Volume 12 · Issue 12 · 2020

Immune checkpoint inhibitors (ICI) have attracted widespread attention as a new way of tumor immunotherapy. However, while they kill tumors by regulating immune responses, overactivated immune cells may also lead to clinical manifestations such as autoimmunity in multiple systems of the body, that is, immune-related adverse reactions. Although type 1 diabetes is a relatively rare adverse reaction, it is prone to life-threatening diabetic ketoacidosis, and most patients need lifelong dependence on insulin therapy. With the extensive application of ICI in clinical practice, the occurrence of ICI-related type 1 diabetes is bound to be more and more, which should be paid attention to in clinical practice. The author discusses its epidemiological situation, pathogenesis, immunogenetic characteristics, clinical characteristics and clinical management one by one, so as to improve clinicians' understanding.

The combined application of dipeptidyl peptidase 4 (DPP-4) inhibitor and metformin can exert a complementary and synergistic hypoglycemic effect on different pathophysiological defects of type 2 diabetes. DPP-4 inhibitor/metformin fixed dose combination (FDC) has good bioequivalence compared with the free combination of equal dose DPP-4 inhibitor and metformin. Compared with the free combination of two drugs, FDC can simplify treatment regimens and improve patient treatment compliance. The author focuses on the efficacy and safety, advantages and limitations, applicable populations and precautions for use of DPP-4 inhibitor/metformin FDC.

Peripheral artery disease (PAD) increases the risk of amputation and delayed wound healing in patients with diabetic foot ulcers. The guidelines of major international vascular societies include diabetes with PAD in the management of chronic severe limb ischemia (CLTI). Diabetic patients with CLTI are more likely to have tissue loss and infection than patients without diabetes, and the anatomical conditions for vascular reconstruction are poor. The treatment of CLTI in diabetic patients is complex, and clinicians should adopt an integrated management approach based on patient risk assessment, foot pathology severity assessment, and structural anatomical assessment of arterial disease, as recommended by the CLTI Global Vascular Guidelines.

In response to the question of how to better return to walking and moving after healing of foot ulcers in people at high risk of ulcer recurrence, Mueller synthesized available guidelines, evidence, and preventive measures to make 5 recommendations. That is, sustained and slow foot decompression, wearing suitable therapeutic shoes, gradually increasing activity levels, avoiding excessive changes in activity every day and checking both feet every day.

To observe the efficacy and safety of washed microbiota transplantation (WMT) in the treatment of brittle diabetes.

Ten patients with brittle diabetes who were treated in the Department of Endocrinology of Sir Run Run Hospital, Nanjing Medical University from July 2017 to December 2019 were enrolled. After a 4-week run-in period, patients began WMT treatment. At baseline (T0), 1 week post WMT (T1W), 1 month post WMT (T1M), and 3 months post WMT (T3M), the following clinical data were collected: indicators of self-blood glucose monitoring (SMBG), insulin dose, glycated hemoglobin A_1c, blood glucose and C peptide during standard steamed bread meal test, blood lipids, the occurrence of hypoglycemia and adverse events. Continuous glucose monitoring was conducted at T0 and T1W, and diabetes treatment satisfaction questionnaire was conducted at T0 and T1M. Paired t test, Wilcoxon matched-pairs signed rank test, Fisher exact test, One-way analysis of variance (ANOVA) test or Kruskal-Wallis test were used for data analysis.

The insulin dose began to decrease from T1W, with the most significant decrease at T1M (P<0.05). The SMBG showed that the fasting and 2-hour postprandial blood glucose, mean of blood glucose, standard deviation of blood glucose, coefficients of variation of blood glucose values, mean amplitude of glycemic excursions, the largest amplitude of glycemic excursions, episodes of hypoglycemia, low blood glucose index (LBGI) and the mean absolute difference daytime blood glucose after WMT treatment were significantly decreased than T0 (P<0.05). In addition, continuous blood glucose monitoring data showed that the percentage of time with glucose values ≤3.9 mmol/L and the percentage of time with glucose values≥11.1 mmol/L at T1W were significantly reduced compared with T0 [1.46% (0.06%, 3.08%) vs 0 (0, 0.18%), 21.95% (16.02%, 44.68%) vs 5.52% (0.57%, 19.93%), respectively, both P<0.05], while the percentage of time in glucose target range was significantly increased [(44.36±25.24)% vs (74.40±19.13)%,P<0.05]. There was no significant difference in serum C peptide and blood lipid before and after treatment (allP>0.05). No serious adverse events occurred during treatment and follow-up. Up to T3M, the overall effective rate of treatment reached 70% (7/10), with a statistically significant difference compared with T0 (P<0.05 orP<0.01). The total score of WMT treatment satisfaction was significantly increased compared with T0 [(26.0±2.0) vs (18.0±2.0) points,t=9.847, P<0.01].

