Volume 13 · Issue 07 · 2021

Diabetic neuropathy is the most common chronic complication of diabetes, but it is not paid enough attention at present, the screening rate, diagnosis rate and treatment rate are low, and the diagnosis and treatment need to be more standardized. Therefore, the Neurological Complications Group of the Diabetes Branch of the Chinese Medical Association formulated the Expert Consensus on the Diagnosis and Treatment of Diabetic Neuropathy (2021 Edition), which systematically elaborated the current epidemiology, etiology and pathogenesis, classification, screening methods, diagnostic criteria, treatment methods and prognosis of diabetic neuropathy. On the occasion of the release of this consensus, this paper focuses on reviewing the development course and current situation of prevention and control of diabetic neuropathy diagnosis and treatment, and puts forward the focus and improvement strategies of screening, diagnosis and treatment of diabetic neuropathy, so as to improve the prevention and treatment level of diabetic neuropathy in China.

Due to the aging of society and the continuous increase of diabetes prevalence, diabetes combined with cognitive dysfunction is also increasingly common. Endocrinology Branch of Chinese Medical Association organized domestic experts in related fields to write the "Expert Consensus on Diabetic Cognitive Dysfunction". Actively advocate the standardized management of diabetic cognitive dysfunction, and comprehensively give expert suggestions on the clinical diagnosis and treatment of diabetes with cognitive dysfunction in the consensus, which will surely help to improve clinicians' understanding and standardized management level of diabetes with cognitive dysfunction, improve patients' quality of life and improve patient outcomes.

Diabetes Self-Management Education (DSME) and Diabetes Self-Management Support (DSMS) play a key role in the diagnosis and treatment of diabetes. With the development of society, the progress of artificial intelligence, Internet and other technologies has provided many new models and new opportunities for diabetes education and management. This paper expounds the impact of software and hardware on the development of DSME/DSMS system from the aspects of mobile health technology, artificial intelligence, wearable devices and personal terminal devices, and social media, discusses potential opportunities and challenges, and explores the development trends of future diabetes education models.

Working night shifts can cause abnormal glucose metabolism. The study of the effects of different sleep supplementation styles on metabolism in rats simulating night shift work is the first study in the world to investigate the effects of different sleep supplementation styles on metabolism after night shift work. The results showed an increase in corticosterone concentration, an increase in food intake, a decrease in body weight gain, and impaired glucose tolerance and isletitis in rats working on night shifts. After early sleep supplementation, late sleep supplementation and intermittent sleep supplementation, compared with normal work and rest rats, it was found that intermittent sleep supplementation after night work had the least effect on metabolism.

Traditional wisdom has it that type 2 diabetes is a lifelong disease that cannot be cured once it is sick. However, with the continuous progress of medical technology, this concept has been challenged, and the dawn of reversing diabetes has begun to appear. Strategies to reverse type 2 diabetes include five aspects: prevention before it occurs, weight loss, intensive hypoglycemia, metabolic surgery, and pancreas or islet transplantation. The mechanism of reversal is mainly to restore the personal fat threshold, relieve glycolipid toxicity or improve intestinal hormones and intestinal flora, so that dedifferentiated insulin beta cells can regain the ability to secrete insulin. The odds of achieving type 2 diabetes reversal depend on age, sex, course of the disease, blood sugar, weight and many other factors. Taking the most effective measures for the right population is the key to successfully reversing type 2 diabetes.

The development of computer-assisted blood glucose management system (CDSSGM) mainly goes through two stages: intravenous insulin adjustment program and subcutaneous insulin adjustment program, which correspond to the stable glucose control demand of intensive care unit and the informatized blood glucose management demand of the whole hospital, respectively. The results suggest that CDSSGM can achieve higher proportion of target blood glucose, lower frequency of hypoglycemia, and more satisfactory medical and nursing use. The progress of information technology provides conditions for the external development of CDSSGM, and the standardization, safety and efficiency of medical behavior are the internal driving forces to promote its development. At present, there is commercialized insulin dose adjustment software to assist hospital blood glucose management, and the in-depth integration of medical big data and artificial intelligence will promote the upgrading of intelligent hospital blood glucose management level.

