Volume 11 · Issue 03 · 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 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. This section briefly describes the real-world cross-sectional descriptive studies, interventional studies, high-quality prospective cohort follow-up studies and domestic basic diabetes research completed in the past ten years, as well as the progress of modern Chinese medicine intervention guided by traditional Chinese medicine theory or modern pharmacology. It is emphasized that Chinese diabetes scholars still need to continue to learn, digest and absorb advanced technologies and management concepts in terms of technology, and must face the reality in terms of management mode, combine national conditions, and explore a sustainable development road suitable for the long-term management of Chinese diabetic patients.

Advances in genomics, sequencing technology, metabolomics, proteomics, microbiomics, and big data analysis technology have driven the application of precision nutrition in patients with type 2 diabetes. This paper reviews the technical basis of precision nutrition practice and its significance in population dietary evaluation, as well as the research progress of therapeutic intervention and metabolic evaluation. Based on gene polymorphism research, metabolomics and flora research, the application of precision nutrition in the prevention and treatment of type 2 diabetes may become an important content of the development of nutrition science and have far-reaching health significance.

The intestinal flora is closely related to the occurrence of type 1 diabetes, or it is involved in the occurrence and development of type 1 diabetes by affecting the intestinal barrier function and regulating the intestinal immune system. Specific intestinal flora may be a predictor of type 1 diabetes. Vaginal delivery, breastfeeding, rational use of prebiotics and probiotics, and fecal transplantation may be able to prevent and treat type 1 diabetes by changing the composition of intestinal flora.

Gastrointestinal tract, as an important place for food digestion and absorption and the largest endocrine organ of human body, is crucial for maintaining metabolic balance. In recent years, it has been found that there are a wide range of taste receptors on the surface of gastrointestinal mucosa, which can detect taste signals of gastrointestinal contents. Activation of related receptors can induce intestinal hormone secretion, which in turn regulates gastrointestinal motility, appetite and postprandial blood glucose. The effects of intestinal bitter taste receptors on gastrointestinal hormones, blood glucose, gastric emptying and appetite were reviewed.

Diabetic foot is one of the main causes of disability and death of diabetic patients. Based on the principle of "Chinese practice, Chinese evidence and Chinese guidelines", the Diabetology Branch of Chinese Medical Association, together with the Infectious Diseases Branch of Chinese Medical Association, the Tissue Repair and Regeneration Branch and other multidisciplinary experts in related fields, jointly formulated this clinical guideline suitable for the current situation of diabetic foot in China, aiming at standardizing the prevention, diagnosis and treatment of diabetic foot in China. This guideline has the following features: (1) highlighting clinical practicality; (2) Chinese evidence fully incorporated in the field of diabetic foot; (3) Pay attention to early screening and management, emphasizing that prevention of diabetic foot is better than treatment; (4) Emphasize the importance of standardized and comprehensive management; (5) Emphasize the multidisciplinary collaborative diagnosis and treatment of diabetic foot. In addition, with reference to the requirements of the 2017 version of China's Type 2 Diabetes Prevention and Treatment Guidelines, key points and evidence levels have been added, and the evidence levels are divided into three levels: A, B and C according to evidence quality, clinical significance, universality and applicability. Grade A: Evidence based on multiple randomized clinical trials or meta-analyses. Grade B: Evidence based on a single randomized clinical trial or multiple non-randomized controlled studies. Grade C: Expert consensus opinion only and/or based on results from small-scale studies, retrospective studies, and registered studies.

To investigate the efficacy and safety of dapagliflozin versus linagliptin in overweight or obesity type 2 diabetic patients with poor glycemic control of oral antidiabetc drugs.

