Volume 15 · Issue 02 · 2023

The National Guidelines for the Prevention and Treatment of Diabetes with TCM at the Primary Level (2022) is the first TCM guideline for diabetes at the Primary Level in China. The guideline formulation process strictly follows the formulation methods and steps of evidence-based clinical practice guidelines, attaches importance to the guidance of TCM theory, and absorbs the latest research evidence of TCM treatment of diabetes in recent years. Through a survey of 1 150 physicians and interviews with 31 physicians in China, we understand the current situation of primary medical care, so as to construct the clinical problems of the guideline, and strive for the practicality and operability of the guideline at the primary level. During the compilation of the guidelines, several rounds of expert meetings were held, and more than 80 experts from more than 50 hospitals across the country participated in the discussion. The guide gives full play to the advantages of TCM in "treating diseases before diseases", emphasizes early screening, early evaluation and early intervention, advocates TCM non-drug therapies such as acupuncture, auricular acupuncture, acupuncture point application, acupuncture point massage and acupuncture point embedding, and integrates tea replacement and traditional exercise practices into the prevention and treatment system, focusing on solving patients' common symptoms to improve patients' quality of life, emphasizing the comprehensive management mode, especially the "three divisions co-management" team diagnosis and treatment mode with the participation of endocrine diabetes specialists, TCM practitioners and health managers is recommended. In order to facilitate medical staff to deeply understand and better apply this guide, the background and methodological points of the guide are summarized, and the key contents of the guide are interpreted.

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are common and often cause and effect. Numerous epidemiological studies have shown that NAFLD significantly increases the risk of T2DM, and the mechanism is not well understood. The liver is an important regulatory organ of glucose and lipid metabolism in the body, and plays a key role in maintaining the homeostasis of blood sugar and lipid in the body. This paper systematically expounds the pattern and mechanism of occurrence and development of NAFLD, especially the relationship between abnormal liver glucose metabolism and hyperglycemia. The NAFLD liver promotes gluconeogenesis, increases liver glucose output and increases blood glucose by producing a large amount of 17-hydroxyprogesterone, increasing the expression of the deubiquitinating enzyme USP14 gene. The risk of diabetes can be effectively reduced by improving fatty liver, which is of great significance for the prevention and treatment of diabetes.

In order to improve the level and service capability of diabetes prevention and treatment of grass-roots TCM, and make TCM play a role in diabetes prevention and treatment at grass-roots level, the State Administration of Traditional Chinese Medicine entrusted the Expert Steering Committee of Diabetes Prevention and Treatment of Chinese Society of Traditional Chinese Medicine to organize and formulate the National Guidelines for the Management of Diabetes Prevention and Treatment of Grassroots TCM (2022). The guidelines follow the theory of traditional Chinese medicine and evidence-based medicine, and take the practicality and operability of grass-roots clinical practice as the starting point. Multidisciplinary experts such as clinical experts of traditional Chinese and western medicine, endocrinology experts, evidence-based methodology experts, epidemiology experts, pharmacy experts, kinesiology experts, nutrition experts, and representatives of grass-roots general practitioners are organized to formulate them based on the Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2020 Edition) and the National Guidelines for the Prevention and Treatment of Diabetes in China (2022). This guide highlights the advantages of traditional Chinese medicine in treating diseases before diseases, advocates non-drug therapy, integrates tea replacement and traditional exercise practices into the prevention and treatment system, improves the quality of life of patients by focusing on solving common symptoms of patients, emphasizes the comprehensive management mode, and recommends the "three divisions co-management" diagnosis and treatment mode with the participation of endocrine diabetes specialists, traditional Chinese medicine practitioners and health managers. The main contents of the guide include the scope of application, normative citations, terms and definitions, requirements for grass-roots TCM prevention and treatment management, screening evaluation and diagnosis, lifestyle prevention and care, TCM prevention of common risk factors, treatment of common symptoms of diabetes, prediabetes, diabetes, common complications of diabetes, etc.

