Volume 13 · Issue 05 · 2021

Diabetic foot ulcer (DFU) not only affects the quality of life of patients, but also poses a challenge to China's healthcare system. The contents of modern DFU care include debridement, use of dressings to promote wet healing of wounds, decompression, vascular assessment and management, treatment of infections and blood sugar control. The standard of care for diabetic foot ulcers recommended by the International Diabetic Foot Working Group (IWGDF) includes glycemic control, vascular assessment and restoration of vascular perfusion, infection control, foot decompression, and wound care. Multidisciplinary collaboration model and rapid referral pathway have also made great progress in DFU treatment in recent years.

Foot ulcer is one of the main complications of diabetes, with high morbidity, mortality and resource utilization. The main objective of prophylactic treatment of diabetic foot is to correct the modifiable foot ulcer risk factors. Measures to correct modifiable risk factors include structured education for patients, structured education for medical staff, foot self-management behaviors, treatment of pre-ulcerative foot lesions or other clinical symptoms of the foot, orthopedic interventions, and foot-related exercises, among others.

Prevention of foot ulcer is the key to reduce the amputation rate of diabetic patients and reduce the medical burden and care burden of patients and their families. The author excerpted and interpreted the article "The future of diabetic foot ulcer prevention: the mode transformation from hierarchical medicine to individualized medicine". The authors emphasize that the control of diabetic foot should be shifted from priority treatment to priority prevention, point out many obstacles in prioritizing the prevention of foot ulcer in research and clinical practice, and discuss the importance and feasibility of individualized medicine for the prevention of diabetic foot ulcer. The paradigm shift from hierarchical medicine to individualized medicine is a current comprehensive solution to overcome these barriers, and it is also a new trend in the development of diabetic foot ulcer prevention.

To investigate the overall state of the glycemic control in children with type 1 diabetes mellitus (T1DM) in a single center and analyze the related factors.

This cross-sectional clinical-based research was conducted among patients under 18 years old diagnosed with type 1 diabetes (the duration of diabetes>3 months) from the Diabetes Clinic of Beijing Children′s Hospital from January 2015 to December 2019. The patients were required to receive a follow-up every 3 months. The follow-up data of the same patient were collected once a year. Glycosylated hemoglobin (HbA_1c) was taken as the main research index (the selection principle was the median glycosylated hemoglobin per year). Demographic data included age at onset and at follow-up, sex, duration of diabetes, years of follow-up. In addition, clinical information on weight, height, modalities of insulin treatment (number of injections or pump therapy), the frequency of self-monitoring of blood glucose (SMBG) per day or using of continuous glucose monitoring (CGM)/flash glucose monitoring (FGM) were collected. According to the years of follow-up, the patients were divided into 5 groups. According to the HbA_1c control target (7.0%), the patients were divided into the good-control group (HbA_1c<7.0%) and the poor-control group (HbA_1c ≥7.0%). According to the age of the patients, they were divided into three groups (<5 years old group, 5 to 10 years old group and>10 years old group). The general situation of blood glucose control from 2015 to 2019 was compared by groups, and the related factors were analyzed by linear regression and two-level logistic regression.

A total of 1 976 patients with T1DM were collected (2015 n=362, 2016 n=410, 2017 n=415, 2018 n=384, 2019 n=405), the age was 10.09 (7.18, 12.85) years old; the duration of diabetes was 1.94 (0.88, 3.86) years, 49.5% (978/1 976) were male. There was no significant difference in age, sex and duration of disease among each groups (P>0.05),and comparable. HbA_1c decreased from 7.4%(6.7%, 8.3%) in 2015 to 6.8%(6.1%, 7.6%) in 2019 (P<0.01). The rate of achieved A_1C target increased year by year [34.5%(125/362), 42.0%(172/410), 47.0%(195/415), 55.2%(212/384) and 56.3%(228/405), respectively], and the difference was statistically significant (Z=7.02, P<0.01). The HbA_1C was positively correlated with age and duration of disease (r=0.095, 0.170 respectively, P<0.01). Logistic regression analysis showed that older of age, longer duration of disease and less frequency of daily blood glucose monitoring were the risk factors of failing to achieve HbA_1c target.