With the increasing incidence of diabetes in China, more and more attention has been paid to diabetes and its related complications. However, clinicians still lack knowledge of the related concepts, clinical diagnosis, treatment and prevention of diabetic cognitive dysfunction. The Endocrinology Branch of Chinese Medical Association specially organized experts to analyze the current situation of diabetic cognitive dysfunction at home and abroad, and combined with the research progress at home and abroad, the Expert Consensus on Cognitive Dysfunction of Diabetic Patients was formed, aiming at guiding and helping clinicians to standardize and comprehensively manage the cognitive dysfunction of diabetic patients and improve the clinical outcome of cognitive dysfunction of diabetic patients in China. The consensus covers the overview, definition and classification, epidemiology and pathogenesis, risk factors, screening, diagnosis and differential diagnosis, treatment and prevention of diabetic cognitive dysfunction.

Soluble Double Insulin Formulation Degusasp Double Insulin Formulation (IDegAsp) contains 70% insulin degusasp and 30% insulin aspart, the two components exist independently in the formulation and each exert its own effects after subcutaneous injection. In order to help the clinical application of IDegAsp more reasonably and standardizedly, experts have discussed and formed this edition of "Expert Guidance on Clinical Application of Deguspart Double Insulin" for many times, which explains the mechanism of action and pharmacokinetic characteristics of IDegAsp, and gives suggestions for clinical application. IDegAsp can be injected once daily or twice daily, taking into account both fasting blood glucose and postprandial blood glucose control. Clinical evidence supports the use of IDegAsp in a variety of clinical scenarios and can be used for initiation or intensive therapy with insulin. IDegAsp is recommended as one of the options for patients who have failed to initiate insulin therapy on oral medication or require intensive insulin therapy.

To develop and validate a model for postprandial blood glucose (PBG) estimation in Asian patients with type 2 diabetes mellitus (T2DM).

The estimation model for PBG was developed and validated based on glycated hemoglobin (HbA_1c) and finger-based fasting blood glucose (FBG). The training cohort was drawn from a phase 4, multinational, randomized, controlled, 26-week trial comparing the efficacy and safety of insulin lispro low-mixture and insulin lispro mid-mixture as an insulin starter in Asian T2DM patients. The glycemic data at baseline (before insulin initiation) and 26 weeks were used for developing the estimation model for PBG. The validation cohort was drawn from a multicenter, randomized, and pragmatic trial comparing the efficacy and safety of basal insulin analog and insulin analog mid-mixture as an insulin starter in Chinese T2DM patients with inadequate glycemic control (HbA_1c ≥7.5%) following oral antihyperglycemic medication (OAM) treatment. The glycemic data at baseline and 24 weeks were used for validating the estimation model. Based on the data distribution of the training cohort, a linear regression model including two variables was used to develop the estimation model. The β regression coefficient of each selected model predictor and α intercept were estimated using the datasets which consisted of FBG, PBG, and HbA_1c. FBG and HbA_1c were selected as independent variables for the estimation for PBG. The goodness of fit was assessed using the decisive factor R². For model validation, the PBG value was estimated using this model and compared with the real PBG. The mean of individual differences between estimated PBG and real PBG and the 95% confidence interval (CI) were calculated to evaluate the accuracy of the estimation model. Additionally, the root mean square error (RMSE) was calculated.

The clinical trials for the training and validation cohorts enrolled, respectively, 403 and 814 patients with T2DM. Based on data distribution through scatter plot, a linear regression model including two variables, HbA_1c and FBG, was used for developing PBG estimation model: PBG (Unit: mmol/L) = 1.5×HbA_1c (Unit: %)+0.5×FBG (Unit: mmol/L)-4.1 (R²=0.57). In the validation cohort, the estimated PBG was (13.8±3.7) mmol/L and the real PBG was (13.7±4.6) mmol/L with the individual differences between the estimated PBG and real PBG being (0.1±3.4) mmol/L, 95%CI being -0.1 to 0.3, and P being 0.525. The RMSE for the estimation model was 3.40 mmol/L.