T2DM patients with body mass index (BMI) >25 kg/m ², glycosylated hemoglobin A_1c (HbA_1c) 7.5%-9.0% were recruited in this randomized, open-labelled, parallel-group study from March 2017 to January 2018 in the Department of Endocrinology, Quanzhou First Hospital Affiliated Fujian Medical University. A total of 141 subjects (74 males and 67 females) with a mean age of (49.5±11.8) years who received metformin (at least 1 500 mg/d) and sulfonylureas (at least half of the maximal dose) for at least 3 months were randomly assigned to 2 groups: additional 24-week treatment of dapagliflozin 10 mg once a day (n=71) or linagliptin 5 mg once a day (n=70). HbA_1c, plasma glucose, body weight, blood pressure, lipid profiles, serum uric acid, urinary albumin/creatinine and adverse events at baseline and after 24 weeks were evaluated. Statistical analysis was performed using t-test, Mann-Whitney U test and Chi-Square test for different data.

Compared with the data of baseline, HbA_1c decreased 1.2%±0.4% in dapagliflozin group (8.6%±0.4% to 7.4%±0.5%) and 0.9%±0.4% in linagliptin group (8.5%±0.4% to 7.6%±0.6%) (t=3.61, P=0.00) respectively after 24-week treatment. The proportion of patients with HbA_1c less than 7.0% were 53.5% (38/71) and 34.2% (24/70) in dapagliflozin group and linagliptin group (χ²=5.32, P=0.02), respectively. The reduction of body weight from baseline to week 24 was significantly greater in dapagliflozin group with a decrease of 2 (1.1, 2.0) kg than that in linagliptin group with a decrease of -0.3 (-0.5,0) kg (Z=-9.50, P=0.00). After 24-week treatment, SBP decreased (8.0±6.3) mmHg (1 mmHg=0.133 kPa) in dapagliflozin group and (1.0±3.0) mmHg in linagliptin group respectively, the difference was statistically significant (t=7.93, P=0.00); DBP decrease (2.5±2.4) mmHg in dapagliflozin group and (1.0±1.8) mmHg in linagliptin group respectively, the difference was statistically significant (t=3.91, P=0.00). After 24-week treatment, the occurrence of hypoglycemia was similar in dapagliflozin and linagliptin groups [14.1% (10/71) vs 12.9% (9/70), χ ²=0.05, P=0.51]. A female urinary tract infection and a male genital infection were reported in dapagliflozin group.

Both dapagliflozin and linagliptin treatment are effective in overweight or obesity type 2 diabetic patients with poor glycemic control of oral antidiabetic drugs. Dapagliflozin is better than linagliptin in controlling of plasma glucose, body weight and blood pressure, and the safety of two groups is similar.

To investigate the association of carotid intima-media thickness (CIMT) with abnormal glucose and central obesity.

A total of 10 207 community residents 40 years of age or older who attended the Chinese patients with Type 2 Diabetes Cancer Risk Epidemic Studies from August 16, 2011 to December 10, 2011. There were 9 556 cases elected according to inclusion and exclusion criteria. Waist, waist-to-hip ratio, body mass index and blood pressure were measured. Fasting plasma glucose, postprandial 2 hours blood glucose, glycosylated hemoglobin, high-density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides and blood uric acid were tested. CIMT was evaluated by neck vascular color Doppler ultrasonography. Respectively compare males and females carotid intima-media thickness in the quartile groups which made by waist circumference. The residents were divided into four groups: normal group (n=955), central obesity group (n=3 919), abnormal glucose group (n=465) and central obesity and abnormal glucose group (n=4 217). Single factor analysis of variance was used to compare the CIMT of each group. Pearson correlation analysis was performed for the correlation between waist circumference, HbA_1c and other indicators and CIMT. The optimal cutoff point of carotid endarteral thickening screening was analyzed by using receiver operating characteristic (ROC) curve.