From 2015 to 2019, HbA_1c in children with T1DM has decreased year by year, and the rate of achieved A_1C target has increased year by year, and it has increased by 1.63 times in 2019 compared with 2015. The increase in the use of CGM/FGM is the main factor to improve blood glucose control.

To establish a new threshold of prostate-specific antigen (PSA) for early warning of prostate cancer (PCa) among people with type 2 diabetes mellitus (T2DM).

We retrospectively analyzed the clinical data of 2 151 patients who underwent prostate biopsy for the first time admitted to Shanghai Tenth People′s Hospital from January 2012 to December 2018. Taking the positive pathological results of prostate biopsy as the gold standard, all patients were divided into T2DM group and non-T2DM group for comparison. Among them, patients with PCa were divided into PCa-T2DM group and PCa-non-T2DM group. Using the method of big data analysis and machine learning, a new PSA threshold for early warning of PCa in the T2DM population (the original threshold 4.0 ng/ml) was obtained, and its sensitivity and specificity were calculated. Probability function fitting was used to estimate the distribution of PSA levels in the overall population, support vector machine was used to calculate the new threshold, and receiver operating characteristic (ROC) curve was used to test its diagnostic efficacy.

The detection rate of PCa in 2 151 patients was 35.89% (772/2 151). All subjects were divided into T2DM group (496 cases, 23.06%) and non-T2DM group (1 655 cases, 76.94%). The PSA of the T2DM group was lower than that of the non-T2DM group, and the difference was statistically significant (P<0.01). The new PSA threshold for PCa screening for T2DM population was 3.27 ng/ml. In the T2DM group, with 3.27 ng/ml of PSA as the diagnostic cut-off point, the area under the ROC curve was 0.83, and the diagnostic sensitivity and specificity were 94.53% and 41.36%, respectively. In the overall population, with 4 ng/ml of PSA as the diagnostic cut-off point, the area under the ROC curve was 0.83, and the sensitivity and specificity were 91.54% and 46.78%, respectively. There was no statistically significant difference between the two groups (P>0.05).

The serum PSA levels in T2DM patients reduced. The new PSA threshold (3.27 ng/ml) for type 2 diabetes mellitus has a better early warning effect on prostate cancer, which is conducive to improving the early diagnosis rate of prostate cancer in T2DM patients.

To explore the correlation between the different glycemic variability (GV) indices calculated by self-monitoring of blood glucose (SMBG) and mean amplitude of glycemic excursion (MAGE) obtained from the continuous glucose monitor (CGM) system in patients with type 2 diabetes mellitus (T2DM).

This was a retrospective study. We analyzed the data of T2DM patients who received 48-72 h CGM and 7-point SMBG (pre-and post-breakfast, lunch, dinner and prior to bedtime) simultaneously in Department of Endocrinology and Metabolic Disease, the Third Affiliated Hospital of Sun Yat-sen University from January 2018 to October 2019. The GV indices calculated from the 7-point SMBG data included the standard deviation (SDBG) of the 7-point glucose profiles, the largest amplitude of glycemic excursions (LAGE) and the postprandial glucose excursion (PPGE), coefficient of variation of blood glucose (CV) and mean amplitude of glucose excursion (MAGE′, calculated by SMBG profile). Spearman′s correlation analysis, simple linear regression and multiple stepwise regression analysis were used to analyze the relationship between the different GV indices calculated from 7-point SMBG and MAGE obtained by CGM, and the receiver operator characteristic (ROC) curve was drawn to evaluate the ability of the former to predict the latter.

