Volume 11 · Issue 12 · 2019

The prevalence of cardiovascular complications in diabetes mellitus is high, which seriously affects the prognosis of patients. With the successive publication of cardiovascular outcome test results of hypoglycemic drugs, the cardiovascular safety of hypoglycemic drugs has attracted more and more attention of relevant scholars in basic and clinical fields. This paper reviews the cardiovascular benefits of traditional and new hypoglycemic drugs, and evaluates the results of cardiovascular outcome trials and real-world studies of these drugs.

To investigate the effect and mechanism of liraglutide on ectopic fat deposition in rats with diabetic nephropathies (DN).

Forty male SD rats were randomly divided into three groups: normal control rats group (n=10), DN vehicle control rats group (n=15) and DN rats with liraglutide group (n=15). DN rats received subcutaneous injection of liraglutide (0.4 mg·kg^-1·d^-1) for 12 weeks. Body weight, 24 h urine volume, 24 h total urine protein, serum insulin level, blood glucose, serum triglyceride (TG), total cholesterol (TC), and other biochemical index were detected after 12 week treatment of liraglutide. The histopathological changes of rat kidney were evaluated by periodic acid-schiff staining. The protein expression, distribution of sterol regulatory element binding protein and adipose differentiation-related protein in rat kidney were detected with immunohistochemistry. Renal tissue adenosine monophosphate activated protein kinase (AMPK), sterol regulatory element binding protein 1 (SREBP-1), adipose differentiation related protein (ADRP), fatty acid synthase (FAS) and p-AMPK phosphorylation levels protein expression in rats kidney were examined using western blot. One-way ANOVA was used to compare groups, pairwise comparison was tested by the least significant difference method.

Compared to normal control group, the blood glucose, 24 h urine volume, and 24 h total urinary protein levels were increased in the DN vehicle control group (t=8.630-28.251, all P<0.01). When treated with liraglutide for 12 weeks, the total urine protein content of the DN vehicle control rats group was significantly higher than that of the diabetic rats before modeling [(20.3±10.6) vs (5.9±2.0) g/24 h, t=3.965, P<0.01]. Glomerular mesangial cell proliferation and matrix expansion, serum TG and TC was significantly increased (t=3.616, 2.363, all P<0.05) . SREBP-1 and ADRP proteins were mainly distributed in tubular (t=7.588, 6.160, all P<0.01) , and proteins expression of SREBP-1, FAS and ADRP protein in kidney tissue increased significantly, while AMPK phosphorylation levels in kidney tissue decreased (t=6.122,8.78,11.16, -12.78, all P<0.01). Compared to DN vehicle control group, the body weight of DN rats decreased significantly after 12 weeks of treatment with liraglutide, serum TG and TC decreased significantly (t=-3.338, -2.944, -2.390, all P<0.05). SREBP-1, FAS, ADRP protein expression in rats kidney was significantly decreased, while the phosphorylation level of AMPK in renal tissue was increased (t=-2.833, -4.228, -11.850, 7.653, all P<0.05).

Liraglutide inhibits renal ectopic fat deposition in rats with DN, which may be related to the increase of AMPK phosphorylation activity, inhibition of SREBP-1 transcriptional activity, reduction of FAS expression and subsequent inhibition of fatty acid synthesis pathway by liraglutide.

To analyze the pathogen, drug resistance and related factors of diabetic foot infection (DFI) in hospitalized patients.

A total of 574 patients with diabetic foot (DF) who were hospitalized in the Department of Endocrinology from January 2014 to December 2018 were studied. The distribution of pathogenic bacteria, drug sensitivity and related factors were collected. Patients were divided into group A or group B based on test result of foot tissue culture, and the related factors were analyzed. SPSS 22.0 software was used for statistics analysis. χ ² test was used for categorical data between groups, t test was used for numerical data, and Logistic regression analysis was used for multivariable analysis.

