Volume 12 · Issue 11 · 2020

Diabetic macrovascular complications are the primary cause of disability and death in patients with type 2 diabetes, which seriously affect the quality of life of patients, and deserve high attention. With the announcement of the results of large-scale evidence-based studies, the concept of prevention and treatment of diabetic macrovascular complications has been iteratively updated, gradually changing from "hypoglycemic as the center" to a comprehensive management and prevention model of "controlling blood sugar and improving cardiovascular events and death outcomes". Although new glucose control evaluation indexes such as the time of blood glucose within the target range (TIR) have appeared in recent years, at present, glycosylated hemoglobin (HbA_1c) As a key indicator to assess the risk of diabetic complications, its importance remains unshakable. The cardiovascular outcome study (CVOT) of new hypoglycemic drugs has brought a new dawn to diabetic patients, which has prompted its clinical application status to rise sharply, but there is still room for further exploration and analysis.

The diagnostic basis of diabetes determines that blood sugar control is the primary task of diabetes treatment. Reducing blood sugar can eliminate the symptoms of hyperglycemia, prevent acute metabolic disorders, improve the quality of life of patients, and prevent and treat complications of microvascular disease. Improving the prognosis of atherosclerotic cardiovascular disease (ASCVD) in diabetic patients must comprehensively control the risk factors for cardiovascular disease. Some hypoglycemic drugs, glucagon-like peptide 1 receptor agonists or sodium-glucose cotransporter 2 inhibitors, can improve and delay ASCVD, heart failure and chronic kidney disease outside hypoglycemic effects, and provide a new choice for improving the prognosis of patients with type 2 diabetes.

Atherosclerotic cardiovascular disease (ASCVD) is an important chronic complication of diabetes. In the past, ASCVD mainly focused on coronary heart disease, but less attention was paid to stroke, which has a higher incidence in China. Diabetic stroke has a higher mortality and disability rate than non-diabetic, and comprehensive management strategies can reduce the incidence of diabetic stroke and improve the prognosis. This article mainly deals with the epidemiology, clinical characteristics, pathophysiology, comprehensive strategy of primary prevention of diabetic stroke, and blood glucose management in acute and chronic stroke.

To analyze the harm of diabetic lower extremity arterial disease and diabetic foot, interpret the results and clinical significance of the Chinese type 2 diabetes mellitus (T2DM) lower extremity arterial disease screening study (China-DiaLEAD), introduce the risk factors, prevention and treatment status of T2DM lower extremity arterial disease (LEAD) in China and the preliminary risk assessment model of T2DM LEAD patients, promote the early diagnosis and treatment of T2DM LEAD patients in China, and provide evidence for the update of relevant guidelines.

Microcirculation disorder is one of the important pathophysiological bases of diabetic peripheral neuropathy (DPN). Poor blood glucose control in diabetic patients can lead to vascular structural changes such as thickening of microvascular basement membrane, swelling and proliferation of endothelial cells and increased vascular permeability, accompanied by vasodilation dysfunction and hemorheology abnormalities. These changes in microcirculation can lead to the occurrence and development of DPN by triggering energy metabolism disorders, sorbitol accumulation, inositol depletion and abnormal increase of oxidative stress. Drugs such as prostaglandin E1, prostacyclin derivatives, and pancreatic kininogenase and phosphodiesterase inhibitors can improve microcirculatory disorders, increase blood perfusion of nerve tissue, and alleviate ischemic and hypoxic damage of nerve tissue through different mechanisms.

To compare atherosclerotic lesions between adults with type 1 and type 2 diabetes, and carotid with lower extremity atherosclerosis as well.

This observational study was carried out in 192 adults with type 1 diabetes and 196 adults with type 2 diabetes (age ≥ 18 years old). Based on Doppler ultrasound, atherosclerotic lesions including intima-media thickness, plaque and stenosis were compared between adults with type 1 and type 2 diabetes. Furthermore, carotid and lower extremity atherosclerosis were compared as well.