WMT for the treatment of brittle diabetes is considered to be both safe and efficient with a high patient satisfaction rate.

The aim of the current study is to investigate whether 1, 5-anhydroglucitol (1, 5-AG), glycated albumin (GA) and GA to glycated hemoglobin A_1c (HbA_1c) ratio can be used for early identify fulminant type 1 diabetes mellitus (FT1DM) and type 1A diabetes mellitus (T1ADM).

From January 2007 to July 2018, 20 FT1DM patients and 47 newly diagnosed T1ADM patients (age and sex matched, HbA_1c <8.7%) admitted to the Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People′s Hospital were included in this study. Then, the serum 1, 5-AG, GA, and HbA _1c of these patients were measured for analysis. The 1, 5-AG, GA and GA/HbA_1c ratio between FT1DM and T1ADM patients were compared by the t test and Mann-Whitney U test. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of those indicators in identifying FT1DM and T1ADM with HbA_1c <8.7%.

The FT1DM patients had a decrease trend of 1, 5-AG, although the GA increased slightly comparing with T1ADM patients, the differences was not statistically significant (both P>0.05). However, the GA/HbA_1c ratio in FT1DM patients increased significantly than those in T1ADM patients (P=0.001). The optimal cut-off points for 1, 5-AG and GA identifing FT1DM and T1ADM were 6.2 μg/ml and 17.9%, with their sensitivity up to 95.0% and 90.0% respectively, while the specificity was only 31.9% and 34.0%, and the area under the curve (AUC) was 0.597 and 0.601, respectively. No difference was found in screening efficacy (P=0.972). As for GA/HbA_1c ratio, the optimal cut-off point was 3.187, with its sensitivity, specificity and AUC of 70.0%, 76.6%, and 0.769, respectively. Therefore, GA/HbA_1c was clearly superior to 1, 5-AG or GA alone.

GA/HbA_1c ratio is a better indicator for early identification of FT1DM than 1, 5-AG or GA.

To characterize the biomarkers and immune cell infiltration for glomeruli of diabetic kidney disease (DKD).

Differentially expressed genes (DEG) of glomeruli from in datasets GSE96804 and GSE30528 were identified, and functional enrichment analyses for DEG were performed by using the bioinformatics. Hub genes were extracted as the biomarkers of DKD by module analysis from the protein-protein interaction network (PPI). Receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA) were applied to assess the diagnostic efficiency of Hub genes for DKD. The CIBERSORT algorithm was used to analyze the immune infiltration of glomeruli between DKD group (n=7) and the control group (n=4). The t test was used to compare the difference of gene expression and Wilcoxon test was used to compare the difference of immune infiltration between two groups.

A total of 62 DEG, including 41 downregulated genes and 21 upregulated genes, were detected from the integrated dataset. They were enriched in 52 Gene Ontology terms and 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, we identified ten Hub genes from the PPI network using module analysis, mainly related to extracellular matrix structural constituent, collagen binding, immune cell chemotaxis, extracellular matrix (ECM)-receptor interaction and phosphatidylinositol 3-kinase-serine/threonine-protein kinase (PI3K-Akt) signaling pathway. Consistently, Hub genes showed a predictive effect for DKD by PCA and ROC curve analysis, and the value of area under curve was 0.945, 0.982 and 0.776 in GSE96804, GSE30528 and Merge datasets, respectively. Immune infiltration profiles revealed that compared with normal glomeruli, the glomeruli from DKD contained a higher proportion of M2 macrophages and resting mast cells [(2.77±2.42) % vs (8.68±3.10) %, 0 vs (8.96±7.14) %, both P<0.05].

Hub gene can be used as a biological marker of DKD glomerulopathy, and it has a certain predictive value for DKD. Macrophage infiltration is an important characteristic of DKD.

The role of resveratrol in reducing podocyte damage by regulating autophagy in the kidney of mice with type 1 diabetes mellitus.