Among 105 patients with T2DM, the SDBG, PPGE, LAGE and CV calculated by 7-point glucose profiles of SMBG were (2.02±0.77) mmol/L, (2.75±1.13) mmol/L, (5.62±2.13) mmol/L and (25.92±0.77)%, respectively, while the level of MAGE′ and median MAGE were 4.11 (2.84, 5.92) mmol/L and 4.00 (2.65, 5.00) mmol/L, respectively. SDBG, PPGE, LAGE, CV and MAGE′ were significantly correlative with MAGE (r=0.614, 0.499, 0.588, 0.533 and 0.473, respectively, all P<0.01). Multiple stepwise regression analysis was performed with MAGE as dependent variable and SDBG, PPGE, LAGE, CV and MAGE′ as independent variables, and only SDBG entered the equation (P<0.01). The areas under ROC curve for SDBG [0.795, 95% confidence interval (CI) was 0.708-0.882], LAGE (0.782, 95%CI was 0.692-0.872) and CV (0.769, 95%CI was 0.677-0.846) were larger than those for PPGE (0.718, 95%CI was 0.620-0.816) and MAGE′ (0.704, 95%CI was 0.607-0.789, allP<0.01) in reflecting the unqualified MAGE.

GV indices calculated from 7-point SMBG data including SDBG, LAGE, PPGE, CV and MAGE′ are positively correlated with MAGE obtained from CGM. And SDBG has higher accuracy than the other four parameters.

To explore the effects of glucagon-like peptide-1 (GLP-1) therapy on the expression of growth different factor 15(GDF15) in hepatocytes of non-alcoholic fatty liver disease (NAFLD).

A total of 25 patients with NAFLD and type 2 diabetes mellitus were analyzed (liraglutide group, 9; insulin glargine group, 8 and sitagliptin group, 8). The level of serum GDF15, intrahepatic lipid (IHL), body weight, and body mass index (BMI) were collected at baseline and week 26. IHL of patients was quantified by magnetic resonance imaging-estimated proton density fat fraction. Male C57BL/6 mice challenged with a high-fat diet for 12 weeks were treated with exenatide (GLP-1 group, n=6) or normal saline (HFD group, n=6) by intraperitoneal injection. Another group with a chow diet was designed as normal control (n=6). Liver tissue were collected after 8 weeks of intervention. Human HepG2 cells were incubated in medium containing 300 μmol/L sodium palmitate (PA) and treated with Exendin-4 (0 nmol/L, 1 nmol/L, 20 nmol/L, 100 nmol/L, respectively). 10% bovine serum albumin was set as the control group. GDF15 knockout stable cell line constructed by using CRISPR/Cas9 system, and empty vector served as a negative control. Transfected cells were incubated in medium containing 300 μmol/L PA and treated with or without 100 nmol/L Exendin-4. The levels of GDF15 released into serum or cell supernatant and relative mRNA levels of GDF15 in hepatic tissue or HepG2 cells were detected. Statistical analysis was mainly performed using one-way analysis of variance (ANOVA), covariance analysis, Pearson correlation coefficients.

No significant changes in the level of serum GDF15 was observed in the sitagliptin and insulin glargine groups after 26-week therapy. However, the level of serum GDF15 increased significantly in the liraglutide group [(742.2±279.0)vs. (920.3±265.4) pg/ml, P=0.015], and weight, BMI and IHL decreased statistically significant [(80.4±6.3) vs. (76.9±7.2) kg; (29.0±2.2) vs. (27.8±1.9) kg/m²; (18.3±7.4)% vs. (12.2±5.5) %; respectively] (all P<0.05). Furthermore, negative correlation was found between the change in serum GDF15 and IHL in the liraglutide group (r=-0.676, P=0.045). We found that hepatic steatosis and inflammation in the liver, which were improved markedly in the HFD group, reduced in GLP-1 group. Relative mRNA levels of GDF15 in liver tissue of mice were remarkably higher in the GLP-1 group than those in HFD group and control group. In addition, GLP-1 alleviated lipid deposition in HepG2 cells, which induced by PA, and elevated the expression and secretion of GDF15 in a dose-dependent manner. Compared with the negative control, GDF15 knockout abolished the effect of GLP-1 on alleviation of triglyceride accumulation and inflammation.

