Volume 06 · Issue 05 · 2014

Insulin is the only hormone in the body that lowers blood sugar. For diabetic patients with defective insulin secretion or action, exogenous insulin plays an important role in blood glucose control and complication prevention. With the continuous development of insulin preparations and the increasing scope of clinical application, the clinical benefits of insulin therapy are accompanied by the emergence of therapeutic risks. The selection of insulin use timing, the determination of dosage form and dose, and the related problems brought by insulin use are attracting people's attention.

On March 6, 2014, the Chinese Diabetes Journal "Yikai Cup" Diabetes Physician Salon was successfully held in Beijing. This salon was hosted by Professor Pan Changyu, a senior consultant of Chinese Diabetes Journal and a famous endocrinologist, and Director Yang Ying of the editorial department of Chinese Diabetes Journal. The case discussion process was hosted by Professor Yu Miao of Peking Union Medical College Hospital and Professor Yang Guoqing of PLA General Hospital respectively. A total of nearly 60 young doctors from the field of diabetes in Beijing attended this salon. The doctors in the salon spoke enthusiastically, and the atmosphere was warm. Through this way of brainstorming and knowledge stirring, everyone's clinical diagnosis and treatment thinking was expanded. The salon continues to be co-organized by Changzhou Qianhong Pharmaceutical Co., Ltd.

In the spring of March, Beijing, the capital, has a little warmth. On March 15th, 2014, the "Xingzhi Lecture Hall" activity jointly sponsored by the Editorial Committee of Chinese Diabetes Journal and the Youth Committee of Diabetes Branch of Chinese Medical Association and supported by AstraZeneca officially kicked off.

Diabetes is currently a chronic disease with high prevalence, which seriously endangers human health. Epidemiological studies show about 285 million (6.4%) adult patients worldwide in 2010 and 439 million (7.7%) in 2030^[1]。 Among them, there are 92.4 million (9.7%) diabetic patients over the age of 20 in my country, which has become the country with the largest number of diabetic patients in the world, among which type 2 diabetes (T2DM) patients account for the vast majority^[2]。 The study found that the islet cell function in patients with T2DM was only 50% at the onset of the disease, and it decreased progressively with the prolongation of diabetes^[3](Figure 1)。

In 1921, insulin was first used in the clinical treatment of type 1 diabetes mellitus (T1DM) in Toronto Hospital, Canada. Since then, T1DM has changed from acute fatal disease to chronic disease. In the past century, diabetic insulin treatment has undergone tremendous changes, from bottled insulin syringe injection, injection pen injection, needle-free injection to continuous subcutaneous infusion pump. With the continuous innovation of technology, milestones have emerged one by one. Despite this, multiple exogenous insulin injections are still not comparable to the physiological insulin secretion pattern of normal people, especially for fragile diabetes with a long course of disease and complete loss of pancreatic islet function. Even if insulin injections are basically plus three meals, it is still difficult to avoid the huge fluctuation of blood sugar^[1,2]。 The use of a continuous subcutaneous infusion pump can provide a more stable basal insulin, but it still cannot achieve on-demand infusion according to blood glucose levels. Therefore, the need for clinical treatment has driven further exploration of insulin infusion modalities and technologies that are closer to physiological.

To assess the clinical safety and efficacy of multi-parameter bolus advisor in insulin pump therapy and explore clinical application value of the multi-parameter bolus advisor.

A total of 158 diabetic patients from endocrine departments of 10 tertiary comprehensive hospitals were randomly (2∶1∶1) assigned to three groups from May 2012 to July 2013, including therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) with multi-parameter bolus advisor (BA-CSII group), common CSII system (CO-CSII group), and multiple daily injection (MDI group). The insulin dosage, blood glucose controlling, and incidence of hyperglycemia or hypoglycemia episodes during the hospitalization were compared and analyzed by chi-square test, Mann-Whitney U test and Kruskal-Wallis H test among the three groups.