After adjustment for age, gender, and diabetes duration, the carotid intima-media thickness in adults with type 2 diabetes was significantly greater than that in adults with type 1 diabetes [(0.83±0.19)vs(0.76±0.17) mm, t=4.882, P<0.05]. The percentage of carotid plaque and stenosis (48.0% and 9.2%, respectively) in type 2 diabetes were significantly higher than those in type 1 diabetes (χ²=24.319, 5.828, all P<0.05, respectively). The prevalence of lower limb plaque (χ²=4.314, 18.559, all P<0.001 for type 2 diabetes) and stenosis (χ²=6.534, 4.493, all P<0.05 for type 2 diabetes) were significantly higher than that of carotid plaque and stenosis in adults with type 1 and in type 2 diabetes, respectively.

Atherosclerotic lesions in adults with type 2 diabetes are more severe than that in adults with type 1 diabetes. Furthermore, lower limb atherosclerotic lesions are more severe than carotid atherosclerotic lesions in adults with diabetes. The combination of carotid and lower extremity ultrasound examination can significantly improve the detection of atherosclerosis in adults with diabetes.

To investigate the relationship between non-high density lipoprotein cholesterol (non-HDL-C), low density lipoprotein cholesterin (LDL-C) and cardiovascular risk factors in the residents of Dalian.

Our sample was derived from the REACTION study. The data was collected from August 2011 to December 2011 in Dalian city, up to 10207 subjects. The follow-up data collected from July 2014 to December 2014. The subjects were divided into respective four groups according to the quartiles of non-HDL-C and LDL-C respectively, to compare the cardiovascular risk factors and other clinical parameters between the groups. Spearman correlation analysis, partial correlation analysis and binary Logistic regression model were used to analyze the relationship between non-HDL-C, LDL-C and cardiovascular risk factors, and the developments of cardiovascular risk factors clustering was compared in quartiles with Cox regression.

(1)When comparing cardiovascular risk factors clustering with the non-HDL-C quartile level, there was statistically significant difference(χ²=35.361, P<0.001). When Comparing cardiovascular risk factors clustering with the LDL-C quartile level, there was statistically significant difference(χ²=19.888, P<0.001). (2)According to Spearman partial correlation analysis, adjusting for age, sex and smoking, analysis cardiovascular risk factors clustering was positively and significantly correlated with both non-HDL-C and LDL-C (r=0.092, 0.046, P<0.05). (3)Define the development of cardiovascular risk factors clustering in 2014 as the endpoint with Cox regression analysis. It showed that both non-HDL-C and LDL-C, with age and smoking status into the equation, the differences were statistically significant [non-HDL-C, age and smoking status HR(95%CI):1.248(1.181-1.318),0.988(0.980-0.996),1.616(1.285-2.033);LDL-C,age and smoking status HR(95%CI):1.236(1.159-1.319),0.990(0.982-0.997),1.627(1.293-2.046), all P<0.05].

(1)With the increase of non-HDL-C or LDL-C levels, the prevalence rate of cardiovascular risk factors clustering increases accordingly in the residents of Dalian.(2)Both non-HDL-C and LDL-C are independent risk factors for cardiovascular risk factors clustering.

To evaluate the effect of Clinical Expert Guidance on Short-term Intensive Insulin Therapy for type 2 diabetes mellitus(T2DM)on blood glucose management in hospitalized patients with T2DM.

From November 2017 to December 2018, 320 with T2DM who accepted intensive treatment of basal plus bolus insulin from 30 hospitals participating in the "Guidance" training were selected and divided into the compliance group (206 cases) and the non-compliance group (114 cases). The compliance group followed the "Guidance" for intensive treatment, and the non-compliance group did intensive treatment without following the "Guidance". Finger-tip blood glucose was monitored 7 times per day, insulin dose was adjusted according to the blood glucose. Flash glucose monitoring (FGM) system was started at the Day 1 and lasted for 7 to 14 days. The blood glucose fluctuation and time of blood glucose within target range (TIR) of the two groups were observed and compared by independent sample test, Chi-square test or Fisher exact probability method.