(1) The CIMT values were (0.95±0.18), (1.00±0.17), (1.02±0.19), and (1.06±0.17) cm for normal group, central obesity group, abnormal glucose group, and central obesity and abnormal glucose group, respectively. CIMT level of central obesity abnormal glucose group was statistically higher than other three groups (F=156.57, P<0.001). (2) CIMT were positively correlated with waist circumference and HbA_1c (r=0.209, r=0.186, P<0.001) with Pearson test. Multiple stepwise regression showed that there was a positive correlation between CIMT and waist circumference and HbA_1c after adjusted for age, fasting plasma glucose, systolic blood pressure, LDL-C and uric acid (P<0.01). HDL-C and diastolic blood pressure were negatively correlated with CIMT (P<0.001). The areas under the receiver operating characteristic curve for predicting CIMT thickening with waist circumference were 0.615 and 0.604 in male and female, which was statistically significant (P<0.001). When waist circumference was 92.3 cm in male and 89.5 cm in female, the sensitivity was 47.7% and 57.2%, while as specificity was 68.9% and 57.6%, the Youden index was 0.166 and 0.148. The areas under the ROC curve for waist circumference combined HbA_1c as a predictor of abnormal CIMT were 0.659 and 0.642 in male and female with sensitivity at 57.3% and 37.7% and specificity 63.3% and 41.0% respectively.

The CIMT values are significantly increased in the central obesity group and abnormal glucose group. There is significant correlation between waist circumference and CIMT, waist circumference and HbA_1c are the independent risk factors for atherosclerosis. Waist circumference can be used to screen high-risk group with CIMT thickening.

To evaluate the safety and tolerability of linagliptin as monotherapy, combined with metformin or combined with metformin and sulfonylurea in patients with type 2 diabetes mellitus (T2DM).

A total of 4 789 diabetes patients from 17 randomized clinical trials were included in this pooled analysis. Patients eligible for inclusion criteria with treatment naïve or metformin monotherapy or metformin combined with sulfonylurea at baseline were selected. Individual data were collected and analyzed to evaluate the safety and tolerance of linagliptin.Subgroup analysis was carried out according to the classification of the original research program. Continuous variables were compared between groups using t-test or one-way analysis of variance.

A total of 4 789 diabetes patients were included in this pooled-analysis, 3 343 patients in linagliptin group (including monotherapy, combined with metformin or combined with metformin+ sulfonylurea), and 1 446 patients in the placebo group. The incidence of adverse events was similar (52.4% vs 52.9%) in linagliptin vs placebo. The hypoglycemia event number in linagliptin was slightly higher than placebo (229 vs 59, OR=1.46, 95%CI 1.06-2.00). In patients with sulfonylureas as background treatment, the number of hypoglycemia event was slightly higher in Linagliptin group than that in placebo group (207 vs 49, OR=1.66, 95%CI 1.17-2.34), while in patients without sulfonylureas, hypoglycemia event was similar between the two groups (22 vs 10, OR=0.73, 95%CI 0.33-1.61). In addition, the risk of cardiovascular disease was similar between linagliptin and placebo (OR=1.19, 95%CI 0.88-1.62), and in sub-group analysis with ages, eGFR or body mass index (4.9% in the ligliptin group and 4.3% in the placebo group) as well. In addition, the number of adverse event confirmed by the clinical events committee was very low in both linagliptin and placebo (0.2% of patients in the ligliptin and placebo groups had cardiovascular death, myocardial infarction or stroke complex endpoints, and 0.3% of both group with cardiovascular death, myocardial infarction, stroke or unstable angina complex endpoints).

Based on this pooled analysis, linagliptin is a good treatment option for patients with type 2 diabetes with good safety and tolerance.

To characterize the clinical and molecular features of a patient with maturity onset diabetes of the young (MODY)5 caused by S148L mutation in hepatocyte nuclear factor 1β (HNF-1β) .

The proband was a 23-year-old male with diabetes onset at ten. At that time, a random blood glucose level of 38 mmol/L and hemoglobin A_1c level of 17.6% were detected. Renal insufficiency and renal dysplasia were present at the same time. There′s no family history of diabetes or renal disease in the pedigree. Although the islet cell antibody was negative, he was diagnosed as type 1 diabetes mellitus (T1DM) on account of low C-peptide level. During the follow up, azoospermia, cysts of seminal vesicle and bilateral acute hydronephrosis occurred. MODY-related genes of the proband and his father as well were sequenced using next-generation sequencing. Literature review was conducted for previously reported cases with the same mutation in HNF-1β.

