Volume 11 · Issue 01 · 2019

2019 marks the 10th anniversary of the founding of the Chinese Journal of Diabetes. The continuous progress of Chinese Journal of Diabetes is the common achievement of successive editors, editorial boards, contributing scholars, reviewers and editorial departments. This article will review the main progress made in the field of diabetes in China over the past 10 years, and will be summarized in nine parts. The first part of this publication is an epidemiological investigation, the second part is the progress related to diabetes diagnosis, and the third part is the clinical transformation of theory combined with practice. Among them, the epidemiological work has basically found out the family background and clarified the current situation. It is necessary for all walks of life to work together to further find the key leverage points, combine theory with practice, science with national conditions, and jointly explore the way of diabetes prevention and treatment in China.

With the increasing obesity in children and the strengthening of people's ability to recognize diabetes symptoms, the incidence of type 2 diabetes mellitus (T2DM) in children has gradually increased in many countries, including China. The treatment of T2DM is an individualized treatment based on healthy lifestyle. Individual differences and variations are large, especially in dietary treatment. It is difficult to summarize the experience, which limits the research advancement of T2DM in children. Therefore, it is necessary to implement strict randomized controlled trials, put forward a unified treatment plan, continuously promote and improve, and establish a guideline for the diagnosis and treatment of T2DM suitable for China.

In recent years, the prevalence of type 2 diabetes in China has increased rapidly, which has become a serious public health problem in China. Many factors may jointly contribute to the occurrence of diabetes epidemic in China, such as obesity, aging, dietary pattern, sedentary, genetic factors, epigenetic modification and other factors. In the past, we always focused on the prevention of diabetes on lifestyle interventions for high-risk groups, but lifestyle changes alone are not enough to change the increasing trend of type 2 diabetes prevalence. This article will analyze the causes of diabetes epidemic in China from three aspects: intrauterine environment, overweight/obesity and low physical activity level, and discuss the prevention strategies of diabetes in China.

Diabetic kidney disease (DKD) refers to chronic kidney disease (CKD) caused by diabetes and is usually a clinical diagnosis based on elevated urinary albumin and/or decreased estimated glomerular filtration rate, while excluding other CKDs. DKD is a common chronic complication of diabetes mellitus and an important cause of end-stage renal disease. The Microvascular Complications Group of Diabetes Branch of Chinese Medical Association has developed this guideline to standardize the diagnosis and treatment of DKD in China. This guideline has the following features: (1) highlighting clinical practicality; (2) Chinese evidence fully incorporated into the DKD field; (3) Pay attention to early screening; (4) Emphasize the importance of standardized and comprehensive management; (5) Pay attention to the role of new antihyperglycemic drugs in the treatment of DKD.

The effect of hypoglycemic therapy on cardiovascular prognosis has been widely concerned. Studies have shown that the intervention of multiple risk factors in the treatment of diabetes is indispensable, and the better the intervention effect, the better the cardiovascular outcome of patients. Glycosylated hemoglobin is a well-established predictor of myocardial infarction and stroke events, so setting near-normal blood glucose targets in diabetes treatment may bring cardiovascular benefits. Sulfonylureas are among the oral hypoglycemic drugs with the strongest hypoglycemic effect. The effect of such drugs on cardiovascular outcomes may be related to the way they are used, and attention should be paid to highly individualized treatment during clinical use.

To compare the risks of gastrointestinal side effects in patients with type 2 diabetes mellitus (T2DM) by Meta-analysis between metformin extended-release (MXR) and metformin immediate-release (MIR) treatment.

Databases of PubMed, the Cochrane Library, Web of Science, SinoMed, Wanfang and CNKI were searched for randomized controlled trials (RCTs) with therapy of MXR and MIR in T2DM patients from establishment of the database to March 2018. Stata 12.0 and RevMan 5.3 were used to analyze the risk of gastrointestinal adverse reactions.

Thirteen RCTs with a total of 3 039 patients were recruited. Compared with MIR treatment, MXR treatment significantly reduced the risks of nausea/vomiting, dyspepsia and flatulence (RR=0.61, 95%CI: 0.43-0.85, Z=2.87, P=0.004; RR=0.47, 95%CI: 0.30-0.74, Z=3.32, P=0.0009; RR=0.35, 95%CI: 0.17-0.69, Z=3.02, P=0.002) . The risks of diarrhea events were associated with the age of the patients: subgroup analysis showed that MXR treatment significantly reduced the risk of diarrhea in patients under 50 years of age (RR=0.21, 95%CI: 0.08-0.54, Z=3.25, P=0.001) instead of those patients over 50 years old (RR=0.99, 95%CI: 0.76-1.29, Z=0.08, P=0.940) ; Meta-regression showed that age was the main source of heterogeneity in diarrhea-studying group, while gender, body mass index, duration of diabetes, and drug dosage didn′t significantly affect the incidence of diarrhea events.