After treatment, the ratio of postprandial blood glucose reaching the individualized target in BA-CSII group was significantly higher than CO-CSII group (78.1% vs 52.3%, χ ²=7.955, P<0.05) and MDI group (78.1% vs 50.0%, χ²=8.375, P<0.05), and postprandial blood glucose level of BA-CSII group was remarkably lower than CO-CSII group ((7.8±2.0)vs (9.1±2.8)mmol/L,Z=-2.301, P<0.05) and MDI group ((7.8±2.0)vs (9.1±2.2)mmol/L,Z=-2.920, P<0.05). The incidence of hypoglycemia (blood glucose≤3.9 mmol/L) and the per capita frequency of hyperglycemia (blood glucose≥10 mmol/L) in BA-CSII group were lower than those in CO-CSII group and MDI group, but there were no significant differences observed (P>0.05). Moreover, during the hospitalization, the average daily insulin dosage of BA-CSII group was lower than that in MDI group ((44.4±17.0)vs (55.7±27.3) U,P>0.05), and that of CO-CSII group ((39.3±11.6)vs (55.7±27.3) U,Z=-2.690, P<0.05) was significantly lower than that in MDI group, too. Compared with that of the hospital admission day, the insulin dosage of BA-CSII group decreased more than CO-CSII group on discharge day, whereas the insulin dosage of MDI group increased, and no obvious contrasts were found among three groups (allP>0.05).

The application of multi-parameter bolus advisor can improve postprandial glucose control in intensively treated diabetics, with less hypoglycemia risk and lower insulin dosage. Accordingly, automated bolus advisor was proven to be a safe and effective feature for insulin-pump system.

To explore the changes in islet β-cell function during continuous subcutaneous insulin infusion (CSII) in type 2 diabetic patients and to observe the possible relationship between these changes and the improvement of β-cell function after CSII.

A total of 36 type 2 diabetic patients were enrolled from January 15, 2013 to March 20, 2013. After hospitalized, fasting blood was collected for basic biochemical tests, lipid profile, HbA1c, and arginine stimulated C-peptide(CP) test was performed. Then the patients were recruited to 9-13 days CSII therapy. The arginine stimulated CP test was repeated during and after CSII. The decreasing amplitudes of fasting C peptide(FCP) and the increment of CP(indicated by ΔFCP%, ΔCPi%) after arginine during CSII were calculated, in which the correlations between the two indexes and the CP levels after CSII were observed. Data analysis were performed using SPSS 16.0.

After the brief course of CSII therapy, fasting plasma glucose level fell from (13.6±3.7) to (6.6±1.5) mmol/L(t=9.374, P<0.05), and the level of FCP increased significantly ((0.71±0.30) vs (0.62±0.29) pmol/L,t=2.854, P<0.05). During CSII, both FCP level and the increment of CP (CPi) after stimulating of arginine evidently decreased, compared with those before and after CSII (FCP: at target (0.25±0.20) pmol/L vs before treatment (0.62±0.29) pmol/L, after treatment (0.71±0.30) pmol/L,t=-9.153, -11.021, P<0.05; CPi: at target(0.37±0.30) pmol/L vs before treatment(0.58±0.41) pmol/L, after treatment(0.52±0.30) pmol/L,t=-6.201, -4.856, P<0.05). In the multiple linear regression analysis, after the adjustment for age, blood glucose, duration, BMI and creatinine clearance rate, ΔFCP% and ΔCPi% were independently related to CPi after CSII treatment (standardized β values: -0.329, -0.334,P<0.05).

CSII can provide a useful therapeutic strategy for speedy, stable glycemic control and improving the retained β-cell function in type 2 diabetes patients. During CSII, the β-cell function is suppressed significantly, which can recover rapidly after the end of CSII and the decreasing amplitude of β-cell function is negatively correlated with the improvement of that after CSII.