A total of 28 healthy male Kunming mice without specific pathogen were selected, of which eight healthy Kunming mice were included in normal control group (NC group). The remaining twenty Kunming mice were given streptozotocin to establish the model of type 1 diabetes mellitus. Eighteen mice successfully induced with diabetes were randomized into diabetes mellitus group (DM group, n=9) and resveratrol intervention group (Res group, n=9). At the end of the 12th week, the urine was collected to detect 24-hour urine protein, and the serum was used to detect creatinine and urea nitrogen. Real-time fluorescent quantitative polymerase chain reaction and Western blotting method were used to detect the expression levels of silent information regulator 1 (SIRT1), forkhead transcription factor O1 (FoxO1), microtubule-associated protein 1 light chain 3 (LC3) Ⅱ, P62, nephrin, podocin and phosphorylation of FoxO1 (p-FoxO1)/FoxO1. Immunohistochemistry was used to observe the expression levels of nephrin and podocin in podocytes. The morphology and ultrastructure of glomerular were observed by Hematoxylin-eosin staining and the method of electron microscopy. Analysis of variance was used for comparison in multiple groups. LSD-t method was used for comparison between two groups.

Compared with NC group, the level of plasma creatinine, plasma urea nitrogen and 24-hour urine protein in DM group were increased (t=-39.57, -28.17, -57.31, all P<0.05). The expression levels of SIRT1, LC3Ⅱ, nephrin and podocin were decreased, where as the expression level of P62 was increased in DM group compared with NC group (allP<0.05) The ratio of p-FoxO1/FoxO1 was also increased in DM group (0.71±0.03 vs 0.32±0.01,t=-38.81, P<0.05). Results from light microscope and electron microscope showed that the glomerulus, basement membrane and podocyte structures were damaged. Compared with DM group, plasma creatinine, plasma urea nitrogen and 24-hour urine protein in Res group were decreased (t=30.89, 16.39, 49.64, all P<0.05). In Res group, the expression levels of SIRT1, LC3Ⅱ, nephrin and podocin were increased, but the expression level of P62 were decreased compared with DM group (allP<0.05). Beside, resveratrol treatment also decreased the ratio of p-FoxO1/FoxO1 (0.42±0.01 vs 0.71±0.03,t=27.47, P<0.05). Results from light and electron microscopy showed that above damages were reduced.

Resveratrol protects podocytes by activating SIRT1/FoxO1 pathway and increasing the level of autophagy in the kidney in mice with diabetes mellitus.

To evaluate the efficacy and safety of recombinant insulin lispro (produced by Jiangsu Wanbang Biopharmaceuticals) in the patients with diabetes mellitus.

A multi-center (29 hospitals), randomized, and positive parallel controlled clinical trial was carried out from November 2017 to November 2019. Six hundred and twenty six patients with diabetes duration longer than 6 months, only oral antidiabetics (OAD) therapy or OAD combined with insulin therapy or only insulin therapy (≥twice per day) stabilized for more than 3 months, 7.5%≤ hemoglobin A1c (HbA_1c) ≤13.0% were selected and randomly assigned to observation group (n=315) and control group (n=311) according to the ratio of 1∶1 (block randomization). The two groups were given recombinant insulin lispro (observation group, n=315) or insulin lispro (control group, n=310, 1 case was rejected) injection once before each meal, both on the basis of injection of recombinant insulin glargine once daily. The change in HbA_1c, blood glucose, lipid levels, body weight, insulin autoantibody (IAA) and incidence of adverse events after 16 weeks was compared. The t test, t′ test, chi-square test or Fisher exact probability test were used for comparison between groups and paired t test was used for intra-group comparison.

After 16-week of treatment, HbA1c reduced (1.18±1.26)% and (1.41±1.30)% from baseline respectively in observation group and control group, with non-inferiority found in observation group as compared with control group using analysis of variance (ANOVA) model (F=2.81, P>0.05, one-side 97.5%CI: -0.14(-0.30, ∞). There was no statistically significant difference in reduction of FPG and 2hPG from baseline to the 16th week between two groups (P>0.05). There was no statistically significant differences in change of triglyceride, total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol levels from baseline to the 16th week between two groups (P>0.05). There was no statistically significant differences in change of body weight and IAA from baseline to the 16th week between two groups (P>0.05). There was no statistically significant differences in the rate of hypoglycemia events or other adverse events between two groups (P>0.05).