The standard deviation of blood glucose level, postprandial glucose excursion (PPGE), largest amplitude of glycemic excursions (LAGE) and absolute mean daily difference (MODD) in the compliance group were lower than those in the non-compliance group, but there was no statistical differences (P>0.05). The proportions of patients with TIR ≥ 70% were 19% and 17% on the first day, 21% and 22% on the second day, 33% and 26% on the fourth day, and 45% and 36% on the seventh day respectively in the compliance group and the non-compliance group. The proportion of patients with TIR ≥ 70% in the compliance group was higher than that in the non-compliance group, and the trend became more obvious with the extension of treatment time. The blood glucose control rates of the two groups both increased day by day during the treatment, but the control rates and speed of achieving the glucose target in the compliance group were superior than those in the non-compliance group. On the third, fourth, fifth, sixth and seventh day, the blood glucose control rates of the two groups were 14% and 6%, 21% and 10%, 24 and 14%, 36% and 12%, 38% and 22%, respectively. On the 7th day of treatment, the fasting plasma glucose level in the compliance group was lower than non-compliance group, 7.0 mmol/L and 7.7 mmol/L, respectively. After the blood glucose achieved the target, in the compliance group, the proportions of patients whose basal insulin dose accounted for 40% to 60% of the whole day insulin dose decreased day by day, were 93%, 90%, 76%, 60% and 59% on the 3rd, 4th, 5th, 6th and 7th day, respectively, however, it showed an upward trend in the non-compliance group.

The management adhering to the "Guidance" is helpful to improve the blood glucose control, but there is no significant improvement in blood glucose fluctuation.

To study the difference of blood glucose control and perinatal outcome between metformin combined with insulin and insulin alone in patients with pregestational diabetes.

From January 2015 to December 2018, patients with pregestational diabetes were collected in Peking Union Medical College Hospital for routine antenatal examination and delivery. The blood glucose, insulin dosage and perinatal outcome of each group were compared. The differences between the two groups were compared using Student′s t test or Mann-Whitney U test. Categorical variables were compared using Chi-square test.

Eighty patients were enrolled, with 41 in type 1 diabetes mellitus (T1DM) group, 39 in type 2 diabetes mellitus (T2DM) group, 21 in metformin group and 59 in insulin group. The levels of glycosyated hemoglobin A_1c (HbA_1c) and glycated albumin (GA) in T1DM group were higher than those in T2DM group (P<0.05). The insulin dosage in T1DM group was higher than that in T2DM group (P<0.05). There was no significant difference in the perinatal outcome of gestational weeks, cesarean section rate, premature delivery, pregnancy complications, neonatal length, weight, 1 minute Apgar score, low birth weight, macrosomia, neonatal hypoglycemia, other neonatal complications and congenital malformations between the two groups. The HbA_1c and GA before metformin combination were higher than those in insulin-alone group, but there was no significant difference in HbA_1c and GA after metformin combination. The insulin dosage in metformin-insulin group was lower during third trimester (P<0.05). The risk of neonatal hypoglycemia was lower than that in the insulin-alone group (P=0.032).

In pregnant women with T1DM, the dosage of insulin is higher than that in T2DM. Insulin combined with metformin can improve glucose management, significantly reduce insulin dosage and the incidence of neonatal hypoglycemia in pregestational diabetes.

To compare clinical characteristics of impaired glucose regulation (IGR) diagnosed with oral glucose tolerance test (OGTT) and prediabetes (PreDM) with glycated hemoglobin A_1c (HbA_1c).

This was a cross-sectional study. A total of 402 subjects who were high-risk for diabetes from Yanqing District in Beijing underwent a 75 g OGTT and an HbA_1c test during July 2019 to November 2019. The data of height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were collected. Fasting plasma glucose (FPG), 2-hour postload blood glucose (2 h PG), fasting insulin (FINS), 2-hour postload insulin (2 h INS), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were examined. The body mass index (BMI), homeostasis model assessment of β cell function (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index were calculated. According to the 2019 American Diabetes Association criteria, the patients were divided into IGR group and PreDM group. All indicators between two groups were compared using independent samplest test or Mann-Whitney U test. One-way analysis of variance or Kruskal-Wallis H test were used for multiple comparisons. The enumeration data were compared using Chi-squared test.