Compared with MIR treatment, MXR treatment could effectively lower the risks of nausea/vomiting, dyspepsia and flatulence in T2DM patients. MXR can be used as an alternative therapy for T2DM patients under 50 yrs who are unable to tolerate MIR treatment due to gastrointestinal side effects.

To evaluate the intervention effects of diet, exercise and health education on pre-diabetes in China by network meta-analysis.

A systematic search of CNKI, Wan-Fang, VIP, PubMed, Springer Link, Proquest, Highwire press, Uptodate, Cochrane database was carried out. Randomized control trials examining the influence of non-drug intervention on pre-diabetes in China were included. The data of prevalence rate, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) were analyzed by ADDIS 1.16.6. The count data were used the odds ratio (OR) and its 95% CI, and the measurement data were used the standardized mean difference (SMD) and its 95%CI as the efficacy analysis statistics. The results of each intervention were evaluated visually using rank probability.

A total of 14 studies were included. The potential scale reduced factor of all the three outcomes was close to 1 in the presence of good convergence and consistence (P>0.05). Dietary intervention was better than health education and exercise intervention in prevalence rate[OR(95%CI): 1.44(0.20, 11.69) and 1.94(0.42,8.82), respectively]. Dietary intervention was better than health education and exercise intervention in FPG[SMD(95% CI): 0.07(-0.43, 0.52) and 0.32(-0.38, 0.94), respectively]. Health education was better than dietary intervention and exercise intervention in PPG[SMD(95% CI): 0.62(-0.91, 2.19) and 0.81(-1.70, 3.44), respectively]. The rank probability showed that dietary intervention was better than others in prevalence rate and FPG, health education was better than others in 2PPG.

Medical intervention may focus on dietary intervention among pre-diabetes in China.

To assess the status of empowerment and mental state of type 2 diabetes patients and investigate the relationship between empowerment and mental state.

With the method of simple random sampling, 1 512 patients with type 2 diabetes mellitus (T2DM) from 18 hospitals of class 1, grade 3 general in Hunan province were investigated from January 2016 to April 2016. Questionnaires including general information questionnaire, Diabetes Empowerment Scale-DAWN Short Form, Problem Area in Diabetes-5 and World Health Orgabization-5 well-being index were used to evaluate the ability of empowerment and mental state in patients with type 2 diabetes and explored their relationship. Enumeration data were described by frequency and percentage, and measurement data were described by statistics. Measurement data didn′t conform to normal distribution, and single factor analysis was conducted by nonparametric test. Bivariate correlation was used to analyze the correlation among T2DM patients′ empowerment, emotional disorders and medical support. Stratified multiple regression analysis was used to analyze the influencing factors of T2DM patients′ mental status.

The mean score of empowerment ability, mood disorder, well-being for patients with type 2 diabetes mellitus was (53.20±16.40), (43.06±23.88) and (58.71±23.44), respectively. There were positive correlations between the empowerment ability and mood disorder in patients with T2DM (r=0.256), and the empowerment ability was negatively correlated with well-being (r=-0.078). Multivariate analysis showed that empowerment could independently predict 8.9% of emotional disorder variance (F=12.148, P<0.05) and 6.2% of happiness variance after controlling demographic confounding factors (F=5.182, P<0.05).

The higher the empowerment ability of patients with type 2 diabetes, the more serious their emotional disorders, and the less their happiness. In developing empowerment-based education and management programs for patients, attention should be paid to the scientific and effective of the methods, as well as to the changes in mental state of patients with type 2 diabetes.

To describe the clinical characteristics of a patient with maturity-onset diabetes of the young (MODY) type 6 (MODY6) and explore the molecular genetic mechanism.

The clinical data of a clinically suspected MODY patient was collected. The peripheral blood DNA was extracted from the patient. After next generation sequencing, Sanger sequencing was performed to verify the genetic test results. The function of genetic variation was predicted by genetic function software and protein structure was predicted by SWISS-MODLE. With other reported cases, we also reviewed and summarized the clinical feature of MODY6.

This study found a novel neurogenic differentiation 1 (NEUROD1) mutation (p. R103L) of MODY6, which was located in the DNA binding area, a basic helix-loop-helix domain, resulting in dysfunctional regulation of the insulin gene. Heterozygous NEUROD1 mutation had an incomplete penetrance of the phenotype, with a strong clinical heterogeneity. In addition, pregnancy might be an important time window for diagnosing MODY6. The NEUROD1 gene mutation was considered being a susceptible gene of type 2 diabetes in the previous reported Chinese family of NEUROD1 mutation.However, we reported the first Chinese case of MODY6 that met the typical MODY characteristics: diabetes on set before the age of 25, no evidence of insulin resistance and autoimmunity and three successive generations of diabetes in his family.