698 strains of pathogenic bacteria were isolated from 574 DF patients. The first three were 166 strains of staphylococcus aureus (23.8%), 54 strains of escherichia coli (7.7%) and 50 strains of enterobacter cloacae (7.2%). Wagner grade 3-5 DFI was dominated by gram-negative bacteria, which accounted for 53.3%, 54.8% and 71.4% of total pathogenic bacteria respectively. Wagner grade 1-2 was dominated by gram-positive bacteria, accounting for 62.7% and 53.8%. Gram negative bacteria (except for Pseudomonas aeruginosa and Acinetobacter baumannii) were more sensitive to meropenem (sensitivity≥98%), imipenem (≥92.6%), piperacillin/tazobactam (≥85.3%); gram positive bacteria were more sensitive to quinolones (sensitivity ≥80%); vancomycin, linezolidine and tegacyclinwere the most sensitive, sensitivity 100%. Logistic regression analysis showed that the length of diabetic foot disease (OR=3.40, 95%CI:1.87-6.20), combined with peripheral vascular lesions (OR=1.42, 95%CI:1.17-1.71), peripheral neuropathy (OR=1.23, 95%CI:2.28-19.69), white blood cells high (OR=4.45, 95%CI: 1.36-13.25), high glycated hemoglobin (OR=5.810,95%CI:2.93-11.54), low density lipoprotein high (OR=1.54, 95%CI: 1.10-2.15) was a major risk factor for DFI.

The treatment of DFI should be determined based on clinical characteristics of patients and empirical selection of sensitive antibiotics with further adjustment according to drug sensitivity test.

To evaluate the static balance function in patients with impaired glucose regulation.

Twenty-nine patients [13 males and 16 females, mean age (49.69±6.13) years] with impaired glucose regulation (IGR group) were recruited from Fuxing Hospital of Capital Medical University between July 2016 and August 2017, and 24 healthy controls [5 males and 19 females, (46.37±7.19) years, Con group] were recruited in the same period. General baseline data and endocrine-related test results were collected. Static balancing apparatus was used to evaluate the balance function of the subjects. The evaluation indexes include the unit area statokinesigram length (UAL), total length of the track, maximum amplitudes, the surface of statokinesigram area (SSKG) and Romberg quotient. Two independent samplest test was used to compare the mean of the two groups with normal distribution, Mann-Whitney U test was used to compare the data with non-normal distribution, and χ ² test was used to compare the rates.

(1) When standing on the hard platform with eyes opened, there was no statistically significant differences in SSKG, total length of the track, maximum amplitudes and UAL between IGR group and Con group (t=1.302-1.583, P>0.05); (2) When standing on the hard platform with eyes closed, SSKG, total length of the track, maximum amplitudes and Romberg quotient were all higher in IGR group than those in Con group [(829.22±299.48) vs (337.23±161.69) mm; (1 035.17±354.77) vs (835.75±299.48) mm; (55.38±21.89) vs (39.71±9.22) mm; (1.83±0.98) vs (1.25±0.58)%, respectively], and the UAL in IGR group was lower than that in Con group [(1.79±0.87) vs (2.76±1.22) mm, t=-3.332, P=0.002].

When eyes open, there is no difference in the static balance function between IGR group and control group. under the condition of visual deprivation, the static balance function in IGR group is lower than that in con group; the increase of Romberg quotient indicates that the maintenance of standing static balance function in IGR patients depends more on visual compensation.

To investigate the prevalence of dyslipidemia and diabetes mellitus in adult residents of Jiangxi Province, and to explore the correlation between dyslipidemia and diabetes mellitus.

A multi-stage stratified random sampling method was adopted to conduct cross-sectional survey of 5 040 residents over 18 years old in 14 urban and rural community committees in Jiangxi Province from March to July 2018, including questionnaire, physical examination, oral glucose tolerance test and biochemical indicators etc. SAS software was used for statistical analysis and Chi-square test was used for comparing the differences and tendency test. Logistic regression model was used for multiple-factor analysis.

The standardized prevalence of dyslipidemia in adults and diabetes mellitus was 28.79% and 11.68% respectively in Jiangxi Province. The prevalence of dyslipidemia in adult females increased with age (P<0.01), while that in males decreased with age (P<0.01). The prevalence of diabetes mellitus increased with the increase of body mass index (P<0.01). Mixed dyslipidemia had a greater impact on blood glucose metabolism than single dyslipidemia (P<0.05). Logistic regression analysis showed that dyslipidemia, high triglyceride, high low density lipoprotein cholesterol were independent risk factors for diabetes mellitus in adults in Jiangxi Province, with OR values of 1.395, 1.116 and 1.331, respectively (all P<0.05). The incidence of adult diabetes mellitus in Jiangxi Province was not related to the levels of total cholesterol and high density lipoprotein cholesterol (P>0.05).