Diabetic patients are at high risk of progression to severe and critical illness after SARS-CoV-2 infection, and SARS-CoV-2 infection can also cause blood sugar fluctuations, induce diabetic ketoacidosis and even threaten life. Patients with type 1 diabetes have large blood sugar fluctuations and are more prone to ketoacidosis; Blood glucose control and health management during SARS-CoV-2 infection need urgent attention to avoid acute complications, hospitalization and poor prognosis. Based on the clinical experience and evidence of the diagnosis and treatment of novel coronavirus infection at home and abroad, this guide explains the aspects of diet, exercise, insulin adjustment, blood glucose monitoring, identification and treatment of diabetic ketosis and ketoacidosis, and psychological support, aiming at improving the management level of type 1 diabetic people during the period of novel coronavirus infection and improving their quality of life.

Glucocorticoids are widely used in the treatment of severe and critical patients with novel coronavirus infection, and induced hyperglycemia is a very prominent clinical problem. It has the clinical characteristics of high incidence, rapid occurrence, significant blood glucose increase and afternoon hyperglycemia, which requires temporary additional and more active blood glucose management. Before receiving glucocorticoid therapy, attention should be paid to inquiring about medical history and glucose metabolism screening, and blood glucose monitoring should be carried out according to glucose metabolism status. It is recommended that non-diabetic patients monitor their blood glucose at 4 pm to detect hyperglycemia early, while diabetic patients monitor more blood glucose. The hypoglycemic strategy should be formulated according to the patient's condition and blood glucose profile, and those with mild blood glucose increase should be treated with reasonable oral hypoglycemic drugs or glucagon-like peptide-1 receptor agonists; Insulin therapy is recommended for those with significantly increased blood glucose (>16.7 mmol/L), previous insulin therapy or parenteral nutrition. This management consensus was developed to enhance blood glucose management and improve prognosis during glucocorticoid therapy in patients with SARS-CoV-2 infection.

To explore the efficacy and safety of biphasic insulin aspart 50 (Ruisulin^®50) in treatment of patients with type 2 diabetes mellitus (T2DM).

A multicenter, randomized, open-labeled, parallel-controlled and positive control and the phase Ⅲ of clinical trial included the 542 T2DM patients having poor glucose control after using oral hypoglycemic drugs from July 29, 2016 to September 12, 2019. All patients were assigned to Ruisulin^®50 group or NovoMix^®50 group for 24 weeks by a ratio of 2∶1 based on block randomization. The decreased value and qualification rates of glycated hemoglobin A_1c (HbA_1c), fasting plasma glucose (FPG), 2 h postprandial blood glucose (2hPG), the incidence of hypoglycemic and adverse events, and the positive rate of aspartic islet specific antibody were compared at the end of 24 weeks. The full analysis set (FAS) and per-protocol dataset (PPS) were used for the effectiveness index analysis, and the safety set (SS) was used for the security index analysis. Analyses of matched samples t-test, t-test, and chi-square test were used.

All of 542 cases were included in the trial (364 cases received Ruisulin^®50 therapy and 178 cases received NovoMix^®50 therapy). There were 532 cases in FAS (356 cases received Ruisulin^®50 therapy and 176 cases received NovoMix^®50 therapy), 485 cases in PPS (325 cases received Ruisulin^®50 therapy and 160 cases received NovoMix^®50 therapy), and 533 cases in SS (357 cases received Ruisulin^®50 therapy and 176 cases received NovoMix^®50 therapy). At the end of 24-week treatment period, HbA_1c in Ruisulin^®50 group and NovoMix^®50 group decreased by 1.56%±1.42% and 1.54%±1.27%, respectively. FPG decreased by (1.94±3.08) and (1.43±2.53) mmol/L, and 2hPG decreased by (4.66±5.40) and (4.21±5.36) mmol/L, respectively. The decrease of the above indexes within the group was statistically significant (P<0.001), and there was no statistically significant difference between the two groups (P>0.05). Moreover, the incidence of hypoglycemic events was 65.27% (233/357) and 68.18% (120/176), the incidence of adverse events was 79.55% (284/357) and 72.73% (128/176), and after 24 weeks treatment, anti-insulin aspart antibody was 55.03% (186/338) and 57.83% (96/166) in Ruisulin^®50 group and NovoMix^®50 group, respectively. There were no significant differences in above parameters between the two groups (P>0.05).