Patients with T2DM treated with OAM or insulin could estimate their PBG with HbA_1c and FBG using this estimation model with reasonable accuracy.

To investigate the association between meteorin-like protein (Metrnl) and diabetic kidney disease (DKD) in the patients with type 2 diabetes mellitus (T2DM).

This was a cross-sectional study. From October 2018 to August 2019, the patients with T2DM who were admitted to the Department of Endocrinology in 900 Hospital of the Joint Logistics Team, Fuzong Clinical Medical College of Fujian Medical University were enrolled. According to the urine albumin creatinine ratio (UACR), the patients were divided into three groups: normoalbuminuria group (UACR<30 mg/g), microalbuminuria group (UACR: 30 to 300 mg/g), and macroalbuminuria group (UACR>300 mg/g). The related clinical data of serum Metrnl, serum monocyte chemotactic protein 1 (MCP-1), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA_1c), UACR, the lipid profile and the estimated glomerular filtration rate (eGFR) of the patients were evaluated. The differences of baseline data among different albuminuria groups were compared with analysis of variance (ANOVA) or Kruskal-Wallis test. Spearman correlation analysis was used to evaluate the correlation between Metrnl level and anthropometric and laboratory indexes. Based on serum Metrnl level, the binary logistic regression model was used to obtain the odds ratio (OR) of and 95% confidence interval (CI) of DKD risk. The diagnostic efficacy was evaluated by the receiver operating characteristic (ROC) curve.

A total of 98 patients with T2DM were included in the study, including 35 patients in the normoalbuminuria group, 31 patients in the microalbuminuria group, and 32 patients in the macroalbuminuria group. There were statistically significant differences in the levels of Metrnl and MCP-1 among the three groups (P<0.05). Compared with the normoalbuminuria group, the serum levels of Metrnl and MCP-1 were significantly increased in the microalbuminuria group and the macroalbuminuria group. Compared with the microalbuminuria group, the serum levels of Metrnl and MCP-1 were also significantly increased in the macroalbuminuria group. The differences were statistically significant (P<0.05). The level of serum Metrnl was positively correlated with age (r=0.226), urea nitrogen (r=0.358), creatinine (r=0.512), uric acid (r=0.295), UACR (r=0.628) and MCP-1 level (r=0.690) (all P<0.05), while the level of serum Metrnl was negatively correlated with eGFR (r=-0.551, P<0.01). After controlling for traditional risk factors such as age, sex, BMI, HbA_1c, and uric acid, the OR value for DKD was 11.907 (95%CI 3.321 to 42.695) in the highest tertile of Metrnl compared to the lowest. The ROC curve to diagnose DKD revealed an area under the curve (AUC) of 0.791 for Metrnl.

Serum Metrnl level was significantly increased in DKD patients with abnormal proteinuria, which was positively correlated with UACR and MCP-1, and negatively correlated with eGFR.

To observe the effect of zinc supplementation on the changes of myocardial adenine monophosphate activated protein kinase (AMPK), dynamin related protein 1 (Drp1) and oxidative stress in type 1 diabetic mice (T1DM), and to preliminarily explore the mechanism of the protective effect of zinc treatment on diabetic cardiomyopathy.

Sixty eight-week-old male FVB mice were selected, and a small dose (50 mg/kg) of streptozocin (STZ) was continuously injected intraperitoneally for five days to construct a T1DM myocardial injury mouse model. After successful modeling, the mice were divided into three groups by block randomization: control group (group A, n=20), diabetic myocardial injury group (group B, n=18) and diabetic myocardial injury model+high zinc diet group (group C, n=18). Groups A and B were given normal zinc diet (the content of zinc is 30 mg/kg) and group C was given a high-zinc diet (the content of zinc was 150 mg/kg) for 3 months. The body weight, serum glucose, malondialdehyde and superoxide dismutase levels were measured; the cardiac function, left ventricular ejection fraction (EF value), the ratio of the early peak and late filling rates of systolic and diastolic ventricles (E/A ratio) and left ventricular end diastolic diameter (LVDD) were also detected; the pathological changes of myocardial tissue were observed. Furthermore, the protein expressions of AMPK, phospho adenine monophosphate activated protein kinase (pAMPK^Thr172), Drp1 and phospho dynamin related protein1 (pDrp1^ser616) were measured by Western blotting, and the ratios of pAMPK^Thr172/AMPK and pDrp1^Ser616/Drp1 were calculated. One-way analysis of variance (ANOVA) was used for comparison among multiple groups.