Dyslipidemia is closely related to diabetes.People with obesity, overweight or mixed dyslipidemia are at higher risk of diabetes. Prevention and control work should be differentiated according to crowed characteristics.

To investigate the relationship between serum adipose differentiation-related protein (ADRP) and nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM).

This study enrolled 102 patients with T2DM hospitalized in the Department of Endocrinology, the First Affiliated Hospital of Soochow University, between January and October in 2016. The patients were divided into T2DM+NAFLD group (n=52) and T2DM+non-NAFLD group (n=50) according to the presence of NAFLD. In addition, healthy individuals were selected as control group (NC, n=40). The general clinical data were collected. Serum ADRP concentrations were measured with ELISA. Routine metabolic parameters and liver enzymes were also collected. Insulin resistance index was calculated by homeostasis model assessment of insulin resistance (HOMA-IR). Data were analyzed using Chi-Square Test, one-way ANOVA, SNK test, multivariate linear regression analysis and binary logistic regression analysis.

Serum ADRP levels in NC group, T2DM+Non-NAFLD group and T2DM+NAFLD group showed an increasing trend [ (2.98±0.42) , (3.68±0.56) , (4.85±0.45) μg/L, all P<0.05]. The between-group differences had statistical significance (P<0.01). Multivariate linear regression analysis showed that ADRP was independently correlated with age, waist circumference (WC), glycosylated hemoglobin (HbA_1c), HOMA-IR and triglyceride (TG) (β=0.007,0.016,0.109,0.235,0.268, allP<0.05). Binary Logistic regression analysis showed that ADRP, WC and TG were the independently risk factors for NAFLD with T2DM (OR= 5.916, 3.500, 3.513, all P<0.05).

Increased serum ADRP level acts as an independent risk factor for NAFLD with T2DM. The ADRP level is closely related to age, obesity, insulin resistance, hyperglycemia and hyperlipemia. ADRP may play a role in the pathogenesis and development of diabetes and NAFLD.

To investigate the clinical characteristics, biochemical parameters, radiographic features and prognosis of malignant insulinomawith liver metastasis.

We retrospectively analyzed the clinical data of 4 cases of malignant insulinomaswith liver metastasis recruited in Peking Union Medical College Hospital from December 2016 to December 2018. Related literature were reviewed in this article.

All the 4 cases manifested as Whipple triad with hypoglycemic symptoms gradually aggravated. They all met the criteria for the typical hyperinsulinemic hypoglycemia. Three patients had liver metastasis at the time of diagnosis. Qualitative diagnosis indicated that the ratio of fasting proinsulin to insulin was increased. All 4 patients undertook various radiographic examination. The sensitivity of pancreatic enhanced magnetic resonance imaging (MRI) was the highest in diagnosing primary pancreatic tumor and liver metastases (4/4). Abdominal ultrasound was not sensitive to primary pancreatic tumor (1/4), but sensitive to liver metastases (3/4). All 4 patients underwent insulinoma resection, of which 3 received hepatic metastases resection. Postoperative pathology finding was consistent with liver metastasis of neuroendocrine tumors. Ki-67 index was 1%-15%. Tumor grade was G1 in 2 patients, and G2 in the other 2 patients. Taken together the findings in the literature, it suggested that the increase of proinsulin/insulin ratio is of great significance in the diagnosis of malignant insulinoma. In the treatment of malignant insulinoma with hepatic metastasis, surgical resection of primary tumor and hepatic metastases yielded relative optimal prognosis.

The increase of proinsulin/insulin ratio is of great clinical significance in the diagnosis of malignant insulinoma. Enhanced pancreatic MRI is the most sensitive for both primary tumor and liver metastases. Surgical removal of primary and metastatic lesions is the most effective treatment to improve prognosis of malignant insulinoma with liver metastasis.

