Volume 11 · Issue 10 · 2019

diabetic retinopathy (DR) is one of the main causes of blindness in adults, which seriously threatens the quality of life of diabetic patients. How to prevent and treat early to reduce the risk of blindness in DR is the focus of academic attention at present. In recent years, the research of DR related mechanisms, the update of examination methods and the exploration of therapeutic drugs have provided a broad prospect for its early prevention and treatment. This paper focuses on the precise network formed by neurovascular coupling, and integrates neurovascular units to understand diabetic retinopathy from multiple angles. This paper summarizes the feasibility scheme of predicting and treating microvascular disease from three aspects: mechanism, examination and treatment, so as to provide a direction for the whole process and multi-level optimization management of DR.

Diabetic kidney disease is one of the common chronic microvascular complications of diabetes mellitus, which is the main cause of end-stage kidney disease. On the basis of traditional drugs, in recent years, more and more drugs such as sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists have shown beneficial outcomes for the kidney in large-scale clinical studies, bringing new directions to the treatment of diabetic kidney disease. This article reviews the progress of treatment strategies for diabetic kidney disease.

Kidney transplantation is one of the effective methods for the treatment of end-stage renal failure at present. However, many serious complications are prone to occur after kidney transplantation, among which post-transplant diabetes mellitus (PTDM) is one of the most important complications. Although the incidence of PTDM after renal transplantation varies from region to region, early identification/diagnosis, prevention, and treatment of PTDM are essential to improve survival after transplantation. For patients diagnosed with PTDM after renal transplantation, appropriate drugs should be selected for intervention in order to improve the quality of life of patients.

To investigate the effect of subclinical hypothyroidism (SCH) on the progression of early diabetic kidney disease (DKD) in type 2 diabetic patients.

A retrospective study was performed in 260 patients with early type 2 diabetic kidney disease [estimated glomerular filtration rate (eGFR) greater than 60 ml·min^-1· (1.73 m²) ^-1], who were repeatedly hospitalized in Tianjin Medical University Metabolic Diseases Hospital for more than 3 times from January 2008 to August 2018, including 198 patients with normal thyroid function and 62 patients with subclinical hypothyroidism. The first hospitalization was defined as the starting point, the last hospitalization was defined as the study endpoint. According to the levels of thyroid-stimulating hormone (TSH), free triiodothyronine and free thyroxine, the patients were divided into two groups: type 2 diabetes with normal thyroid function group (DM+EUT) and type 2 diabetes with subclinical hypothyroidism group (DM+SCH). The clinical data and renal function indicators of each hospitalization were collected. The average annual decreasing rate of eGFR (eGFR/Y), the average annual increasing rate of 24-hour total urine protein (24 h-TP/Y) and 24-hour urine microprotein (24 h-UMA/Y) were compared between these two groups. The influence factors of eGFR/Y were analyzed by Pearson or Spearman correlation and multiple linear regression.

There were no significant differences in baseline blood urea nitrogen, serum creatinine, uric acid between these two groups (t=-0.692, -1.432, -0.987, respectively, P>0.05). There were no statistical differences in the 24 h-TP and 24 h-UMA between these two groups (Z=-1.536, -1.412, P>0.05). The baseline eGFR in the DM+SCH group was lower than that in the DM+EUT group [(96.5±41.9) vs (99.4±42.2) ml·min^-1· (1.73 m²) ^-1, t=1.695, P=0.095], but the difference had no statistical significant. The eGFR/Y in the DM+SCH group was significantly higher than that in the DM+EUT group [6.02 (2.31, 8.92) vs 4.32 (1.35, 6.01) ml·min^-1· (1.73 m²) ^-1, Z=-2.241, P=0.02]. There was no significant difference in 24 h-TP/Y and 24 h-UMA/Y between these two groups (P>0.05). After adjustment for potential confounding factors (24 h-TP, systolic blood pressure and baseline eGFR) by multiple linear regression analysis, TSH remained to be associated with eGFR/Y significantly (t=2.149, P=0.036).