The domestic recombinant insulin lispro is non-inferiorto imported insulin lispro in the terms of efficacy. The safety and changes of lipid level, body weight, IAA of domestic recombinant insulin lispro are consistent with imported insulin lispro.

To explore predictive model for gestational diabetes mellitus (GDM) and develop a Risk Score to predict the risk of GDM early.

The medical records of 1 150 normal glucose tolerance (NGT) and GDM pregnant women in Nanjing Drum Tower Hospital from January 2015 to May 2017 were analyzed retrospectively as the training cohort, and logistic regression analysis was used to establish early predictive model for GDM and develop GDM Risk Score. Then the medical records of 490 pregnant women with NGT and GDM from June 2017 to June 2018 were analyzed as the validation cohort, and receiver operator characteristics (ROC) curve as well as Hosmer-Lemeshow test was used to verify the effectiveness of GDM Risk Score.

(1) For the training cohort, the early prediction model of GDM consists of the GDM Risk Score during first trimester and 14 to 20 gestational weeks, including pregnant women age, height, pre-pregnancy body mass index, education background, family history of diabetes, menstrual history, history of cesarean delivery, GDM, polycystic ovary syndrome and hypertension, fasting plasma glucose (FPG) during first trimester, FPG and triglycerides during 14 to 20 gestational weeks amount to 13. (2) For the validation cohort, according to the ROC curve, the area under the curve (AUC) of the Risk Score during first trimester was 0.781 (95%CI 0.735 to 0.828), which increased to 0.850 (95%CI 0.811 to 0.889) after supplementing Risk Score during 14 to 20 gestational weeks; it was found that the model of GDM Risk Score during first trimester and 14 to 20 gestational weeks fit well through Hosmer-Lemeshow test.

The GDM Risk Score based on risk factors of GDM appears to be a reliable screening tool to detect the risk of GDM earlier.

To investigate the relationship between serum C1q/tumor necrosis factor related protein 12 (CTRP12) with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).

From March 2019 to June 2020, patients with newly diagnosed T2DM and age- and sex-matched people with normal glucose tolerance (NGT) were selected respectively from the First Affiliated Hospital of Soochow University. The subjects were divided into four groups according to the results of ultrasound images: people with T2DM but without NAFLD was assigned to T2DM group, with T2DM and NAFLD assigned to T2DM+NAFLD group; the rest people with normal glucose tolerance (NGT) were divided into NGT group and NGT+NAFLD group according to without or with NAFFLD. Clinical data were collected and serum CTRP12 concentration was detected by enzyme-linked immuno sorbent assay (ELISA). Pearson correlation was used to analyze the correlation between CTRP12 and other variables, and binary logistic regression was used to analyze the independent influencing factors of NAFLD.

One hundred and twenty five patients with newly diagnosed T2DM and 121 people with NGT were enrolled respectively: people with T2DM but without NAFLD was assigned to T2DM group (n=55), with T2DM and NAFLD assigned to T2DM+NAFLD group (n=70), NGT group (n=74) and NGT+NAFLD group (n=47). The level of serum CTRP12 was the highest in NGT+NAFLD group [(338.58±68.66) pg/ml], and the lowest in T2DM group [(264.57±56.65) pg/ml]. There was no difference between serum CTRP12 in NGT group and T2DM+NAFLD group (P>0.05). Serum CTRP12 was negatively correlated with fasting plasms glucose (FPG), glycated hemoglobin (HbA_1c), fasting insulin (FIN), insulin resistance (HOMA-IR) (r=-0.248, -0.338, -0.274 and -0.302, respectively; P<0.01). Binary logistic regression showed that CTRP12, waist circumference (WC), alanine aminotransferase (ALT), triglyceride (TG) were independent risk factors of NAFLD (P<0.01).

Serum CTRP12 decreases in people with T2DM. The increase of CTRP12 might be an independent risk factor of NAFLD.

To investigate the effect of glycated hemoglobin A_1c (HbA_1c) variability on diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.