This study aimed to analyze the association of inflammasome-associated gene AIM2 polymorphism with classical type 1 diabetes mellitus (T1DM) in Chinese Han population. Two single nucleotide polymorphism sites rs2276405 and rs2793845 of the AIM2 gene were genotyped by mass spectrometry in 510 Chinese Han classical T1DM patients and 531 healthy controls. Chi-square test and Logistic regression were used to compare the frequency of alleles and genotypes in patients with T1DM with controls and the association with T1DM under different genetic models. Kruskal-WallisHThe relationship between AIM2 gene polymorphism and various clinical characteristics was analyzed. The results showed that the rs2276405 locus of AIM2 gene was significantly associated with T1DM. The rs2276405 polymorphism was associated with T1DM in both dominant and additive genetic models. The polymorphism of AIM2 gene was not associated with clinical characteristics. These results suggest that the rs2276405 locus of our AIM2 gene is significantly associated with the classical T1DM in Chinese Han population, and the secondary allele is the protective allele.

Type 1 diabetes is a chronic disease in which autoimmune reactions cause the destruction of pancreatic islet beta cells. Cord blood or umbilical cord contains abundant stem cells. Compared with other stem cells, cord blood stem cells have the advantages of abundant source, convenient collection, low immunogenicity, stronger proliferation and differentiation ability and low infection probability. Cord blood stem cells can be differentiated into insulin-secreting cells, and have immune regulatory effects, which can fundamentally play a therapeutic role in the pathogenesis of type 1 diabetes. They are new methods and research hotspots in the field of treatment of type 1 diabetes.

With the change of people's diet structure and lifestyle, the incidence of obesity and type 2 diabetes mellitus (T2DM) is increasing year by year. T2DM is a polygenic hereditary complex disease formed by the combination of genetic and environmental factors, which is characterized by insulin resistance and islet β cell dysfunction. In recent years, ectopic lipid deposition, especially lipotoxic substances caused by pancreatic fat deposition, has become a hot topic of research on the etiology of T2DM. This paper reviews the epidemiology, diagnostic methods, mechanism of promoting the pathogenesis of T2DM and the correlation with T2DM, in order to improve the understanding of pancreatic fat deposition, and provide scientific basis for exploring the pathogenesis of T2DM and delaying the disease of T2DM.

With the rise of Internet telemedicine services, applications (APPs) provide powerful tools for integrated diabetes management. However, at present, there is a lack of a perfect system for objectively evaluating the quality of diabetes management apps. The newly proposed mobile APP scoring scale is not comprehensive enough, and there is a lack of quality evaluation for specific disease-related content. Clinical studies have shown that the effectiveness of APP in improving patients' blood sugar control and self-management ability is also inconsistent. In the future, it is necessary to build a complete APP quality evaluation system, and at the same time, more high-quality clinical studies are needed to verify the effectiveness of diabetes management APP, so as to promote the application and continuous improvement of APP in the field of comprehensive diabetes management.

Continuous glucose monitoring is becoming more and more popular in clinical practice. In recent years, glucose time within the target range (TIR) has attracted more and more attention. It can more fully reflect the blood glucose control level of patients, is an important supplement to glycated hemoglobin, and has a significant correlation with diabetic retinopathy and microalbuminuria. In order to standardize the clinical application of TIR, the Diabetes Advanced Technology and Treatment Conference has formed an international consensus on the clinical application of TIR, and made specific recommendations on TIR measurement methods, technical requirements, and target setting for different patients. TIR will become one of the important indicators of blood glucose control and comprehensive diabetes management.

Since 2008, the U.S. Food and Drug Administration has required cardiovascular outcome study (CVOT) results for new hypoglycemic drugs. Based on the concept of evidence-based medicine, CVOT, as a randomized controlled study (RCT), provides evidence of the first level of evidence, which is considered as the gold standard for testing efficacy. However, at the same time, RCT has the defect of external authenticity limitation. Real-world research (RWS) can bridge the gap between RCT and clinical practice, so it has been paid more and more attention in recent years. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new class of hypoglycemic drugs, and their CVOT and RWS studies have been reported. This paper will take RCT and RWS reported by SGLT2i as examples, compare and analyze the differences in research design and interpretation of results between the two studies, and explore the relationship between them and the application value of clinical evidence.