A novel NEUROD1 gene mutation is identified and its possible pathogenic mechanism is described. It is the first case of MODY6 in Chinese population that meets the typical MODY characteristics.

To investigate whether glucagon-like peptide-1 (GLP-1) can regulate lipid metabolism in hepatocytes by modifying forkhead box protein O1 (FoxO1) phosphorylation sites.

The hepatic carcinoma cell line HepG2 cells were used to construct the hepatic steatosis model. Measuring the change of intracellular triglyceride (TG) of the GLP-1 treated cells fatty liver model, Western blot was used to detect changes in phosphorylation of Thr24, Ser256, and Ser319 in FoxO1; construction and transfection of the FoxO1-Ser256 mutant plasmid, RT-PCR was used to detect the changes of ACC and Fasn genes regulated by FoxO1.

Compared with model group, ACC and Fasn mRNA level were lower than in GLP-1 treated model group, the difference was statistically significant (1.33±0.30 vs 4.21±0.66, 1.41±0.48 vs 3.05±0.67, t=5.31,4.16, all P<0.05). Compared with model group, the phosphorylation levels of ser256 and ser319 significantly elevated in GLP-1 group (t=7.34, 8.79, all P<0.05). After transfected with FoxO1-WT, the expression of ACC and Fasn mRNA were reduced in GLP-1 group (t=5.28, 4.33, all P<0.05). After transfected with FoxO1-MT, the expression of ACC and Fasn mRNA were not reduced in GLP-1 group (t=1.16, 2.51, all P>0.05).

GLP-1 may affect the expression of Foxol downstream gene ACC andFasn by modifying the phosphorylation sites of FoxO1, and reduce lipid formation in the fatty liver cell model.

The formulation of diabetes drug treatment strategies requires professional and standardized guidance, but the current clinical practice is far from meeting the needs of patients, and the development of artificial intelligence (AI) technology may become the solution. At present, the application of artificial intelligence in the formulation of diabetes drug treatment strategies can be divided into attempts in oral drugs and insulin therapy. Compared with the mature application of AI in insulin closed-loop control system, the research on assisting oral diabetes drug strategy formulation is relatively lagging behind. At present, the application of AI in the formulation of diabetes drug strategies is still in its infancy. It needs to be further improved in the accumulation of expert knowledge base, in-depth cooperation between medical and intelligent technologies, and later clinical practice testing. However, the development trend of AI is unstoppable.

In recent years, with the deepening of research on diabetic retinopathy (DR), the role of advanced glycation end products (AGE) and their receptors (RAGE) has been paid attention to. AGE and RAGE can induce apoptosis by damaging the function of retinal cells; Mediate microvascular injury, neovascularization and destruction of retinal pigment epithelial cells to mediate the development of DR. Inhibiting the production of AGE and RAGE, blocking their interactions and downstream signaling pathways have become potential targets for DR therapy.

The application of continuous glucose monitoring technology to carry out clinical research requires clinicians to understand and make rational use of various relevant parameters of continuous glucose monitoring. When the continuous glucose monitoring technology is the research object, the safety, effectiveness, economy and accuracy of continuous glucose monitoring can be studied; When continuous glucose monitoring technology is used as a research tool, cross-sectional studies can be carried out to study the characteristics of blood glucose fluctuations in different populations and disease states, and interventional studies can be used to evaluate the safety and effectiveness of various hypoglycemic regimens. The research of continuous glucose monitoring technology needs to be closely integrated with clinical work and complement each other.

With the development of society, the metabolic stress caused by energy excess has become an important reason for the continuous and rapid increase of the prevalence of type 2 diabetes mellitus (T2DM). Traditional hypoglycemic drugs mainly focus on the hypoglycemic effect itself. Therefore, drugs have different effects on energy metabolism, and even aggravate metabolic pressure, which makes the long-term efficacy poor. Sodium-glucose cotransporter (SGLT) -2 inhibitors are hypoglycemic drugs that can promote energy loss based on the mechanism of renal sugar excretion, significantly improve metabolic stress. At present, the mechanism related to multiple benefits of SGLT-2 inhibitors based on energy metabolism has not been completely clarified. This article interprets the efficacy and safety of SGLT-2 inhibitors in the treatment of diabetes from the metabolic perspective, and discusses the evidence and controversy of their diabetic ketoacidosis and the risk of genitourinary tract infection, so as to provide a reference for clinical in-depth understanding of the etiology of type 2 diabetes and rational use of SGLT-2 inhibitors.

Shu-Hsien Wang was one of the earliest Chinese Diabetologists. Based on 405 cases of diabetes mellitus in Peking Union Medical College Hospital, he conducted the first relatively large-scale retrospective case analysis of diabetes in China, which was published in two parts on the Chinese Medical Journal. A brief introduction and review of the first part of the essay was given in this article to honor Wang′s pioneering work and to shed light on the history of diabetology in China.