A total of 397 subjects were included after excluding 5 subjects with hemoglobin<110 g/L. Of which, 161 (40.6%) were IGR and 188 (47.4%) were PreDM. The BMI [(28.7±9.2) vs (26.1±3.7) kg/m², t=-3.335, P<0.05] and Matsuda index [4.64 (3.21, 6.89) vs 4.08 (2.85, 5.95),Z=-2.443, P<0.05] in IGR group were lower than those in PreDM group, and the levels of FPG [(5.7±0.5) vs (5.9±0.6) mmol/L,t=3.611, P<0.01], 2 h PG [(7.4±1.9) vs (8.7±1.6) mmol/L,t=6.757, P<0.01] and 2 h INS [(56.8±45.7) vs (69.3±50.5) mU/L,t=2.418, P<0.05] were higher than those in PreDM group. There were no significant differences in the level of SBP, DBP, FINS, HbA_1c, TG, TC, LDL-C, HDL-C, HOMA-β and HOMA-IR between two groups (all P>0.05). Compared to IGR subgroup with HbA_1c<5.7%, 2 h PG and 2 h INS were lower while level of HbA_1c was higher in PreDM subgroup (all P<0.05). There were no significant differences in the level of BMI, SBP, DBP, FPG, FINS, TG, TC, LDL-C, HDL-C, HOMA-β, HOMA-IR and Matsuda index between two groups (allP>0.05).

IGR and HbA_1c-defined PreDM not only have different hyperglycemic profiles, but also varies in BMI, insulin resistance and β cell function.

To investigate the relationship between serum uric acid (SUA)levels and proinsulin (PI) in subjects with normal glucose metabolism.

A total of 999 adults with normal glucose metabolism confirmed by 75 g oral glucose tolerance test in Haikou City and Wanning City of Hainan Province from April to December 2018 were collected, including 337 males and 662 females with an average age of (44.45±12.97) years. All subjects received questionnaire survey, and their SUA, fasting blood glucose level, fasting insulin level and other laboratory parameters were detected. Fasting PI (FPI) and FPI to insulin ratio (FPI/I) were used to evaluate islet β cell function, and homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess insulin resistance level. According to SUA quartiles, the subjects were divided into four groups: group 1 (SUA<283 μmol/L,n=246), group 2 (283 μmol/L≤SUA<336 μmol/L,n=249), group 3 (336 μmol/L≤SUA<400 μmol/L,n=253) and group 4 (SUA≥400 μmol/L, n=251). The clinical indexes between different groups were compared with analysis of variance and rank sum test. Additionally, multiple linear regression analysis was performed to investigate the effect of SUA on islet β cell function.

A total of 190 people were diagnosed with hyperuricemia, including 159 males and 31 females. Theβ cell function indexes in patients with higher SUA level (group 4), including FPI and FPI/I, were higher than those in patients with lower SUA level (group 1) [13.43 (13.34) vs 9.26 (7.96) pmol/L; 0.25 (0.20) vs 0.19 (0.20), both P<0.01]. Multiple linear regression analysis showed that the plasma SUA level was linearly related to FPI level even after adjusting for age, gender, body mass index, waist circumference, fasting plasma glucose, fasting insulin and HOMA-IR (β=0.013, P<0.01). For every 100 μmol/L increase in SUA, FPI increased by 1.3 pmol/L on average in all subjects. However, when analyzed in gender-specific subgroups, the SUA level was still linearly correlated with FPI but not with FPI/I after adjustment for potential confounding factors (maleβ=0.014, P<0.05; femaleβ=0.010, P<0.01).

There is a positive linear correlation between SUA and FPI in patients with normal glucose metabolism. We should pay attention to the early changes of islet β cell function in hyperuricemia patients

To evaluate the remission rate of metabolic syndrome (MS) 3 years after Roux-en-Y gastric bypass (RYGB) and the predictive factors associated with MS remission in Chinese patients with obesity and MS.