GLP-1 could up-regulate the expression and secretion of GDF15 and alleviatehepatic steatosis and inflammation of NAFLD.

To explore the establishment of a novel rat model of diabetic retinopathy (DR) and its pathological characteristics.

Thirty-six Brown Norway (BN) rats were divided into the control group (n=12), streptozocin (STZ) group (n=12) and STZ+spermidine (SP) group (n=12). STZ group and STZ+SP group received tail vein injection of STZ. STZ+SP group received vitreous injection of SP, and the control group received vitreous injection of the same volume of solvent. The rats continued to feed for 12 weeks after modeling, during which weight and fasting blood glucose were monitored. The ultrasound imaging system was used to image the central retinal artery to observe the retinal blood supply. After sacrificed, the eyes were enucleated for hematoxylin-eosin staining to observe the basic structure of the retina, to analyze the thickness of each layer. Retina digestive preparations were for periodic acid-schiff staining and glial antigen 2 immunofluorescent staining to observe the microvessels and pericytes, respectively. Retinal reactive oxygen species (ROS) levels were observed by flow cytometry. Finally, the claudin-1 and occludin mRNA expressions in the retina tissue were detected by real-time polymerase chain reaction and the protein expressions were assessed by automatic protein quantification technology. Repeated measurements analysis of variance was used to compare among multiple groups, and LSD-t method was used to compare between two groups.

Compared with the control group, the STZ group and the STZ+SP group had significantly decreased body weight (P<0.05) and increased blood glucose (P<0.05) during the experiment. Compared with the STZ group, peak systolic velocity and end diastolic velocity of the central retinal artery in the STZ+SP group were markedly reduced (P<0.05), while pulsatility index and resistance index were obviously raised (P<0.05), the differences were statistically significant. Pathological observations showed that the arrangement of the neuronuclear layer was loose and disordered, and the retinal plexus area was edema in the STZ group and the STZ+SP group, moreover, the STZ+SP group performed more seriously. Compared with the STZ group, the thickness of the retina and the thickness of the outer plexus/total thickness of the retina were increased significantly in the STZ+SP group (P<0.05), and the loss of capillary pericytes and the formation of acellular capillaries were also distinctly increased. Compared with the control group and the STZ group, ROS levels in the STZ+SP group were increased significantly (P<0.05). Compared with the control group, the expressions of claudin-1 and occludin mRNA in the retina of the STZ+SP group were decreased significantly (P<0.05), as well as the corresponding protein expressions (P<0.05), the differences were statistically significant.

A severe animal model of DR lesions is established via tail vein injection of STZ combined with vitreous injection of SP in BN rats. The lesions are characterized by more severe decrease of retinal vascular compliance, reduction of blood flow supply, retinal edema, formation of a large number of new acellular capillaries and the increased apoptosis of retinal capillary pericytes.

We analyzed the clinical data and genetics of a patient with first-onset diabetes and his family, and found that he had a typical family history of 3 generations. The onset of diabetes in his family was early, and the treatment was independent of insulin. The amino acid at position 379 of the hepatocyte nuclear factor-1 α gene changed from proline to serine (P379T), thus confirming that he was diagnosed as adult-onset diabetes mellitus (MODY) type 3 in adolescents with special types of diabetes. Through this case, we summarize the recent advances in the classification of diabetes mellitus, screening, diagnosis, differential diagnosis and treatment of MODY. The aim is to improve the ability of endocrinologists to diagnose and treat MODY, so that patients and families can get early diagnosis and early benefits.