Ruisulin^®50 provides similar glycemic control and safety profiles to NovoMix^®50, indicating that Ruisulin^®50 is a suitable therapeutic option in clinical practice.

To construct a non-weight-bearing exercise program suitable for patients with diabetic foot ulcer (DFU) in China and to evaluate its feasibility.

Based on the heuristic framework, from September to October 2021, 109 DFU patients were recruited in Xiangya Hospital of Central South University as the research participants. A cross-sectional survey, qualitative interview, sinicization scheme and expert meeting methods were used to form a non-weight-bearing exercise program based on self-determination theory. From November to December of the same year, 15 patients with DFU were recruited to conduct a quasi-experimental study to evaluate its safety and feasibility. Glycated hemoglobin A_1c (HbA_1c), ankle brachial index (ABI), lower limb muscle strength and ulcer area were collected before and after non-weight-bearing exercise intervention. A paired sample t-test was used to compare the indicators before and after the intervention.

DFU patients had poor motor behavior, and their movement disorders included psychological, physical and environmental disorders. The non-weight-bearing exercise program focused on movement disorders of DFU patients was constructed through expert meetings. The courses on the topics of self, ability and environmental needs were set up, and exercise videos and manuals were provided. The results of the quasi-experimental study showed that 87% (13/15) of DFU patients completed the non-weight-bearing exercise program (exercise intervention at least twice a week). There were no adverse events such as cardiovascular events (angina attack, sudden death), metabolic disorders (hypoglycemia, hyperglycemia), or bone, joint and ligament injuries during the intervention period. Compared with those before the intervention, ABI and lower limb muscle strength were increased, HbA_1c and ulcer area were decreased in DFU patients after intervention (P<0.05).

The constructed non-weight-bearing exercise program is in line with the clinical situation and exercise psychology of Chinese DFU patients, and has good safety and feasibility.

To systematically evaluate whether sodium-glucose cotransporter receptor-2 inhibitors (SGLT2i) increase the risk of diabetic ketoacidosis (DKA) in adults with type 2 diabetes mellitus (T2DM).

Randomized controlled trials (RCT) of SGLT2i in patients with T2DM included in Pubmed, Embase and Cochrane Evidence Based Medicine databases were searched from the establishment of the databases to November 30, 2021. Data such as sample size, age of subjects, body mass index (BMI), occurrence of DKA, type and time of hypoglycemic drugs used were extracted. Revman 5.4 software was used for meta-analysis. The risk ratio (RR) value and 95%CI were used as effect variables for dichotomous variables.

A total of 36 RCT involving 69 760 T2DM patients were included, and 139 DKA events occurred, including 106 DKA events in the SGLT2i group and 33 DKA events in the control group. Compared with the control group, SGLT2i group had a higher risk of DKA (RR=2.70, 95%CI 1.83-3.98, P<0.001). Subgroup analysis showed that T2DM patients with age>60 years (RR=2.72, 95%CI 1.83-4.04, P<0.001), BMI≥31 kg/m² (RR=2.72, 95%CI 1.82-4.06, P<0.001) and medication duration >52 weeks (RR=2.72, 95%CI 1.83-4.04, P<0.001) who received SGLT2i had a higher risk of DKA compared with their respective control groups. In the subgroups of drug types, the risk of DKA was higher in canagliflozin (RR=4.81, 95%CI 1.69-13.63, P=0.003) and ertugliflozin (RR=4.09, 95%CI 1.10-15.19, P=0.04) than in the control group.

This study suggests that SGLT2i increase the risk of DKA in patients with T2DM. Moreover, the older the age, the higher the BMI, and the longer the duration of receiving SGLT2i, the higher the risk of developing DKA, and the risk of DKA is also related to the type of medication.

To investigate whether brown adipose-derived neuregulin 4 (NRG4) can alleviate diabetic nephropathy (DN) through inhibiting renal inflammatory response.