This study was a retrospective cohort study and included 148 obese patients with MS who were treated with RYGB in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital from July 2011 to April 2016. All patients were followed up for 3 years after surgery. The medical history and physical examination data, including duration of diseases, medication history, family history of diabetes, blood pressure, waist circumference, etc. were collected. Fasting blood glucose, glycated hemoglobin A_1c, blood lipid profile, C-reactive protein (CRP) and other indicators were detected. Body mass index (BMI) and percentages of total weight loss (TWL) were calculated. According to whether or not their MS were remission 3 years after metabolic surgery, all patients were divided into MS remission group (n=85) and non-remission group (n=34). The t test and χ² test were used to compare the clinical data between the two groups, and a multivariate logistic regression model was established to analyze the related factors affecting MS remission.

A total of 119 patients (80.4%) with an average age of (48.3±11.4) years old were followed up for 3 years. Among these patients, 70 cases (58.8%) were female. The BMI was (31.6±3.5) kg/m² before surgery but was decreased to (25.3±3.3) kg/m² 3 years after surgery. The prevalence of MS decreased from 100% (119/119) before surgery to 28.6% (34/119) three years after RYGB surgery, and the differences were statistically significant (χ²=132.2, P<0.01). Percentage of TWL in the MS remission group was higher than that of the non-remission group, the differences were statistically significant [(20.9±6.9)% vs (17.4±6.5)%, t=2.626,P=0.011]. Logistics multiple regression analysis revealed that preoperative CRP [odds ratio (OR)=0.79, 95% confidence interval (CI): 0.68-0.92, P<0.01] and percentage of TWL (OR=1.09, 95%CI: 1.00-1.19, P=0.047) were independent influencing factors of MS remission at 3 years after metabolic surgery.

RYGB can improve MS in Chinese obese patients. The higher the percentage of TWL, the lower the preoperative CRP, and the greater the possibility of remission of MS after RYGB. Mid-term MS remission after RYGB may be associated with weight loss and improvement of chronic inflammation.

To explore the feasibility and utility of quantitative proteomics tandem mass tag (TMT) in screening antimicrobial peptides from diabetic foot skin.

During April 2017 to December 2018, 3 samples from the skin around the ulcer of the lower extremity in patients with diabetic foot who underwent debridement, and another 3 from the skin around the ulcer of the lower extremity in non-diabetic patients who received other operations in Zhongda Hospital, Southeast University, were collected. TMT was used to analyze the proteomics of these samples, and the significantly changed proteins were screened. The biological functions of the identified differential proteins were interpreted based on UniProt-GOA database. Using the identified proteins as the background, Fisher exact test was used to evaluate the function of differentially expressed proteins. The magnitude of the enrichment of functional domains of differentially expressed proteins was analyzed using InterPro database.

A total of 133 differentially expressed proteins were identified, of which 101 and 32 were up-regulated and down-regulated, respectively. Gene ontology (GO) enrichment analysis showed that the most significant enrichment process in protein biology was the defense process against bacteria, followed by the humoral response process against bacteria. A total of 19 proteins involved in the defense response process to bacteria, of which 18 proteins were up-regulated and 1 protein was down-regulated. Eight proteins were up-regulated more than four-fold, which included Lysozyme C, neutrophil elastase, bactericidal permeability increasing protein, lactoferrin, membrane-associated phospholipase A2, peptidoglycan recognition protein 1, immune globulin J chain, and protein S100-A12. A total of 8 proteins were involved in the process of antimicrobial humoral response, of which 7 proteins overlapped with proteins involved in the defense response to bacteria. Protein interaction analysis showed that the differentially expressed antimicrobial proteins formed a complex regulatory network with 14 nodes and 34 edges, the average node degree was 4.86, and the clustering coefficient was 0.652.

The TMT labelled proteomics suggested that proteins, such as lysozyme C, neutrophil Elastase, bactericidal permeability increasing protein, lactoferrin, membrane-associated phospholipase A2, peptidoglycan recognition protein 1, immune globulin j-chain and protein S100-A12, which are involved in the defense and humoral immune responses against bacteria, hold promise as the new target for the treatment of diabetic foot infection.

To explore the effect of gut microbiota transplantation from diabetic mice on the renal pathologic structure and microalbuminuria in germ-free mice.