A total of 3 133 T2DM patients without DKD at baseline were selected from Lee′s United Clinic (6 centers) in Taiwan, China from 2002 to 2014 using the convenience sampling method. The patients were divided into DKD group (n=1 152) and non-DKD group (NDKD, n=1 981) according to the presence or absence of DKD at follow-up. The age, body mass index (BMI), waist hip rate (WHR), duration of diabetes, medication, blood pressure, lipid profiles, HbA_1c and other clinical data of all patients were collected. HbA_1c variability was expressed as HbA_1c standard deviation (HbA_1c-SD). The mean value (HbA_1c-Mean) and standard deviation were calculated based on the values of HbA_1c recorded by all patients. Then, all participants were divided into four groups according to the HbA_1c mean value above or below the target value by 7% and the HbA_1c standard deviation above or below the population mean by 0.48%: Q₁ group (HbA_1c-Mean<7%, HbA_1c-SD<0.48%);Q₂ group (HbA_1c-Mean<7%, HbA_1c-SD≥0.48%); Q₃ group (HbA_1c-Mean≥7%, HbA_1c-SD<0.48%) andQ₄ group (HbA_1c-Mean≥7%, HbA_1c-SD≥0.48%). The differences of the above indicators among each group were compared using independent sample t test, nonparametric test and χ² test. Cox regression analysis was used to analyze the relationship between HbA_1c variability and DKD.

The age, BMI, diabetes duration, the use of angiotensin converting enzyme inhibitor/angiotensin Ⅱ receptor blocker in proportion to the blood pressure medication, HbA_1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), and serum creatinine (Scr) in DKD group were higher than those in NDKD group. However, high-density lipoprotein-cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) and the proportion of the combined diabetic retinopathy were lower in DKD group than those in NDKD group (all P<0.05). Cox regression revealed that HbA_1c variability is an independent risk factor for DKD after adjusting for age, sex and diabetes duration [hazard ratio (HR)=1.240,P<0.01]. Further stratification analysis revealed that patients inQ₄ group had the highest DKD prevalence (HR=1.601, P<0.01)whileQ₁ group had the lowest. In addition, patients inQ₂ group (HR=1.424, P<0.01) had a higher risk of DKD than those inQ₃ group (HR=1.184, P<0.01). Adjusted for age, sex, diabetes duration, BMI, WHR, SBP, DBP, TC, TG, low-density lipoprotein-cholesterol and HDL-C, patients inQ₄ group had the highest risk of eGFR reduction (HR=1.230, P<0.01) whileQ₁ group had the lowest. Patients in Q₂ group (HR=1.161, P=0.023) had a higher risk of eGFR reduction than those in Q₃ group (HR=1.124, P=0.012).

HbA_1c variability is an independent predictor of DKD in T2DM patients compared with the mean HbA_1c, HbA_1c variability contributes to DKD development when the mean of HbA_1c variability is over 0.48%.

To explore the association of glomerular deposition of complement C3c and C1q with baseline clinicopathological characteristics and the prognosis of type 2 diabetic patients with diabetic kidney disease (DKD).

A total of 112 patients with DKD diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2011 to July 2019 were recruited in this study. Among them, 83 patients (74.1%) were males. The average age were (51.22±11.12) years with 19.0 (8.5, 31.3) months of follow-up. According to the glomerular deposition of C1q and C3c, all patients were divided into four groups: C1q non-deposited and C3c non-deposited group (n=38), C1q non-deposited but C3c deposited group (n=24), C1q deposited but C3c non-deposited group (n=14) and C1q deposited and C3c deposited group (n=36). Clinical indicators such as 24 h urine protein were detected and pathological data were collected. Cox regression and Kaplan-Meier survival curve were used to evaluate the effect of renal C1q and C3c deposition on renal prognosis.

There were significant differences of 24 h urine protein among the four groups [1.84 (0.92, 3.89), 4.19 (2.09, 6.50), 3.30 (1.84, 6.70), 3.64 (2.49, 7.22) g/24 h, respectively,P<0.01]. The 24 h urine protein in C1q deposited and C3c deposited group was significantly higher than that in C1q non-deposited and C3c non-deposited group (P<0.01). Kaplan-Meier survival curve results showed that the cumulative survival rates of the four groups were statistically different (Log-rank χ²=8.785, P<0.05), and C1q deposited but C3c non-deposited group had the lowest cumulative survival rate and the worst prognosis. Adjusted multivariate Cox analysis showed that both the co-deposition of glomerular C1q and C3c (hazard ratio=2.260, 95% confidence interval was 1.329-3.845,P<0.05) and glomerular C1q+C3c+IgM (hazard ratio=4.142, 95% confidence interval was 1.071-16.021,P<0.05) were independent risk factors for renal prognosis.

