Volume 14 · Issue 06 · 2022

Metformin has been consistently recommended by domestic and foreign guidelines as the drug of choice for the treatment of type 2 diabetes based on previous efficacy, safety and health economics data. However, in the process of long-term treatment with metformin, some patients may develop vitamin B12 deficiency, which may lead to complications such as megaloblastic anemia, cognitive impairment, and peripheral neuropathy, which seriously affect the health of patients. This article focuses on the research progress of the relationship between metformin use and vitamin B12 level in diabetic patients, aiming to provide reference for early assessment of serum vitamin B12 status in patients using metformin, early detection of complications caused by it, and early intervention.

The defect of islet β cell function is one of the basic pathophysiological characteristics of type 2 diabetes mellitus. Correct evaluation of islet β cell function is of great value for the diagnosis, classification and treatment of diabetes mellitus. Protection of islet β cell function has important clinical significance for delaying the progression of type 2 diabetes mellitus. Therefore, the islet beta cytology group of the Diabetes Branch of the Chinese Medical Association and the Endocrinology Branch of Jiangsu Medical Association organized experts to write the "Clinical Expert Consensus on the Function Assessment and Protection of Islet beta cells in Type 2 Diabetes Mellitus". This consensus proposes that clinically, pancreatic islet β cell function can be evaluated by simple blood glucose-based methods, or combined with blood glucose, endogenous insulin, and C peptide detection methods; It is emphasized that metabolic indicators such as weight loss, early intervention and long-lasting and stable control of blood sugar can effectively protect the function of pancreatic islet β cells, and some drugs may also have the effect of improving the function of pancreatic islet β cells in addition to hypoglycemia.

Combined with domestic and foreign guidelines and clinical practice, this paper excerpts and interprets the decompression treatment of diabetic foot, so as to better choose and apply this treatment method in clinical work. In the process of decompression diagnosis and treatment, it is necessary to comprehensively evaluate the effectiveness, safety and patient compliance of these decompression treatments, master the application value and limitations of decompression methods, and carry out decompression treatment scientifically and reasonably.

To analyze the effects of risk of obstructive sleep apnea hypopnea syndrome (OSAHS) and anxiety on diabetes mellitus (DM) and their interaction.

Inpatients in Beijing Hospital from July 2019 to July 2020 were include in the cross-sectional study. Berlin Questionnaire and Generalized Anxiety Scale were used to evaluate OSAHS risk and anxiety status of these inpatients. The chi-square test and non-parametric test were used to compare the difference of OSAHS risk and anxiety among inpatients with different blood glucose status. Logistic regression analysis was used to analyze the influence of OSAHS risk and anxiety on DM. Delta method was used to calculate the interaction between OSAHS risk and anxiety on DM.

There were 1 030 residents involved in the final analysis, among which the constituent ratio of DM was 24.1%. After adjusting for age, gender, body mass index (BMI), smoking and drinking history and complications, OSAHS risk (OR=1.592, 95%CI 1.155-2.196, P=0.005) and anxiety (OR=1.531, 95%CI 1.059-2.215, P=0.024) were independently associated with DM respectively. After adjusting for confounding factors, OR value of OSAHS risk multiplied by anxiety for diabetes was 0.702 (95%CI 0.344-1.433, P=0.331). Compared with patients who had low risk of OSAHS and no anxiety symptoms, the risk of DM in those with high risk of OSAHS but without anxiety was 1.729 (95%CI 1.205-2.482, P=0.003), and the risk of DM in those with low risk of OSAHS and anxiety was 1.794 (95%CI 1.108-2.904, P=0.018). The risk of DM in those with high risk of OSAHS and anxiety was 2.176 (95%CI 1.299-3.646, P=0.003).

The prevalence of DM in inpatients was high. The high risk of OSAHS and anxiety were independently related to DM, and there was no multiplicative or additive interaction between OSAHS risk and anxiety on DM.

To investigate the effects of once-weekly dulaglutide 1.5 mg treatment on glucose variability and glucose control in type 2 diabetes patients using 24 h continuous glucose monitoring (CGM) technology.