Leptin-deficient ob/ob male mice (n=20) were chosen as animal model of diabetes mellitus. Wild-type male C57BL/6 mice (n=10) were chosen as control group. The differences in bacterial species and diversity between diabetes mellitus and control group were analyzed through high-throughput sequencing technology and bioinformatics approaches. Thirty germ-free mice were selected and randomly divided into three groups: normal group (GF-CON), control group (GF-CON) and diabetic group (GF-DM), which was gavaged with equal volume phosphate buffer solution (absence of feces), phosphate buffer solution (including feces of wild-type mice in control group) and phosphate buffer solution (including feces of mice in ob group) at a single dose of 0.2 ml per day, respectively. Pathological changes in the kidney of germ-free mice were assessed using hematoxylin-eosin staining and concentrations of urine microalbumin were measured. The t test was used to compare the data between two groups. Statistical significance was performed by one-way ANOVA, followed by LSD-t test for pairwise comparison among multi-groups.

Compared with control group, body weight and blood glucose concentration were significantly increased in diabetic mice (both P<0.01). A decrease in both Shannon′s and Simpson′s diversity indexes of gut microbiota was observed in diabetic mice (3.66±0.16 vs 4.40±0.13, 0.028±0.002 vs 0.046±0.005, respectively,t=3.19, 2.57, both P<0.05). The abundances of Firmicutes were significantly decreased, and that of Bacteroidetes and Proteobacteria were significantly increased in the diabetic mice compared with that of control group, respectively (P<0.01 orP<0.05). Although the abundances of Actinobacteria increased, there was no statistical difference between the two groups (P>0.05). The colonization of gut microbiota from diabetic mice induced glomerular cell proliferation and renal tubule atrophy in germ-free mice at week eight. The concentration of urine microalbumin was also significantly increased compared with control group after four weeks and eight weeks, respectively [(8.26±2.93) vs (2.19±0.85) μmol/L, (11.04±3.32) vs (3.13±0.74) μmol/L,t=2.80, 3.65, both P<0.01].

There are differences in the gut microbiota composition between diabetes mellitus and control group. After gut microbiota transplantation from diabetic mice, pathological changes in kidney were observed, and urinary microalbumin increased in germ-free mice.

It is hoped that by sorting out the health economic evaluation models of diabetic peripheral neuropathy (DPN) in previous research literatures, analyzing the characteristics of model architectures in different studies, comparing and sorting out different model structures and parameter values, and constructing an economic evaluation model framework suitable for clinical diagnosis and treatment environment in China. Markov model is a widely applicable model framework in the evaluation of diabetes DPN health economics. Based on the diagnosis and treatment path in China, five state Markov models can be constructed for future reference of diabetes DPN health economics research.

Diabetic cardiovascular complications are the leading cause of death in type 2 diabetes. sodium-glucose cotransporter-2 (SGLT2) inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubules of the kidney, leading to osmotic diuresis and lowering blood glucose. Recent clinical studies have shown that SGLT2 inhibitors can reduce major cardiac adverse events in diabetic patients with high-risk cardiovascular risk, but the mechanism has not been fully understood. In this paper, the mechanism of cardiovascular protective effect of SGLT2 inhibitors was expounded from the aspects of heart failure, hypertension, abdominal aortic aneurysm, coronary atherosclerotic heart disease and other macrovascular diseases, so as to have a deeper understanding of the cardiovascular protective mechanism of SGLT2 inhibitors.

Diabetic nephropathy (DKD) is a common and serious microvascular complication of diabetes mellitus, and it is also the main cause of end-stage renal disease. At present, there is still a lack of sensitive and reliable early markers to predict the occurrence and development of DKD. Although renal biopsy is the "gold standard", it is invasive and risky, so it is difficult to make a large-scale general survey. Retinal blood vessels are common damage targets in the early stage of diabetes mellitus, and they are also the only living blood vessels in human vascular system that can be directly visualized. Changes in their morphology, structure or function can directly or indirectly reflect DKD. Especially in recent years, the development of optical coherence tomography angiography, a non-invasive technique, has provided help for the quantification of retinal microvascular disease.