DN model in mice was induced by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After the model establishment, wild-type (WT) and NRG4 knockout (KO) mice were divided into WT-DN+green fluorescent protein group (D-WT-GFP), KO-DN+green fluorescent protein group (D-KO-GFP) and KO-DN+NRG4 group (D-KO-NRG4). Then, adeno-associated virus green fluorescent protein or adeno-associated virus NRG4 transcription was injected into the brown adipose tissue in the interscapular region of mice. WT mice feeding normal chow diet were used as control group (WT-CON) (6 mice in each group). After 8 weeks of the experiment, glycated hemoglobin A_1c (HbA_1c), triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), low-density lipoprotein cholesterol (LDL-C), the ratio of urinary microalbumin to urine creatinine (UACR), serum interleukin-1 β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected. The pathological glomerular changes and podocyte injury were observed by periodic acid Schiff staining and transmission electron microscopy. The expression of F4/80 in renal tissues was measured by immunohistochemistry. The mRNA of IL-1β, IL-6 and TNF-α in renal tissue were analyzed by real-time quantitative polymerase chain reaction. The expression level of NRG4 protein in multiple tissues of D-KO-GFP group and D-KO-NRG4 group was detected by Western blotting. One-way analysis of variance (ANOVA) was used for comparison between groups. Pearson correlation analysis was used to analyze the correlation of serum NRG4 and the expression of serum inflammatory factors, UACR and F4/80 in renal tissue.

Compared with D-WT-GFP group, UACR was significantly increased in D-KO-GFP group (P<0.01), glomerular volume and mesangial matrix hyperplasia increased and podocyte injury, serum levels of IL-1β, IL-6 and TNF-α were significantly increased, and mRNA expression of these inflammatory genes in renal tissue was also increased (all P<0.01), and the expression of F4/80 in renal tissue increased (P<0.01). In addition, compared with the D-WT-GFP group, in the D-KO-GFP group, the HbA_1c, TG, TC, FFA, LDL-C and body weight increased (all P<0.01). Compared with D-KO-GFP group, D-KO-NRG4 group significantly decreased UACR level (P<0.01) and the expression of renal inflammation index F4/80 was decreased (P<0.01), the HbA_1c, TG, TC, FFA, LDL-C and body weight reduced (all P<0.01). Pearson correlation analysis showed that serum NRG4 was negatively correlated with the expression of IL-1β, IL-6, TNF-α, UACR and F4/80 in renal tissue (r=-0.548, -0.637, -0.553, -0.503, -0.554, all P<0.05). Western blotting results showed that the expression level of NRG4 protein in brown fat of D-KO-NRG4 group was higher, but the expression level of NRG4 protein in liver, kidney, skeletal muscle and white fat was lower (all P<0.05).

Brown adipose-derived NRG4 can reduce renal inflammatory response, proteinuria and renal injury in DN mice.

To investigate whether sodium butyrate (NaB) ameliorates inflammation and fibrosis in diabetic kidney disease (DKD) through histone lysine butyrylation (Kbu).

Twenty-four eight-week-old C57BL/6 male mice(16-17 g) without specific pathogen free (SPF) were randomly divided into normal control group (NC group), high-fat diet combined with streptozotocin (50 mg/kg) intraperitoneal injection of DKD model group (DKD group), intraperitoneal injection of NaB solution (40 mg/kg every 48 hours) intervention group (DKD+NaB group) using the random number table method, with 8 mice in each group. Normal renal mesangial cells were cultured in vitro, moreover, they were divided into normal glucose (NG) group (5.56 mmol/L glucose), high glucose (HG) group (30 mmol/L glucose), HG+NaB group (30 mmol/L glucose, and 1 mmol/L NaB), HG+NaB+acetyltransferase active transcriptional coactivator (P300) inhibitors (A485) group (30 mmol/L glucose, 1 mmol/L NaB, and 10 μmol/L A485). The levels of serum inflammatory factors [monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6)], urinary albumin and urinary creatinine in each group of mice were detected by enzyme-linked immunosorbent assay (ELISA), and the urinary albumin-to-creatinine ratio (UACR) was calculated. The expression levels of IL-6, MCP-1 and transforming growth factor-β (TGF-β), PanKbu and H3K9bu proteins in mouse renal tissue and renal mesangial cells in each group were detected by Western blotting. Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression levels of TGF-β, fibronectin (Fn), and P300 in mouse renal tissue and renal mesangial cells in each group. HE and Masson staining were used to observe the degree of hardening and fibrosis of mouse renal tissue. One-way analysis of variance was used for comparison between groups.