The differences in weight, blood glucose, malondialdehyde and superoxide dismutase levels, E/A ratio, EF value and LVDD among the three groups A, B, and C were statistically significant (P<0.05). The levels of plasma malondialdehyde were higher and superoxide dismutase were lower in group B compared with those of group A, while the levels of malondialdehyde were lower and superoxide dismutase were higher in group C. Compared with group A, the E/A ratio and EF value of group B decreased, while group C increased compared with group B. Compared with group A, the pAMPK^Thr172/AMPK value of group B decreased, while group C was higher than group B. The pDrp1^Ser616/Drp1 value of group B increased compared with group A, while Group C was lower than group B. All the differences above were statistically significant (P<0.05). Zinc supplementation increased the phosphorylation level of AMPK^Thr172 and decreased the phosphorylation level of the Drp1^Ser616 in the myocardial tissue.

Zinc supplementation may be effective in inhibiting the oxidative stress of diabetic myocardial injury and myocardial cell mitochondrial division through regulating AMPK/Drp1 pathway.

To investigate the role of mouse hepatic mucosal-associated T (MAIT) cells in type 2 diabetes mellitus.

Five-week-old male C57BL/6 mice were randomly divided into normal control group (n=5) and model group (n=5). The model of type 2 diabetic mice was established via 16 weeks of high-fat-diet feeding. Hepatic lymphocytes were separated from liver samples using density gradient centrifugation. The frequency of hepatic MAIT cells and cytokine expressions of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-17 and IL-4 in hepatic MAIT cells were analyzed by flow cytometry. The gene expressions of key molecules involved in hepatic glucose metabolism [glucose-6-phosphatase (G6pc), pyruvate kinase M1/2 (PKm), 6-phosphofructokinase 1 (Pfk1)] were evaluated in primary hepatocytes co-cultured with hepatic MAIT cells sorted from diabetic mice. Independent-samplest test was used to compare between two groups.

Compared with the normal control group, the body weight [(49.87±0.99) vs. (26.41±0.81) g, respectively, t=36.76, P<0.05) and fasting blood glucose [(11.52±0.46) vs. (6.12±0.48) mmol/L, respectively,t=16.22, P<0.05] were increased significantly in the model group. The hepatic steatosis was obvious in the model group. Compared with the normal control group, the frequency of hepatic MAIT cells was increased significantly [(1.06±0.46) % vs. (0.42±0.20) %, respectively,t=2.85, P<0.05] and the expression of IFN-γ in hepatic MAIT cells was elevated significantly [(27.18±13.14) % vs. (47.56±13.08) %, respectively,t=2.46, P<0.05] in the model group. In vitro co-culture experiments showed that hepatic MAIT cells from diabetes predominantly upregulated mRNA levels of G6pc (t=14.60, P<0.01) and downregulated mRNA levels of Pkm (t=22.27, P<0.01) and Pfk1 (t=4.28, P<0.05) of primary hepatocytes.

Hepatic MAIT cells of diabetic mouse are elevated in frequency and IFN-γ expression, and contributed to the excessive hepatic output of glucose, which is highly correlated with type 2 diabetes mellitus.

To observe the effect of mitochondrial nicotinamide adenine dinucleotide phosphate dependent isocitrate dehydrogenase (IDH2) on glucose metabolism in mouse hepatocytes.