TSH is an independent risk factor for the average annual decreasing rate of eGFR. SCH can accelerate the progression of early DKD in type 2 diabetic patients.

To evaluate the diagnostic and therapeutic statusfor diabetic foot in hospitalized patients in Beijing, and investigate factors of severity and prognosis of diabetic foot (DF).

The clinical date of 1 646 hospitalized patients with DF from 9 hospitals in Beijing from 2010 Jan 1^st to 2014 Dec 31^st were retrospective surveyed. 907 of them were enrolled after standardization exam. Statistical analysis was performed for both performing rates and results of foot examination, vascular test and laboratory examination, and also for the influence factors for Wagner gradation. F test or non-parametric Mann-Whitney U test was performed for data analyzing, and chi-square analysis for percentages comparison.

Among 907 patients with DF, 610 were male, and 297 were female. The mean age was (66.24±11.87) year-old, and 91.0% (421/907) of them were above 50 year-old. The mean duration of diabetes was (13.45±7.71) years, and 71.4%(648/907) of them were over 7 years. Mean HbA_1c was (8.70±3.04)%. 46.4%(421/907) of them were diagnosed as peripheral artery disease (PAD), 60.6% (550/907) were diabetic peripheral neuropathy (DPN), 21.6%(196/907) were foot deformity, and 41.2% (374/907) of them had history of DF. 21.5%(195/907)of them had received amputation, and the mortality rate was 1.9%(17/907). Duration of hospital stay was 22.0 (14.0, 30.0) days, and hospitalization expense was 20 904.60 (11 883.53, 37 854.64) RMB. Association analysis showed that Wagner gradation was positively associated with PAD, hospitalization expense and amputation (r=0.191-0.444, all P<0.05), and negatively associated with DPN, hemoglobin (Hb), uric acid (UA), total cholesterol (TC), low density lipoprotein cholesterin (LDL-C) and history of DF (r=-0.169--0.122, P<0.05). Mortality rate increased along with Wagner 1 to 5 grades (Trend-χ²=5.051, P_trend=0.024) but was not significantly associated (P=0.054). Comparing with non-mortality subgroup, subgroup of mortality had a higher mean age and C-reactive protein (CRP), and a lower Hb and albumin (all P<0.05). Performing rate of foot deformity, PAD and DPN physical examination was 64.2% (582/907), 88.2% (800/907) and 43.3% (393/907), and the performing rate of ABI, HbA_1c and WBC was 33.2% (301/907), 58.1% (527/907) and 93.9% (852/907), respectively.

PAD and poor nutrition status is associated with Wagner grade. Arterial stenosis and DPN could reduce the recovering rate of Wagner grade. Advanced age, severe infection and malnutrition are risk factors of mortality in diabetic foot. Current status of diagnosis and treatment in DF has its defect in some aspects. It is critical to establish the standardized diagnosis and treatment process for DF.

To investigate the effect of microRNA-20a (miR-20a) on glucose metabolism in H9C2 cardiomyocytes, and reveal the mechanism of miR-20a on regulating insulin resistance and metabolic diseases.

The H9C2 cardiomyocytes was taken as the research object to establish the cell model of insulin resistance. The differential expression level of microRNAs was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The miRanda was applied to screen complementary binding sites between microRNA and Glut4 3′UTR. The H9C2 cells were transfected with miR-20a mimic and negative control (NC), the insulin resistant cells were transfected with miR-20a inhibitor and relative NC, respectively. To apply qRT-PCR for detecting expression levels of miR-20a and Glut4 mRNA. Western blotting was used to detect expression level of Glut4 protein in each group. Glucose consumption and uptake assay were used to measure glucose metabolism level in each group. Data were analyzed with one-way analysis of variance test or t test.