Invivo experiments showed that compared with the DKD group, the levels of UACR, serum IL-6 and MCP-1 in the DKD+NaB group decreased, the expression of TGF-β, and Fn proteins and mRNA in renal tissues decreased, and the expressions of PanKbu, H3K9bu modification, and P300 protein and mRNA in renal tissues were significantly up-regulated (all P<0.05). HE and Masson stains showed that the degree of hardening and fibrosis of renal tissues improved. In vitro experiments showed that NaB upregulated PanKbu and H3K9bu modification levels in renal mesangial cells in a concentration-dependent manner. Compared with the HG group, the PanKbu and H3K9bu modification in the HG+NaB group were significantly increased, and the expression of IL-6 and TGF-β protein in renal mesangial cells was down-regulated. Compared with HG+NaB group, the PanKbu and H3K9bu modification in renal mesangial cells were down-regulated in HG+NaB+A485 group, and the expression of MCP-1, IL-6 protein, TGF-β protein, mRNA, and Fn mRNA was up-regulated (all P<0.05).

NaB may inhibit renal inflammation and fibrosis gene expression, and improve DKD kidney injury through Kbu pathway.

In the traditional diabetes management mode, the accuracy of in-hospital blood glucose monitoring and management data is poor, there are few personalized programs, non-endocrinological hyperglycemia is frequent, the consultation rate is low, and the whole hospital lacks professional and standardized blood glucose management; There are many patients outside the hospital and the awareness of self-blood sugar management is poor. Doctors are one-to-many, which makes management more difficult and difficult to achieve effective tracking management. Therefore, once chronic diseases such as diabetes are diagnosed, scientific and continuous standardized management is urgently needed. However, factors such as data fragmentation inside and outside the hospital and lack of doctor-patient interaction hinder doctors' management and service of patients throughout the disease course. The First People's Hospital of Yulin City, Guangxi actively thinks about coping with the current situation of clinical blood glucose monitoring and management. In the clinical practice of "the whole hospital blood glucose management center", the all-round intelligent blood glucose management system is the starting point of diabetes prevention and control, and the patient-centered blood glucose management is deeply integrated from the three dimensions of "smart medical care" for medical staff, "smart service" for patients and "smart management" for hospitals, so as to complete the full coverage of pre-, during-and post-diagnosis scenarios. Through the top-level design of blood glucose management integration in the whole hospital, department barriers are broken through, a multidisciplinary collaboration mode led by endocrinology department is established, and individualized plans, blood glucose control targets and follow-up plans are formulated for patients with abnormal blood glucose in the whole hospital, so that the blood glucose level of each inpatient can be controlled, so as to reduce the mortality and infection of related diseases caused by glucose metabolism disorders, shorten the preoperative waiting time and hospitalization time, save limited medical resources, and benefit the majority of patients.

Report a case of 27-year-old diagnosedLMNAFamilial local lipodystropia (FPLD) type 2 families due to heterozygous mutations in genes. The proband was admitted to hospital with the complaint of "finding that blood sugar was elevated for more than 6 years", and was diagnosed as FPLD type 2 based on clinical data and family history. Whole-exon high-throughput second-generation sequencing results from probands and their parents showed the presence ofLMNAGene c.1444C>T (p.R482W) heterozygous mutation. Probands were given intensive insulin therapy, supplemented by lipid-lowering therapy, blood sugar control was stable compared with before, and dyslipidemia was significantly improved compared with before. Combined with the literature, this paper discussesLMNAThe clinical characteristics, diagnosis and treatment points of FPLD patients caused by gene mutation are aimed at improving the clinical understanding of FPLD.