Glomerular C3c and C1q deposition are associated with deteriorated renal function and prognosis in patients with DKD. Glomerular C1q and C3c co-deposition is an independent risk factor for DKD progression.

To explore the association between bulimia nervosa and type 2 diabetes, this paper performed a meta-analysis by searching the literature of cohort studies and case-control studies associated with bulimia nervosa and type 2 diabetes outcomes, with a time limit of January 2020. Literature screening, data extraction and quality evaluation were performed according to inclusion and exclusion criteria. CMA v2 software was applied for meta-analysis. There were ultimately 7 observational studies (n=19 240) into this analysis, 3 were cohort studies and 4 were case-control studies. Cohort study meta-analysis results showed that bulimia nervosa patients had a higher risk of developing type 2 diabetes than non-bulimia nervosa patients [relative risk =2.09 (95% confidence interval 1.64-2.68),P<0.001］； Case-control study meta-analysis results also confirmed that bulimia nervosa increases the risk of developing type 2 diabetes in adults [odds ratio =2.85 (95% confidence interval 2.20-3.69),P<0.001］。 Therefore, we conclude that bulimia nervosa is a risk factor for type 2 diabetes and is strongly associated with type 2 diabetes.

The diagnosis and treatment of a 41-year-old woman with fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome was retrospectively analyzed, and the relevant literature was reviewed, aiming at improving the understanding of related diseases.

A 76-year-old female patient with diabetic foot underwent regular hemodialysis through right internal jugular vein subcutaneous tunnel CUFF catheter for chronic kidney disease. Echocardiography, CT cardiac three-dimensional reconstruction enhanced scan and MRI cardiac function enhanced scan showed right atrial mass occupation, and the diagnosis of hemodialysis catheter related right atrial thrombosis (CRAT). After 4.5 months of vasodilator, anti-platelet aggregation and anticoagulant therapy, the thrombus was significantly reduced, and the CUFF catheter was replaced. Postoperative follow-up patients were generally in good condition. For diabetic patients complicated with chronic kidney disease, patients with podiatry who undergo CUFF catheter insertion and regular hemodialysis should be alert to the occurrence of CRAT.

The onset, clinical manifestations, diagnosis and treatment, outcome and prognosis of a 73-year-old male patient with Fusarium infection after antibacterial treatment of diabetic foot were reported.

A patient with polycystic ovary syndrome (PCOS) with increased blood glucose during pregnancy after assisted reproduction was reported. After threatened abortion, dexamethasone was given to promote fetal lung maturation and then progressed to diabetic ketoacidosis (DKA). Postpartum glucose tolerance returned to normal, suggesting that timely and reasonable treatment can have better outcome and prognosis.

This paper reports the clinical diagnosis and treatment of 2 patients with diabetic radiculoplexus neuropathy (DRPN), and reviews the literature to summarize the characteristics of this rare diabetic neurological complication, so as to strengthen the clinical identification of this kind of disease. Both cases were acute or subacute onset, with unilateral proximal lower limb pain as the first symptom, and the lesion gradually extended to the distal, contralateral or chest and abdomen of the lower limb, accompanied by proximal muscle atrophy, decreased muscle strength, and inability to walk on their own. The effect of conventional treatment was not good, and glucocorticoids were used in both cases, and immunoglobulins were combined in one case. Literature review suggests that the possibility of DRPN should be considered when severe pain is unilateral, mainly proximal to the limb, accompanied by unilateral, proximal muscle weakness and muscle atrophy. The diagnosis of DRPN is mainly based on clinical symptoms, signs, laboratory tests, electrophysiology, etc., and the causes such as structural and non-structural damage of nerve roots should be excluded. At present, there is no specific treatment for DRPN, mainly basic treatment of diabetes, immunotherapy, analgesia, rehabilitation training, psychological counseling, etc. When diabetic patients have atypical and unilateral proximal limb pain, muscle weakness, muscle atrophy and other clinical manifestations, the possibility of DRPN should be considered to avoid delaying diagnosis and treatment.

A retrospective review of mitochondrial tRNA in a case of seizure onset^{Leu (UUR)}Diabetes mellitus with A3243G gene mutation. The disease is characterized by maternal inheritance, elevated blood sugar, and mostly accompanied by hearing impairment. It can be combined with systemic and multisystem diseases, and has a genetic tendency. If clinical diagnosis and treatment are not treated in time, it can lead to family aggregation. Clinicians should improve their understanding of this disease, recognize it early, and do a good job in eugenic supervision.