To compare the clinical efficacy of biphasic insulin aspart50 and biphasic human insulin50 in the treatment of type 2 diabetic patients.

Selecting the type 2 diabetic clinical in-patients of 50 cases in Department of Endocrinology, Tinghu District People's Hospital, Yancheng, Jiangsu Province from February of 2012 to February of 2013 for study subjects, which all meet the criterion of WHO diabetes mellitus diagnosis in 1999. Fifty patients were divided into two groups randomly. The patients were treated with Biphasic Insulin Aspart50 in group A (n=25), and Biphasic Human Insulin50 in group B (n=25). Fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2 hPG), HbA1c, BMI, dosage of insulin, and incidence of hypoglycemia were observed at the baseline and the end of 2 week-treatment and 12 week-treatment. The analysis was done using SPSS 17.0 statistical software and the measurement data was compared using group t-test and the count data was compared by χ ² test.

After 2 week-treatment, the levels of FPG and 2 hPG decreased significantly from baseline in the two groups, the decrease in group A of blood glucose after breakfast, lunch and dinner was significantly more than that in group B. The differences have statistical significance (t=3.342, 3.392 and 2.504 respectively, P<0.05 all above). But the decrease of pre-dinner and pre-sleep in group B was significantly more than that in group A. The differences have statistical significance (t=2.532, 3.066, respectively, P<0.05 all above). After treatment for 12 weeks, the decrease of HbA1c, 2 hPG and insulin dosage in group A was significantly more than that in group B (P<0.05). HbA1c in group A falled from (10.6 ± 1.9)% before treatment to (6.7 ± 0.5)% after treatment and HbA1c in group B falled from (10.5±1.5)% before treatment to (7.1±0.6)% after treatment .The differences between two groups have statistical significance (t=3.808, P<0.05). 2 hPG in group A falled from (21±5)mmol/L before treatment to (7.1±0.9)mmol/L after treatment and 2 hPG in group B falled from (21±5)mmol/L before treatment to (8.4±1.6)mmol/L after treatment. The differences have statistical significance (t=3.331, P<0.05). No statistical differences were observed in FBG (P>0.05). Insulin dosage significantly decreased in two groups after 12 week-treatment. Some patients stopped using insulin. In group A, insulin dosage falled from (50 ± 13) U/d after 2 week-treatmet to (32 ± 12) U/d after 12 week-treatment and in group B , insulin dosage falled from (59±10) U/d after 2 week-treatmet to (39±6)U/d after 12-week treatment. The differences have statistical significance (t=3.399, P<0.05). Before treatment body weight has no statistical difference between two groups, and the body weight has no statistical difference between before and after 12 week-treatment (P>0.05 all above). The gain of weight in group B was more than that in group A (t=2.319, P<0.05). No severe hypoglucemia happened in two groups. The rate of hypoglycemia in group B was significantly more than that in group A (χ²=4.500, P<0.05).

Biphasic Insulin Aspart50 is superior to Biphasic Human Insulin50 in the reduction of HbA1c, 2 hPG and the dosage of insulin and dose not increase hypoglycemic episodes and weight gaining significantly.

To assess the relations between glycosylated hemoglobin A1c(HbA1c) and β-cell function as measured by indices derived from oral glucose tolerance test (OGTT) in Chinese subjects.

A total of 913 subjects, who underwent 75 g OGTT for evaluation of glucose intolerance from June 2010 to February 2013, were included. According to OGTT, the enrolled subjects were divided into the following three groups: normal glucose tolerance (NGT, n=205), impaired glucose regulation (IGR, n=328), and type 2 diabetes mellitus (T2DM, n=380). Meanwhile, the subjects were also divided into three groups according to HbA1c levels: HbA1c <5.7%( n=277), 5.7%≤HbA1c≤6.4%(n=391), and HbA1c>6.4% (n=245). Insulin sensitivity was measured by Matsuda insulin sensitivity index (ISI_M) and 1/homeostasis model assessment of insulin resistance (1/HOMA-IR). β-cell function adjusted by insulin sensitivity was assessed from disposition index (DI) at early-phase DI ₃₀ and total DI₁₂₀. ANOVA, Chi-Square test and general linear model were used for data analysis.