A multi-center, prospective study was carried out. A total of 149 type 2 diabetes patients were recruited, who were treated with dulaglutide for 2 to 4 weeks, wearing CGM devices to monitor the glucose level. The primary evaluation indicators included mean amplitude of glycemic excursions (MAGE), mean daily glucose (MDG), time in target glucose range (TIR), time above range and time below range (TAR, TBR). Secondary indicators included change of concomitant medication dosages, treatment-related adverse events and change of blood pressure. Mixed effects model (MEM) of repeated measurement data or paired Mann-Whitney rank-sum test was used to analysis the differences between CGM parameters in each week during the treatment period.

MDG and MAGE of patients decreased by (0.76±0.31) and (0.50±0.13) mmol/L (P<0.05), respectively, after the 4-week dulaglutide treatment. When compared with the first week, time in range (TIR) in week 2 increased from 73.91% (IQR 25.20%) to 7.49% (IQR 24.89%), and the mean difference was 3.58% (P<0.01). Time in hyperglycemia decreased from 2.95% (IQR 10.76%) to 1.94% (IQR 7.24%), and the median difference was 1.01% (P<0.001), while the time in hypoglycemia did not change (P>0.05). Mean systolic pressure of patients decreased by (5.2±1.5) mmHg (1 mmHg=0.133 kPa) after the first-week treatment. Furthermore, 14 patients reported treatment-related adverse events including gastrointestinal reaction and hypoglycemia.

Treatment with dulaglutide 1.5 mg weekly for 2 to 4 weeks could significantly reduce glycemic variability, improve short-term glucose control and lower blood pressure in type 2 diabetes patients without significantly increasing the risk of hypoglycemic events.

To explore the latest development of clinical trials of diabetes drugs in China from 2019 to 2021.

Information based on the platforms for drug clinical trial registration and information and accepted variety catalog registration information of Center for Drug Evaluation (http://www.chinadrugtrials.org.cn/). Extracting the information of clinical trials of diabetes drugs during 2019 to 2021, including basic information, management information, the scope and stage of the trial, type of the sponsor and drugs.Chi-square was used to compare the counting data between domestic and foreign pharmaceutical enterprises.

Five hundred and eighty nine clinical trials of diabetes drugs registered in China during 2019 to 2021, accounted for 7.36% (589/8 002) of all varieties. From the scope of trials, domestic trials accounted for 96.26%(567/589), international multi-center trials taked up 3.74% (22/589). From the type of sponsors, domestic pharmaceutical companies initiated 542 (92.02%) and among which, global pharmaceutical companies initiated 47 (7.98%). Analyze by the phase of the trials, the bioequivalence test was 50.76% (299/589), the phase Ⅰ clinical trial was 29.54% (174/589), and the phase 2 and 3 trials were 19.00% (112/589). From the perspective of the type of the drugs, innovative drugs were the most common type of drugs (34.13%, 201/589), generic drugs accounted for 26.66% (157/589) and imported medicine occupied 6.11% (36/589). According to registration classification were divided into chemical drugs (77.42%, 456/589), biological products (21.22%, 125/589) and traditional chinese medicine/natural medicine (1.36%, 8/589). The main focus in terms of the type of drug being tested was dipeptidyl peptidase Ⅳ inhibitor (105/589, 17.83%), glucagon-like peptide-1 receptor agonist (65/589, 11.04%), sodium-glucose cotransporter 2 inhibitor (64/589, 10.87%), insulin and insulin analogues (53/589, 9.00%), compound preparations (49/589, 8.32%) and metformin (48/589, 8.15%).

There are a large number of diabetes clinical drug trials in my country from 2019 to 2021, and the innovation of new drug research and development has been greatly improved. Some multinational companies are introducing early research on new drugs into China actively.

To establish a visualization tool for evaluating on risk prediction of peripheral vascular disease (PAD) in patients with type 2 diabetes mellitus (T2DM).

A retrospective analysis of 1 851 T2DM patients treated in Shijiazhuang Second Hospital during December 2017 to August 2020 were randomly sampled into training set (1 389 cases) and validation set (462 cases) by a ratio of 3∶1. General subject data, physical examination indicators, and biochemical indicators were collected. The collected data was used to assess the risk of T2DM combined with PAD. In order to construct a nomogram model to predict PAD risk in T2DM patients, LASSO regression analysis and cross-validation were used to screen the best predictors by RStudio software, and then multivariate logistic regression was used to introduce the predictors selected from LASSO regression. Receiver operating characteristic (ROC) curve, correction and decision curve were used to evaluate the efficacy of the model.