A mutation in the HNF-1β gene S148L (c.443>T) in exon 2 was identified in the proband, but not in his father. Literature review revealed that there were two mutations S148L and S148W reported in eight cases. Seven of the eight probands had S148L mutation. Renal involvement and early-onset diabetes are typical characteristics of most subjects affected by S148L mutation. Some of them had low birthweight or pancreatic malformation and six cases were the first patients in the family.

Congenital renal abnormality, early-onset of diabetes before age of 25 years and with negative T1DM antibodies probably are important clues for diagnosis of MODY5. Therefore, T1DM antibodies negative juvenile diabetes patients accompanied by abnormalities in kidney, pancreas and genital organs should be suspected for MODY5, even those without family history.

To investigate the protective role of chloroquine preconditionning in hypoxia/reoxygenation injury in HK-2 cells exposed to high glucose.

HK-2 cells were randomly divided into three groups (n=6): high glucose group (HG), high glucose+ hypoxia/reoxygenation group (HH/R), high glucose+ hypoxia/reoxygenation+ chloroquine preconditionning group (HH/R-CQ). The high glucose and hypoxia/reoxygenation model was established by sequential treatment of 30 mmol/L glucose for 72 h, hypoxia 4 h and reoxygenation 2 h. Chloroquine (50 μmol) was given at the beginning of high glucose treatment. Cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) were used to evaluate cell viability. Enzyme-linked immunosorbent assay was used to detect interleukin (IL)-6 and tumor necrosis factor (TNF)-α. The flow cytometry was used to detect the ratio of apoptosis. The immunofluorescence and the western blot were used to detect Toll-like receptor 7 (TLR7), myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB). Data were analyzed by t test.

Compared with group HG, CCK-8 was decreased, LDH, IL-6, TNF-α, the ratio of apoptosis, TLR7 (0.635±0.034 vs 0.857±0.052,t=4.77, P<0.05), MyD88 (0.607±0.029 vs 0.828±0.040, t=5.36, P<0.05) and NF-κB (0.618±0.035 vs 0.854±0.024,t=5.62, P<0.05) were increased in group HH/R; Compared with group HH/R, CCK-8 was increased, LDH, IL-6, TNF-α, the ratio of apoptosis, TLR7 (0.857±0.052 vs 0.642±0.024,t=4.61, P<0.05), MyD88 (0.828±0.040 vs 0.638±0.050, t=4.60, P<0.05) and NF-κB (0.854±0.024 vs 0.605±0.035,t=5.94, P<0.05) were decreased in group HH/R-CQ.

TLR7/MyD88/NF-κB pathway involved in the hypoxia/reoxygenation injury in high glucose. Chloroquine decreased the hypoxia/reoxygenation injury by reducing inflammatory response and cell apoptosis via inhibiting TLR7/MyD88 pathway.

Recent studies have consistently shown that the gut microbiota is a new and potential driver in the pathophysiology of type 2 diabetes mellitus (T2DM), interacting with obesity, low-grade inflammation, insulin resistance and T2DM, and may even play a key hub role in it. In addition, human intestinal microorganisms can not only affect brain function and change host behavior through the microbial-intestinal-brain axis, but also promote host metabolism and health, such as weight loss, fat loss, blood sugar control and insulin sensitivity. This has also become a promising target for the treatment of related diseases such as T2DM.

The newly developed flash glucose monitoring (FGM) system realizes the humanized iteration of blood glucose monitoring technology. The connected enzyme technology used in its sensor has the characteristics of stable signal, low potential start-up, strong anti-interference ability, and glucose reaction does not depend on oxygen. At the same time, the restricted outer membrane used by the sensor can improve the biocompatibility of the sensor-tissue interface and enhance the bio-mechanical properties of the sensor. Therefore, the sensor probe is not easy to trigger the inflammatory reaction of the body, which ensures the stable operation of the sensor for a long time. These two core technologies enable FGM to realize the upgraded calibration method of sensor factory calibration, avoiding the pain and deviation caused by traditional CGM requiring patients to frequently collect fingertip blood for calibration, and maintaining the accuracy of FGM products throughout the wearing period and during the shelf life.