One combined case was reportedWFS1AndAPPL1Diagnosis and treatment of patients with adolescent-onset diabetes mellitus (MODY) with genetic mutations. The patient was a 13-year-old girl who was admitted to hospital because she "found that her blood sugar was elevated for more than 2 years". After admission, peripheral blood hereditary diabetes-related gene sequencing was performed, and it was detected that it carriedWFS1: c.992_994dup (p.lle332dup) andAPPL1: c. 1696-3C>G (p?) One heterozygous variant each, combined with the patient's clinical presentation and auxiliary examination, the patient was considered to be MODY. This article reviews the diagnosis and treatment process of patients in order to improve the clinical awareness of early diagnosis of MODY, and carry out appropriate management and genetic counseling.

As the final product of purine metabolism, uric acid in human body may play the two completely opposite roles of pro-oxidation and anti-oxidation in different ranges. Most previous studies mainly focused on the effect of pro-oxidant properties of hyperuricemia on metabolic diseases. Many studies have confirmed that hyperuricemia interacts with hypertension, diabetes, chronic kidney disease, coronary atherosclerosis and other diseases. However, some recent studies have shown that too high or too low uric acid may promote the occurrence and development of chronic diseases. Patients with type 2 diabetes mellitus are prone to abnormal uric acid metabolism, and some researchers have found that changes in uric acid levels are related to microvascular complications. The influence and possible mechanism of serum uric acid on diabetic microvascular complications were reviewed.

Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy. Recent studies have shown that complement system plays an important role in GDM. Complement is a building block of the immune system, and complement activation is essential for maintaining a healthy pregnancy. Abnormal complement activation can affect the occurrence and development of GDM in many ways, such as acting as an inflammatory factor to mediate inflammation of maternal systemic and placental tissues to promote insulin resistance, and forming membrane attack complexes to lead to host autoimmune damage. At the same time, the occurrence of GDM can also lead to complement abnormalities, further increasing the susceptibility to GDM and GDM-related complications. This paper reviews the mechanism and research progress of complement regulatory proteins involved in GDM.

Corneal confocal microscopy (CCM), as a new detection method, can detect corneal nerve changes in diabetic patients non-invasively, quickly and accurately. In recent years, more and more studies have found that corneal nerve changes in diabetic patients are closely related to the occurrence and development of chronic complications such as diabetic neuropathy, diabetic retinopathy, diabetic kidney disease, etc. Therefore, corneal nerve-related parameters detected by CCM technology are expected to become one of the markers for early identification and screening of chronic complications of diabetes. This article reviews the research progress of corneal nerve changes and chronic complications of diabetes mellitus.

Diabetic skin lesions are one of the most common but overlooked diabetic complications, which seriously affect the quality of life of patients and even lead to the development of diabetic foot. In recent years, it has been proposed that diabetic skin lesions can predict the progression of diabetic complications and the occurrence of diabetic foot to a certain extent, so it is of great significance for the early diagnosis and treatment of diabetic skin lesions. However, at present, the pathogenesis of diabetic skin lesions has not been fully elucidated, and the early prevention and treatment of diabetic skin lesions has not attracted clinical attention. Therefore, there are many cases of severe diabetic foot and final amputation due to skin lesions. Combined with the latest progress at home and abroad, this paper summarized the pathophysiological changes of skin lesions in diabetic patients from the aspects of skin structure, chronic inflammatory damage and skin microenvironment, explored the potential pathogenesis of diabetic skin dysfunction, expounded the influence of skin microecology on diabetic skin lesions, and provided theoretical basis for early diagnosis and treatment of diabetic skin lesions.

Diabetic foot ulcers often delay healing, form chronic wounds, and biofilm-related infections are difficult to effectively control, gradually leading to adverse outcomes such as amputation, which are the main causes of disability and death in diabetic patients. Traditional treatment methods such as antibacterial, debridement and negative pressure suction are deficient. The development of biomaterial science has provided new treatment ideas for diabetic foot ulcer. This paper reviews the mechanism of chronic wound formation, biofilm attachment and research progress of new dressings in diabetic foot ulcer.

Polycystic ovary syndrome (PCOS) increases the risk of multiple pregnancy complications, including gestational diabetes mellitus (GDM), but there is significant clinical heterogeneity. This article reviews the influence of PCOS on pregnancy, risk factors of GDM occurring in PCOS, the influence of PCOS combined with GDM and GDM alone or PCOS alone on pregnancy, and the prevention of GDM occurring in PCOS patients.