In training set, the results of the LASSO combined with the logistic regression analysis showed that age (OR=1.034, 95%CI 1.020-1.047), smoking (OR=2.363, 95%CI 1.720-2.804), drinking (OR=3.692, 95%CI 2.618-5.230), duration of diabetes (OR=1.040, 95%CI 1.006-1.076), systolic blood pressure (OR=1.026, 95%CI 1.014-1.039), high-density lipoprotein-cholesterol (OR=0.467, 95%CI 0.276-0.779), low-density lipoprotein-cholesterol (OR=1.459, 95%CI 1.239-1.721), white blood cell count (OR=1.137, 95%CI 1.027-1.260), platelet distribution width (OR=1.285, 95%CI 1.202-1.375), large-platelet ratio (OR=0.911, 95%CI 0.890-0.931), and the use of antihypertensive drugs (OR=0.422, 95%CI 0.322-0.551) were the influencing factors of T2DM with PAD, and all differences were statistically significant (P<0.001). The area under curve (AUC), sensitivity, and specificity of the training and validation sets for predicting the occurrence of PAD in patients with T2DM were 0.819 (95%CI 0.796-0.842, P<0.001), 70.5%, 82.9%, and 0.821 (95%CI 0.779-0.862, P<0.001), 78.3%, and 75.4%, respectively. The clinical decision curve showed that the net gain for predicting the risk of PAD onset in T2DM was higher when the PAD risk threshold probability was between 31% and 81%, 37% and 94%, respectively.

This study successfully constructed a practical nomogram model with high accuracy and excellent performance to predict the risk of PAD onset in T2DM patients.

To investigate the effects of portable and wearable devices combined with exercise management on blood glucose and muscle oxygen metabolism in type 2 diabetes mellitus (T2DM) patients.

A total of 54 T2DM patients without exercise contraindications, who were admitted to the Department of Endocrinology in the First Affiliated Hospital of Henan University of Science and Technology from May 2018 to June 2019 were selected. The patients were divided into two groups: wearable devices combined with the exercise management group (the experimental group, 33 cases) and control group (21 cases) according to the random envelope method. Both groups were given routine discharge health education and exercise guidance. The experimental group wore portable devices during exercise once every other day for two weeks. Two weeks later, a home program with brisk walking according to the exercise speed of the patients was formulated, and the program was managed remotely through step counting on Wechat, the daily exercise of patients was uploaded to the Wechat group of exercise management. After 24 weeks, the patients were tested in the exercise center. The control group wore portable devices to collect indicators at baseline and the end of the study, without exercise intervention guidance. After 24 weeks, the changes of the two groups in fasting plasma glucose (FPG), glycated hemoglobin A_1c (HbA_1c), low-density lipoprotein cholesterol (LDL-C), muscle oxygen, and heart rate were measured. Statistical analysis to compare the indexes between groups was conducted with t-test, Wilcoxon rank-sum test, or χ² test.

Compared with the control group, LDL-C significantly decreased in the experimental group [(-1.02±0.96) vs. (0.19±0.85) mmol/L, respectively, P<0.05] after the intervention. In contrast with the indexes before intervention, FPG [7.00 (5.90, 8.20) vs. 8.00 (6.70, 9.60) mmol/L], HbA_1c [6.40% (6.10%, 7.00%) vs. 7.50% (6.20%, 10.10%)] and LDL-C [(1.83±0.72) vs. (2.85±0.80) mmol/L] in experimental group decreased significantly (P<0.05). The crossing time of muscle oxygen and heart rate curve, the lowest point time of muscle oxygen, and the rising point time of muscle oxygen were advanced in experimental group compared with the control group, with the values of (13.70±6.22) vs. (14.56±5.18) min, (14.05±3.75) vs. (15.88±3.70) min, (16.90±5.25) vs. (18.00±4.49) min, but there was no statistical significance (P>0.05). Compared with the control group, after 24 weeks, the muscle oxygen at 1 minute in the second stage was significantly decreased (3.85%±0.58% vs. 2.43%±0.24%) and the heart rate at 2 minutes in the third stage was significantly increased [(3.33±0.58) vs. (5.06±0.57) times per min, P<0.05].

Portable and wearable devices combined with exercise management can decrease the blood glucose level, and improve muscle oxygen metabolism and cardiorespiratory endurance in T2DM patients.