Compared with control group, the expression of miR-20a was significantly increased in insulin resistance group (3.14±0.12 vs 1.00±0.00, t= 17.79, P<0.01), the Glut4 mRNA and protein levels were obviously decreased in insulin resistance group (0.58±0.09 vs 1.00±0.00, t=4.71, P<0.05; 0.29±0.04 vs 1.00±0.00, t=17.18, P<0.01). There were complementary binding sites between miR-20a and Glut4 3′UTR. Compared with control group, the Glut4 mRNA and protein levels were decreased in miR-20a mimic group (0.36±0.11 vs 1.00±0.00, t=5.79, P<0.05; 0.25±0.05 vs 1.00±0.00, t=13.87, P<0.01). Glucose consumption and uptake levels were lower than those of control group respectively (48.74±3.95 vs 100.00±0.00, t=12.97, P<0.01; 211.30±13.30 vs 350.30±24.55, t=9.77, P<0.05). The Glut4 mRNA and protein levels were obviously increased in miR-20a inhibitor group compared with insulin resistance group (3.63±0.31 vs 1.00±0.00, t=8.39, P<0.01; 3.28±0.41 vs 1.00±0.00, t=5.55, P<0.05). Glucose consumption and uptake levels were increased than those of insulin resistance group respectively (240.30±34.12 vs 100.00±0.00, t=3.77, P<0.05; 267.70±31.86 vs 122.10±12.94, t=4.33, P<0.05).

MicroRNA-20a may affect glucose metabolism level of normal and insulin resistant H9C2 cardiomyocytes by regulating Glut4 expression.

To explore the effect of glucagon-like peptide 1 (GLP-1) on autophagy mediated by AMP activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) pathway in type 2 diabetic rats combined with Alzheimer′s disease (AD).

Total 80 SD rats were prepared as type 2 diabetes mellitus (T2DM) combined with AD models and 20 SD rats were as controls. Models were divided into model group, GLP-1 group (Liraglutide), GLP-1+AMPK inhibitor group (Compound C) and GLP-1+mTOR agonist group (L-leucine). After 1 week, bilateral hippocampus were extracted and Tau protein was detected by immunohistochemistry, p-AMPK/AMPK, p-mTOR/mTOR, LC3Ⅱ/LC3Ⅰ and beclin-1 were detected by western blotting.

Levels of Thep-mTOR/mTOR expression in the control group, model group, GLP-1 group, GLP-1+AMPK inhibitor group, GLP-1+mTOR agonist group were 0.19±0.03, 0.37±0.04, 0.23±0.02, 0.39±0.04 and 0.38±0.04, respectively; For Thep-mTOR/mTOR expression, levels in the model group were higher than those in the control group, levels in the GLP-1 group were lower than those in the model group, and levels in the GLP-1+AMPK inhibitor group and GLP-1+mTOR agonist group were higher than those in the GLP-1 group. The differences were significant between groups (t=2.739-2.936, P<0.05). Levels of p-AMPK/AMPK expression in the control group, model group, GLP-1 group, GLP-1+AMPK inhibitor group, GLP-1+mTOR agonist group were 0.89±0.10, 0.25±0.04, 0.90±0.11, 0.60±0.06 and 0.64±0.05 respectively; Levels of LC3Ⅱ/LC3Ⅰ expression were 2.29±0.30, 0.44±0.06, 1.85±0.20, 1.45±0.15 and 1.44±0.14 respectively; Levels of beclin-1 expression were 0.60±0.08, 0.28±0.03, 0.43±0.04, 0.34±0.04 and 0.33±0.02 respectively; For p-AMPK/AMPK, LC3Ⅱ/LC3Ⅰ, beclin-1 expression, levels in the model group were lower than those in the control group, levels in the GLP-1 group were higher than those in the model group, and levels in the GLP-1+AMPK inhibitor group and GLP-1+mTOR agonist group were lower than those in the GLP-1 group. The differences were significant between groups (t=3.062-11.980, all P<0.05).

GLP-1 could activate the autophagy response in T2DM combined with AD rats via AMPK-mTOR signaling pathway.

To investigate the effect of glucagon-like peptide (GLP)-1 receptor agonist (exendin-4) on the structure and function of pancreatic α cells in impaired glucose tolerance (IGT) rats.