Pregnancy complicated diabetes, including pre-pregnancy diabetes and gestational diabetes, is a common complication of pregnancy, which not only threatens maternal health, but also has many adverse effects on the health of future generations in the near and long term. This paper mainly summarizes the influence of pregnancy complicated by diabetes on the long-term health of offspring, analyzes the pathogenesis and clinical treatment of pregnancy complicated by diabetes on the long-term health of offspring, and introduces the related research progress.

Sexual dysfunction is one of the complications of diabetes. In recent years, with the increasing incidence of diabetes, the prevalence of sexual dysfunction is also increasing. Due to many reasons such as cultural and social concepts, the proportion of women seeking medical treatment due to sexual function problems in China is low, and there is less attention to diabetic female sexual dysfunction (FSD) in clinic, and related research is insufficient. This paper reviews the epidemiology, pathogenesis and related risk factors of diabetic FSD.

Mitochondrial diabetes, also known as maternal diabetes with deafness (MIDD), is able to affect 3% of diabetic patients, and about 85% of MIDD is associated with m.3243A>G mutations. The clinical manifestations of MIDD are diverse, and the diagnosis and treatment are difficult. This article reviews the characteristics, diagnosis, evaluation and treatment of m.3243A>G mutation-related MIDD with the latest evidence, in order to provide support for the clinical response of MIDD.

Digestive symptoms are more common in diabetic patients, which can involve the whole digestive tract from the mouth to the anus, seriously affecting the patient's quality of life and blood sugar control. Because diabetes lacks specific gastrointestinal symptoms, and a variety of hypoglycemic drugs can cause gastrointestinal adverse reactions, it is necessary to rule out other related causes before diabetic gastrointestinal symptoms can be diagnosed. At present, the treatment of diabetes-related gastrointestinal symptoms mainly focuses on improving the symptoms, but the treatment effect is often poor. In this article, we will summarize the clinical manifestations, mechanisms and management measures of main digestive tract symptoms in diabetic patients, so as to provide new ideas for future clinical diagnosis, treatment and research directions.

Umbilical cord mesenchymal stem cells (MSCs) have the same genetic material as the offspring and are sensitive to the external environment, which can be used to evaluate the long-term effects of various factors on the early development of offspring. More and more studies have proved that there are abnormal phenotypes in umbilical cord MSC from obese women and women with abnormal glucose metabolism. We focused on the effect of abnormal glucose metabolism during pregnancy on the function of umbilical cord MSC.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by progressive destruction of islet beta cells. CD4⁺and CD8⁺All memory T cells play an important role in the pathogenesis of T1DM, especially CD8 cells⁺T cells are considered to be the key T cells that mediate beta cell destruction. The persistence of autoreactive memory T cells is thought to be the main cause of the persistence of chronic inflammation in T1DM. Autoreactive T cells in patients with T1DM are mainly effector memory cells. It has been found that islet beta cell function can be protected by clearing or regulating autoreactive T cells. Immunotherapy methods involved in memory T cell in T1DM immunotherapy include T cell clearance, clearance and inhibition of dynamic equilibrium cytokines, blocking of costimulatory factors on T cell surface, inhibition of Kv1.3 channels, etc. These immunotherapy methods have an effect on memory T cell subsets.

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease, and its pathophysiological mechanism is still unclear. As the course of diabetes prolongs, cardiovascular complications are the leading cause of death. Intestinal flora is the largest micro-ecosystem in human body, which has an important influence on human body material and energy metabolism. The intestinal flora characteristics of patients with T2DM complicated with cardiovascular complications were reviewed in order to understand the ideas and methods of disease prevention and treatment based on intestinal flora.

Persistent non-union of diabetic foot ulcer (DFU) wounds is an important cause of amputation and even death in diabetic foot patients. Dressing application is a key part of the treatment of DFU. Modern dressings have made some progress in the application of DFU wounds, and recent high-quality evidence recommends the use of new evidence-based treatment modalities, such as sucrose octasulfate dressings. This paper introduces the kinds, characteristics and research progress of modern dressings in recent 10 years.