To investigate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment on serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM).

Seven databases of PubMed, Embase, Cochrane Library, China Biomedical, CNKI, Wanfang, and VIP were accessed by computer for a time frame from January 2015 to April 2021. Randomized controlled trials (RCT) about SGLT2i in the treatment of T2DM patients were screened, the SUA levels of patients before and after SGLT2i treatment were extracted. Meta-analysis was performed using RevMan 5.3, and regression analysis was performed using Stata 14.0.

A total of 51 RCT involving 12 985 T2DM patients were included. Meta‐analysis showed that compared with the placebo control group, the total SGLT2i treatment group significantly reduced SUA levels in patients with T2DM [weighted mean difference (WMD)=-32.70 μmol/L, 95%CI -36.80—-28.60 μmol/L, I²=98%, P<0.01]. Subgroup analysis based on “drug and dose” showed that compared with the placebo, Canagliflozin group reduced SUA levels (WMD=-11.85 μmol/L, 95%CI -14.48—-9.23 μmol/L, I²=80%, P<0.01), Dapagliflozin group reduced SUA levels (WMD=-39.45 μmol/L, 95%CI -48.21—-30.69 μmol/L, I²=100%, P<0.01) and Empagliflozin group reduced SUA levels (WMD=-44.48 μmol/L, 95%CI -51.47—-37.49 μmol/L, I²=70%, P<0.01), respectively. Subgroup analysis based on “SGLT2i single treatment or combination treatment with other hypoglycemic drugs” showed that the SGLT2i single treatment group (WMD=-24.70 μmol/L, P<0.01) and the combination group (WMD=-40.54 μmol/L, P<0.01) both lowered SUA levels. The regression analysis showed that the combination group had lower SUA levels than the monotherapy group (P=0.047). The results of the “duration of treatment” subgroup showed a reduction in SUA values for<24 weeks of SGLT2i treatment (WMD=-28.92 μmol/L, P<0.01), 24—48 weeks (WMD=-32.11 μmol/L, P<0.01) and>48 weeks (WMD=-37.73 μmol/L, P<0.01). The regression analysis showed no correlation between duration of treatment and SUA reduction (P>0.05).

SGLT2i can significantly reduce the SUA levels of T2DM patients, and the effects of reducing SUA levels may be different among SGLT2i. The combination of SGLT2i with other hypoglycemic drugs and the duration of SGLT2i treatment would not influence lowering SUA levels.

To investigate the protective effect of miR-520c-3p on cell pyroptosis of proximal tubular epithelial cell (PTEC) in diabetic kidney disease (DKD) and its molecular mechanism.

Human kidney specimens from patients with DKD (DKD group, n=4) were obtained from the First Affiliated Hospital of Zhengzhou University from June 2019 to December 2020, and the kidney specimens from unaffected portions of the kidney tumor with normal glucose tolerance were served as normal controls (NC group, n=4). Renal histopathological changes were examined by hematoxylin and eosin (HE) staining, periodate-Schiff staining (PAS) and transmission electron microscope (TEM). PTEC (HK-2 cell line) were cultured with normal glucose (NG group, 5.6 mmol/L glucose) and high glucose (HG group, 30.0 mmol/L glucose), and transfected with miR-520c-3p mimics, miR-520c-3p inhibitor, miR-520c-3p negative control (NC) plasmid, thioredoxin-interacting protein (TXNIP) plasmid and TXNIP negative control (NC) plasmid. Cell pyroptosis was determined by dynamic real-time monitoring of living cells and propidium iodide (PI) staining. The expression of miR-520c-3p, TXNIP, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved caspase-1, Gasdermin D (GSDMD) were detected by immunofluorescence staining, fluorescence in situ hybridization (FISH), real time-PCR and Western blotting. The IL-1β concentration in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA) kit. Interaction between miR-520c-3p and TXNIP was analyzed by dual luciferase activity assay. Data were presented as the mean±standard deviation (SD), and the significance was determined using unpaired Student′s t-test for two groups and one-way analysis of variance (ANOVA) for multiple groups.