A total of 54 male Wistar rats aged 4-5 weeks (150-170 g) were randomly divided into normal glucose tolerance (NGT) group (n=18) and IGT group (n=36). Rats in NGT group were administrated with routine diet and rats in IGT group were administrated with high-sugar, high-fat diet. 32 rats which were successfully established IGT models (the modeling success rate was 88%) were randomly divided into the IGT group (IGT group, n=16) and the Exendin-4 intervention group (Ex group, n=16). Levels of plasma glucagon, the percentage of α cells area and the glucagon protein expression in half rats of each group were detected by radioimmunoassay, immunohistochemical staining and immunofluorescence respectively. The ultrastructure of α cells were observed under transmission electron microscope. Rats in Ex group received Exendin-4 5 μg/kg subcutaneously, twice daily, while rats in the NGT and IGT group both received saline 5 μg/kg instead. Indicators were detected and collected after intervention for 4 weeks. One-way analysis of variance and least-significant difference was used for multigroup comparison.

(1) Before intervention, the plasma levels of glucagon, the area percentage of α cells, the glucagon protein expression and the secretory granules level of α cells in IGT group and Ex group were higher than those in the NGT group respectively [glucagon: (118.89±3.53), (116.12±3.37) vs (88.18±6.94) pg/ml; the area percentage of α cells: (26.91±7.77)%, (24.00±9.88)% vs (11.01±6.33)%; the glucagon protein expression: (307.44±71.85), (321.71±105.65) vs (71.74±12.10); the secretory granules level of α cells: (135.32±16.31), (129.64±12.78) vs (74.60±6.55); all P<0.05]. After intervention, the plasma levels of glucagon, the area percentage of α cells, the glucagon protein expression and the secretory granules levels of rat islet α cells were less in Ex group than those in the IGT group and the pre-intervention Ex group [glucagon: (86.89±6.23) vs (116.12±3.37), (118.39±4.36) pg/ml ( t=11.67, 11.72, all P<0.05); the area percentage of α cells: (15.09±3.35)% vs (24.00±9.88)%, (29.21±5.66)%; the glucagon protein expression: (102.10±26.28) vs (321.71±105.65), (327.55±155.53); the secretory granules level of α cells: (75.79±8.23) vs (129.64±12.78), (133.39±4.36) ( t=10.02, 17.49, all P<0.05]. There were no significant differences of above indicators between the NGT group and the post-intervention Ex group (all P>0.05); (2) Compared with the NGT group, the ultrastructural changes under electron microscopy in the IGT group showed: the nuclear membrane of α cells shrank and the nuclear chromatin was condensed; the mitochondria and endoplasmic reticulum were irregularly arranged, the mitochondria were swollen and deformed, and the cristae became shorter and shallower; the granula of endoplasmic reticulum fell off, the secretory granules increase, and the gap between dense core and boundary membrane narrowed or even disappeared. After intervention, compared with the IGT group before and during the intervention, the ultrastructural changes under electron microscopy in Ex group showed: the shrinkage of nuclear membrane and chromatin decreased, the abnormal proliferation and edema of mitochondria improved, the degranulation of rough endoplasmic reticulum was alleviated, the number of secretory particles decreased, and the gap between dense core and boundary membrane returned to near normal.

The number, ultrastructure and function of α cells have changed in the IGT stage. Exendin-4 can improve the number, ultrastructure and dysfunction of α cells in IGT rats.

With the deepening of electronic information technology and medical research, blood glucose monitoring technology has made rapid development. How to master as much valuable information as possible and efficiently transform and apply it to clinical practice has become a problem that we are constantly thinking about, and it is also one of the ways to achieve remarkable results in diabetic blood glucose management. Continuous glucose monitoring can obtain more blood glucose information, which is helpful for more precise, scientific and individualized blood glucose management. In order to better serve the blood glucose management of diabetic patients, this paper reviews the development of blood glucose monitoring technology, continuous glucose monitoring technology and its accuracy evaluation, and visual system analysis report in recent years.