AML12 cells were respectively treated with high glucose (HG) and low glucose (LG) for 24, 48 and 72 hours. mRNA and protein expression of IDH2 were detected. Lentiviral vectors were used to construct IDH2-knockdown cells (KD-IDH2) and related control cell line (KD-Ctrl), as well as IDH2-overexpression cells (OE-IDH2) and related control cells (OE-Ctrl). Cells were respectively treated with normal, high or low concentration of glucose, with 3 replications in each group. To assess intracellular reactive oxygen species (ROS) generation and cell apoptosis, flow cytometry was adopted for detection. Real-time quantitative reverse transcription polymerase chain reaction was used to detect mRNA expression levels of gluconeogenesis, glucose uptake, glycolysis-related genes [hexokinase 1 (HK1), pyruvate kinase (PKLR)], and expressions of proteins in insulin and glucagon signaling pathway [phosphoinositide 3-kinase (PI3K), phospho-PI3K (p-PI3K), protein kinase B (AKT), phospho-AKT (p-AKT), protein kinase A (PKA), phospho-PKA (p-PKA)] were determined by Western blotting. After stimulation with insulin and glucagon, glucose output capacity of hepatocytes was detected under low glucose condition. Uptake of 2-NBDG was determined by a multifunctional microplate reader to evaluate capacity of glucose uptake in liver cells. Comparison between two groups was performed with Student′st test.

After 48 hours of high glucose treatment, expression of IDH2 in AML12 cells decreased significantly (P<0.01). In KD-IDH2 group, IDH2 mRNA expression was (35.67±10.60) % of its control (P<0.01), which in OE-IDH2 group was increased by (4.59±0.77) fold of the control (P<0.01). Under low glucose condition, reduced glucose output capacity (P<0.01), higher glucose uptake rate (1.23±0.06 unfold of KD-Ctrl,P<0.01), increased activation of proteins in AKT/PI3K signaling pathway and decreased activation of PKA (P<0.01) were significantly observed in KD-IDH2 cells, while OE-IDH2 cells had opposite performances. Treatment with high glucose upregulated the expressions of glycolytic pathway-related genes in KD-IDH2 cells, such as HK1 and PKLR (P<0.05). At the same time, elevated levels of intracellular ROS (P<0.05) and cell apoptosis rate (P<0.01) were also detected.

Regulation of liver IDH2 expression affected glucose metabolism in hepatocytes. Decreased expression of liver IDH2 enhanced sensitivity of hepatocytes to insulin and down-regulated gluconeogenesis in low glucose condition. Overexpression of IDH2 increased glucose production of hepatocytes by augmenting its response to glucagon and reducing its sensitivity to insulin.

A case of adolescent-onset adult diabetes mellitus (MODY) type 5 caused by deletion of hepatocyte nuclear factor 1 β (HNF1 β) gene was reported. The disease is characterized by early onset diabetes, negative insulin-related antibody test and abnormalities of kidney, pancreas and reproductive system. It is autosomal dominant single genotype diabetes. Clinicians should improve their understanding of this disease, identify, diagnose and treat it early, and guide them to optimize fertility.

Cognitive impairment is an important complication of central nervous system in diabetic patients, which seriously affects the quality of life of patients. The possible mechanisms mainly include oxidative stress, β-amyloid accumulation and hyperphosphorylation of Tau protein, brain microenvironment, lymphatic dysfunction of central nervous system, etc. At present, the mechanism has not been fully elucidated.

Blood pressure management for diabetic people is an important means to reduce the risk of cardiovascular diseases. It is particularly important to develop individualized blood pressure control targets and select individualized antihypertensive drugs according to the blood pressure and comorbidities of diabetic patients. Novel hypoglycemic drugs such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists can also help with blood pressure control, bringing new options for diabetic people with hypertension.

Diabetic gastroparesis (DGP) is one of the common gastrointestinal complications of diabetes mellitus. The pathogenesis of DGP has not been fully understood. Appropriate animal models of DGP can help to explore the rules of prevention, occurrence, development, diagnosis and treatment of DGP in basic research. The preparation and evaluation of DGP rat models were reviewed in order to provide reference for the preparation of DGP rat models in the future.