry. Amino acid in serum was measured by amino acid metabolomics.

Incidence of T1DM in NOD mice from FMT group was 40.9% (9/22), lower than 72.7% (13/22) from control group at 26 weeks of age (P=0.034). FMT promoted colonization of probiotics such as Lactobacillus, Clostridium_sp_ND2, Candidatus_Arthromitus and Clostridiaceae_1; mRNA of intestinal barrier related genes were up-regulated in FMT group [ mucins(Muc)-1: 0.93±0.29 vs 2.97±0.79, P=0.036; Muc2: 0.72±0.39 vs 10.70±3.54, P=0.019;Muc3: 1.79±0.69 vs 10.97±2.78, P=0.009;Muc4: 1.01±0.23 vs 2.42±0.49, P=0.029;Occludin(Ocln): 0.96±0.08 vs 1.81±0.36, P=0.045; Claudin(Cldn)-1:0.94±0.17 vs 2.20±0.43, P=0.022] compared to control. The proportions of Treg in mesenteric lymphoid node, pancreatic lymph node and peyer′s patches of FMT group [(6.10±0.49)% vs (7.54±0.27)%, P=0.020;(5.28±0.39)% vs (6.42±0.34)%, P=0.048;(6.78±0.42)% vs (7.88±0.13)%, P=0.029] were increased compared to control,while proportions of Th1 [(1.02±0.06)% vs (0.83±0.06)%, P=0.040;(0.82±0.10)% vs (0.56±0.05)%, P=0.038;(1.28±0.12) vs (0.85±0.07), P=0.012] and proportions of Th17 [(0.40±0.01)% vs (0.30±0.02)%, P=0.004;(0.40±0.02)% vs (0.31±0.02)%, P=0.008;(0.51±0.06) vs (0.36±0.02), P=0.027] were decreased. The contents of leucine [(92.86±7.32) vs (91.87±12.62) μmol/L, P=0.027], valine [(162.74±15.97) vs (155.89±25.70) μmol/L, P=0.046] and isoleucine [(75.65±5.59) vs (73.61±9.67) μmol/L, P=0.048] in serum were decreased in FMT group.

FMT can alleviate insulitis and T1DM occurrence in NOD mice, of which mechanism may be related to remodeling gut microbiota and improving intestinal barrier function, affecting immune response of enteric-pancreatic immune axis, correcting amino acid metabolism disorder and reducing the accumulation of branch chain amino acids in NOD mice.

Adult occult autoimmune diabetes mellitus (LADA) belongs to an autoimmune subtype of type 1 diabetes mellitus (T1DM), which is often accompanied by autoimmune abnormalities of other organs such as thyroid, parathyroid glands, gonads, and gastrointestinal tract, but rarely complicated by abnormalities of the central nervous system. This paper reports a case of LADA with stiff person syndrome (SPS), and analyzes its diagnosis and treatment process, in order to arouse clinicians' vigilance to T1DM or LADA with SPS.

The incidence of tuberculosis (TB) is high, but primary pancreatic TB is extremely rare and challenging to diagnose. In this paper, a young male patient with pancreatic TB who was misdiagnosed as pancreatic tumor and underwent pancreatic-duodenectomy was reported, and analyzed and discussed in combination with relevant literature reports, in order to further deepen clinicians' understanding of this disease.

Pituitary adenomas are common neuroendocrine tumors. Most of them are benign and have endocrine symptoms, and some of them show invasive growth. Their pathogenesis is not clear yet and the classification system has limited ability to predict the clinical behavior of pituitary adenomas. Epigenetics, the study of alterations in gene expression that do not alter DNA sequences, provides new information for the classification problem of pituitary adenomas and may have implications for prediction and treatment. This paper reviews the research progress of epigenetics of pituitary adenoma.

Type 1 diabetes mellitus (T1DM) is mainly mediated by autoimmune response, and the disruption of homeostasis between intestinal flora and immune system is closely related to the occurrence and development of T1DM. The intervention mode targeting intestinal flora provides a new idea for the disease treatment. At present, animal studies have preliminarily confirmed the protective effect of intestinal flora therapy (probiotic therapy, fecal bacteria transplantation, short chain fatty acid supplementation) on T1DM, but related clinical studies are still in the initial stage, and reasonable and effective treatment options need to be explored. The purpose of this article is to review the progress of intestinal flora therapy in the prevention and treatment of T1DM in animal experiments and clinical studies, and to summarize the current research results and limitations, so as to provide reference for clinical application.

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.