Positive psychology is a new research trend that studies the positive aspects of human power and virtue. From the perspective of positive psychology, this paper introduces the concept of positive psychology and the positive psychological traits of diabetic patients such as subjective well-being, self-efficacy, psychological elasticity, post-traumatic growth and benefit discovery and their influencing factors, and reviews the application of positive psychological interventions such as happiness therapy, mindfulness intervention, psychological elasticity intervention and acceptance and commitment therapy in improving the psychological health of diabetic patients, so as to provide reference for the treatment and intervention of diabetic patients.

Diabetes mellitus is a metabolic disease characterized by increased blood sugar caused by multiple causes. The main harm lies in its chronic complications, which seriously affect health and quality of life. Epidemiological data suggest that diabetes-related chronic complications are an important cause of death in patients with type 2 diabetes mellitus (T2DM). Phospholipase A2 is an enzyme that catalyzes the hydrolysis of glycerophospholipids to produce a series of lipid mediators, thus participating in a variety of inflammatory responses. Previous studies have shown that phospholipase A2 is an independent predictor of coronary atherosclerotic heart disease. Recent studies have shown that phospholipase A2 as an inflammatory marker plays an important role in the development and development of chronic complications of T2DM, and it has a higher correlation with chronic complications of T2DM than traditional inflammatory markers such as C-reactive protein^[1]。 In this paper, the research progress and related mechanisms of phospholipase A2 in microvascular and macrovascular diseases are reviewed.

The prevalence of diabetes in China is high. With the rapid increase of the number of diabetic patients, the medical burden of hospitals increases, and the current situation of blood glucose management in and out of hospital is not satisfactory. In recent years, under the rapid development of Internet technology, informatization has been applied to the information management mode of blood glucose inside and outside the hospital, which has effectively improved the efficiency of medical work and promoted the effective integration and utilization of medical resources. At the same time, the rapid development of informatization in medical institutions is the basis for practicing graded diagnosis and treatment of diabetes, and dividing acute and slow treatment; For the majority of patients, it is necessary to adjust the treatment plan in time and improve the enthusiasm of patients to participate in self-management. The application of informatization in blood glucose management has effectively promoted the improvement of blood glucose management in the new era to a certain extent, and has a good application prospect.

The recently released CARMELINA study, following a median follow-up of 2.2 years in 6 979 patients with type 2 diabetes mellitus (T2DM) at high risk of cardiovascular disease and/or high risk of renal disease, showed that linagliptin had a long-term cardiovascular safety profile similar to placebo [incidence of cardiovascular composite event endpoints (linagliptin vs. placebo) 12.4% vs. 12.1%; hazard ratio (HR）=1.02； 95% CI (CI): 0.89~1.17, non-inferiority testP =0.000 2] and renal safety [renal composite event endpoint incidence (linagliptin vs placebo) 9.4% vs 8.8%;HR =1.04； 95% CI：0.89~1.22，P =0.62]； and confirmed that linagliptin treatment did not increase the risk of hospitalization for heart failure in patients (HR =0.90； 95% CI：0.74~1.08，P =0.26）。 In addition, linagliptin significantly delayed the progression of albuminuria compared with placebo (HR =0.86；P =0.003）。 The release of this study fills the data gap of dipeptidyl peptidase IV inhibitor (DPP-4i) in clinically common cardiovascular outcome studies in patients with T2DM with various degrees of renal impairment, and once again breaks the industry's concerns about the "class effect" of DPP-4i drugs increasing the risk of hospitalization due to heart failure.

Hexokinase (HK) is a key enzyme involved in glucose metabolism in the body, which can phosphorylate glucose to produce glucose-6-phosphate. There are four HK subtypes in human tissues, including HK-Ⅰ ~ Ⅳ. HK-IV, also known as glucokinase, is mainly distributed in the liver and pancreas. It is a monomeric isomerase. Because of its unique molecular structure and enzyme kinetics, it has become the only protease in the HK family that can be used as a glucose sensor. Its activity is directly regulated by glucose concentration, which starts the timely secretion of insulin and glucagon, sets the threshold of blood glucose homeostasis, regulates liver glycogen synthesis at the same time, and plays a central role in maintaining blood glucose homeostasis.