Compared with the NC group, inflammatory cells were increased in the DKD group, accompanied with reduction of miR-520c-3p expression level and increased of TXNIP level (P<0.05). The co-localization between renal tubule specific marker aquaporin (AQP1) and NLRP3 and that between AQP1 and GSDMD were both increased. In HK-2 cells, compared with NG group, cell pyroptosis was increased in HG group, accompanied with reduction of miR-520c-3p level and increases of TXNIP, NLRP3, cl-caspase-1 and GSDMD levels, as well as IL-1β concentration in cell supernatant (P<0.05). Compared with miR-520c-3p mimics NC plasmid,overexpression of miR-520c-3p inhibited cell pyroptosis, decreased the level of TXNIP mRNA, TXNIP, NLRP3, cleaved caspase-1, GSDMD and IL-1β protein levels induced by high glucose (P<0.01), and reduced the co-localization between TXNIP and NLRP3 (P<0.05). However, compared with miR-520c-3p inhibitor NC plasmid, inhibition of miR-520c-3p promoted cell pyroptosis and increased TXNIP mRNA level as well as TXNIP, NLRP3, cleaved caspase-1, GSDMD protein levels and IL-1β concentration (P<0.01). Additionally when compared with TXNIP NC plasmid, overexpression of TXNIP abolished the inhibitory effects on TXNIP, NLRP3, cleaved caspase-1 and GSDMD by miR-520c-3p mimics and increased the co-localization between TXNIP and NLRP3 (P<0.05). Dual luciferase reporter assay indicated that TXNIP was the direct target of miR-520c-3p. Meanwhile, miR-520c-3p inhibited cell pyroptosis induced by high glucose through regulating TXNIP expression.

miR-520c-3p alleviated PTEC pyroptosis induced by high glucose through inhibition of the TXNIP/NLRP3 pathway.

To investigate the protective effects and mechanisms of sacubitril/valsartan on ventricular myocytes in diabetic rats.

Forty Sprague Dawley (SD) rats aged 6 to 8 weeks were used to establish type 1 diabetic model by intraperitoneal injection of streptozotocin. Rats were divided into control group, diabetes (DM) group, diabetes+valsartan (DM+Val) group (30 mg·kg^-1·d^-1) and diabetes+sacubitril/valsartan (DM+Sac/Val) group (60 mg·kg^-1·d^-1). After 8 weeks, cardiac function indexes of rats in each group were measured by cardiac ultrasound: left ventricular ejection fractions (LVEF), left ventricular short axis shortening rate (LVFS). Hematoxylin-eosin (HE) staining was used to observe the structure and morphology of ventricular myocytes, and apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuria triphosphase-biotin nick end labeling (TUNEL) staining. Protein and mRNA expression of B-cell lymphoma-2 associated X (Bax), B-cell lymphoma-2 (Bcl-2), C/EBP homologous protein (CHOP) and glucose regulatory protein 78 (GRP 78) of ventricular myocytes were tested by Western blotting and polymerase chain reaction (PCR), respectively. Immunohistochemical staining was used to observe the expression of GRP 78. Independent-sample t test, one-way analysis of variance (ANOVA), Mann-Whitney U or Kruskal-Wallis H test were used for comparison between groups.

TUNEL staining showed that apoptosis rate of ventricular myocytes in DM group [(2.116±0.305) %] was increased compared with control group [(0.164±0.048) %]. Compared with DM group, apoptosis rate of ventricular myocytes was decreased in DM+Val group [(1.121±0.097) %] and DM+Sac/Val group [(0.513±0.031) %]. The apoptosis rate of ventricular myocytes in DM+Sac/Val group was lower than that in DM+Val group (all P<0.001). In comparison with control group, the protein and mRNA expression of pro-apoptotic protein Bax was increased in DM group, while the expression of anti-apoptotic protein Bcl-2 was decreased, and the Bcl-2/Bax ratio was significantly decreased. The protein and mRNA expression of Bax were decreased and the protein and mRNA expression of Bcl-2 were increased in DM+Sac/Val group compared with DM group (all P<0.05). In comparison with control group, the protein and mRNA expressions of endoplasmic reticulum stress-related proteins CHOP and GRP 78 in DM group were significantly increased. Compared with DM group, the protein expression of CHOP and the mRNA expression of CHOP and GRP 78 in DM+Val group were significantly decreased, the protein and mRNA expression of CHOP and GRP 78 in DM+Sac/Val group were significantly decreased (all P<0.05).

Sacubitril/valsartan reduces the apoptosis of ventricular myocytes and improves cardiac function in diabetic rats, which may be related to the inhibition of endoplasmic reticulum stress.