Complications of cardiovascular disease are one of the main causes of death in diabetic patients. Studies have shown that interventions for traditional cardiovascular risk factors such as hyperglycemia, high-low-density lipoprotein cholesterol, hypertension, diabetic nephropathy, and poor lifestyle do not significantly reduce mortality in patients with type 1 diabetes (T1DM). In recent years, several studies have explored new risk factors associated with cardiovascular complications of T1DM, including blood glucose fluctuations, hypoglycemia, insulin resistance, severe diabetic retinopathy, cardiac autoimmunity, and depressive states. How to early diagnose and intervene the risk factors related to cardiovascular complications is an important issue in the management of cardiovascular complications in T1DM.

Monitoring islet β cell death is helpful to deeply understand the pathogenesis of type 1 diabetes mellitus (T1DM), but there is still a lack of non-invasive methods to directly reflect β cell death in clinic. Circulating unmethylated insulin (UINS) DNA can act as a specific marker of beta cell death. Studies have shown that the circulating UINS DNA has increased several years before the onset of T1DM high-risk people and several weeks before the onset of non-obese diabetic mice, and the circulating UINS DNA of newly diagnosed and long-course T1DM patients has also increased to varying degrees, reflecting the occurrence of β cell death in different stages of T1DM patients. Circulating UINS DNA is also valuable in the monitoring of β cell death after islet transplantation, prediction of long-term effect, and evaluation of immunotherapy effect of T1DM. With the deepening of research, the application value of circulating UINS DNA as a marker of β cell death in other types of diabetes and related diseases has also begun to receive preliminary attention, and more β cell-specific non-methylated DNA has also been discovered. However, current limitations and controversies in detection methods, specificity of methylation sites, stability of methylation patterns, quantitative standards, index half-lives, etc. bring challenges to the research and application of circulating UINS DNA.

Histone acetylation is an important epigenetic regulation mode, which is influenced by cellular energy metabolism and can regulate cellular metabolism. It participates in β cell development and apoptosis, insulin resistance and inflammatory response, and plays an important role in the occurrence and development of diabetes mellitus and its complications. At present, there have been studies aimed at this target to explore the treatment of diabetes, but it is still in the initial stage.

Epigenetic changes adapted to environmental stimuli may play an important role in the pathogenesis of diabetes mellitus, and N6-methyladenosine (m6A) is one of the most representative reversible mRNA methylation modifications. m6A plays an important regulatory role in the cell cycle and insulin secretion of islet beta cells by influencing the insulin/insulin-like growth factor 1-protein kinase B-islet duodenal homeobox 1 signaling pathway. This paper reviews the research status and development trend of m6A and its methylation regulatory proteins on the function of diabetic pancreatic islet β cells in recent years.

As a highly heterogeneous special group of elderly diabetic patients, in addition to the risk of death caused by complications or blood sugar fluctuations, cognition and somatic function are also two important indicators affecting death. Frailty is an aging-related geriatric syndrome that is mainly characterized by decreased physiological reserve and function, associated with adverse outcomes such as disability, falls, and death. Many studies have found that cognitive dysfunction and weakness often coexist in the elderly population, and both are closely related to diabetes. The interaction of cognitive impairment and debilitation accelerates cognitive and somatic decline, severely affecting prognosis in older patients with diabetes.

As diabetic cardiomyopathy (DCM) progresses, it will eventually lead to heart failure, arrhythmia, and even sudden death. The oxygen-linked N-acetylglucosamine (O-GlcNAc) glycosylation modification of the protein is involved in the progression of DCM myocardial injury and heart failure by affecting various mechanisms such as energy metabolism, oxidative stress, cardiomyocyte apoptosis, and autophagy in the mitochondria. The authors focused on the dynamic regulation process and biological function of O-glycosylation modification and its role in the progression of DCM.

In autumn Beijing, the whole city exudes intoxicating ancient charm. More than 100 editorial board members and corresponding editorial board members of Chinese Diabetes Journal gathered in Beijing on September 25, 2020, and held the first plenary meeting of the third editorial board of the magazine. Wei Junmin, president and editor-in-chief of Chinese Medical Association Magazine, and Bao Yalin, editor and editor of Chinese Medical Association Journal Management Department, attended the meeting.