The clinical manifestations and genetic characteristics of a child with Donohue syndrome were reported, and the relevant literature was reviewed. The children have typical goblin-like appearance, developmental retardation, black acanthus, increased hair, abdominal swelling and other clinical manifestations. Laboratory tests showed fasting hypoglycemia, normal postprandial blood glucose, and significantly increased insulin and C-peptide in blood. Genetic testing found that the child carried insulin receptors (INSR) Compound heterozygous mutations: c.2810C>T, c.2907T>G, among which c.2907T>G has not been reported in the literature. Donohue syndrome is rareINSRHereditary insulin resistance syndrome caused by gene mutation, which currently has no effective treatment and poor prognosis. The diagnosis and treatment process of a child with Donohue syndrome is reported in order to improve clinicians' understanding of the disease.

Diabetes is an important public health problem in the world, and the occurrence and development of its complications affect the quality of life of patients. Therefore, the focus of diabetes treatment is not only to control blood sugar, but also to reduce the incidence and mortality of diabetic complications. In recent years, in the exploration of hypoglycemic drugs, sodium-glucose cotransporter 2 inhibitors combined with glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes have shown many benefits such as lowering glucose, lowering blood pressure, weight loss, lowering lipids, and improving cardiovascular, kidney and liver functions. The efficacy and safety of sodium-glucose co-transporter 2 inhibitors combined with glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes were summarized.

With the in-depth research on intestinal flora, the clinical therapeutic value of fecal bacteria transplantation (FMT) has been re-recognized by scholars. At present, FMT has been written into the clinical treatment guidelines of Clostridium difficile infection. In the exploration of FMT, the author found that it has good performance in the treatment of polymetabolic diseases such as diabetes, hypertension, obesity, fatty liver and hyperuricemia. This article now reviews the application of FMT in metabolic diseases.

Neuronin 4 (NRG4) is a novel adipokine that plays an important role in energy balance and glycolipid metabolism. In recent years, the relationship between NRG4 and type 2 diabetes mellitus (T2DM) and coronary heart disease has received more and more attention. NRG4 is expected to be a novel predictor of the risk of T2DM and coronary heart disease. This article reviews the relationship between NRG4 and T2DM and coronary heart disease.

Mesenchymal stem cells are a kind of stem cells derived from various tissues of human body, which have the potential to differentiate in multiple directions and secrete related growth promoting factors. Exosomes are one of the important active components secreted by mesenchymal stem cells. The wounds of diabetic patients heal poorly due to local microenvironment changes. Mesenchymal stem cells and exosomes can promote diabetic wound healing through various pathways. This paper reviews the research progress of mesenchymal stem cells and exosomes in promoting diabetic wound healing, the application pathways and limitations of mesenchymal stem cells and related exosomes.

As one of the chronic serious complications of diabetes, diabetic foot (DF) has a high amputation rate and mortality rate, which brings a heavy economic burden to patients and society. Delayed referral is an important reason for the high amputation rate and mortality rate of DF patients in China and even the world. Scholars from the International Diabetic foot Care Group and D-foot International Team have developed a set of rapid referral paths for DF and implemented them in Britain, France, Germany, Italy and Spain according to the legislation of various countries. However, China has not yet formulated a complete set of rapid referral paths. In addition, patients and some primary health care staff still have misunderstandings about DF, which leads to DF patients in some areas still cannot get timely and standard diagnosis and treatment. Therefore, it is more and more urgent to improve a complete set of rapid referral paths and realize the linkage mode of DF prevention and treatment between grass-roots and general hospitals.

Fragile diabetes is characterized by islet failure, great blood sugar fluctuation, severe hypoglycemia and hyperglycemic ketosis alternating, which is harmful, brings a heavy psychological burden to patients, and leads to a significant increase in the risk of long-term complications. It is a clinically refractory diabetes, which is common in patients with type 1 diabetes and long-course type 2 diabetes. All patients with fragile diabetes need insulin replacement therapy, and good blood sugar control during treatment requires many aspects of refined management. This article explains the management of refractory fragile diabetes from the refinement of blood glucose monitoring, insulin use, structured education, and the current new technology, in order to improve the blood glucose control of patients, thereby reducing the risk of acute and chronic complications and improving the quality of life of patients.