Compared with the HbA1c <5.7% group, the DI ₃₀ , DI₁₂₀, ISI_M, and 1/HOMA-IR were decreased by -39%, -33%, -13%, and -14%, respectively, in the 5.7%≤HbA1c≤6.4% group, and -68%, -66%, -21%, and -32%, respectively, in the HbA1c>6.4% group (F=12.765-317.316, all P<0.05). In NGT group, DI₃₀ and DI₁₂₀ decreased in subjects with elevated HbA1c; in HbA1c<5.7% group, DI₃₀ and DI₁₂₀ declined as glucose increased.

Both impairment of β-cell function and insulin sensitivity contributes to the deterioration of HbA1c in Chinese population. A combination of HbA1c and OGTT is effective in screening for subjects with β-cell dysfunction.

To evaluate the degree of balance in type 2 diabetic patients with long duration(>10 years) aged 65 years or above and to analyze its related risk factors.

A total of 97 diabetic outpatients with a duration over 10 years aged 65 years or above(DM group) and 59 healthy people aged over 65 years (control group)were enrolled in this study. Perception of vibration, pressure, temperature, ankle brachial index, waist-hip ratio, body fat percentage, serum 25(OH) vitamin D₃(25(OH)D₃), 1.25(OH)₂ vitamin D₃(1.25(OH)₂D₃), blood glucose, glycated hemoglobin A1c(HbA1c), blood lipid, blood pressure were tested. The balance degree of all subjects were evaluated by Berg balance scale, the cases and number of falls of all subjects in last 12 months were recorded. Statistical analysis was performed by using Spearman correlation analysis and multiple linear regression analysis.

In DM group, the incidence of falling (27.8%(18/97) vs 10.17%(6/59), χ ²=6.230) and number of falls ((0.41±0.08) vs (0.12±0.05), t=2.570) were significant higher, while the Berg balance scale scores(48.0±1.8 vs 50.4±1.4, t=-8.900), perception of vibration((17±5) vs (13±3)V, t=4.970), ankle brachial index(0.79±0.11 vs 0.97±0.16, t=-8.430), pressure sense(normal ratio 68.0% vs 89.8%, χ ²=9.627), temperature sense(normal ratio 52.6% vs 69.5%, χ ²=4.338) decreased significantly when compared to those in control group(all P<0.05). Spearman correlation analysis showed that Berg balance scale scores was negatively correlated with vibration perception(r=-0.760, P<0.05), positively correlated with pressure sense(r=0.556, P<0.05) and ankle brachial index(r=0.472, P<0.05). Multiple linear regression analysis showed that vibration perception and pressure sense were independent risk factors for Berg balance scale scores (β=-0.702, 0.251, bothP<0.05).

The balance degree in patients with long-duration T2DM aged 65 years and above declines obviously, vibration perception and pressure sense are independent risk factors for balance degree in those patients.

To investigate whether metformin and liraglutide had a synergistically protective effects on palmitic acid-induced endothelial cell oxidative damage.

Human umbilical endothelial cell, which were exposed to palmitic acid for inducing endothelial cell dysfunction, were treated with metformin and/or liraglutide for 24 h. Intracellular level of reactive oxygen species (ROS) was detected by flow cytometry. Supernatant nitric oxide (NO) concentration was measured by nitrate reductase method. One-way ANOVA and Q test were applied to analyze the differences among the groups.

Compared with control group, 0.25 and 0.50 mmol/L palmitic acid significantly increased intracellular ROS levels ((125±17)%, (189±8)% vs 100%, P<0.05), and decreased supernatant NO levels ((89.9±6.2)%, (79.8±4.8)% vs 100.0%,P<0.05). Either metformin (0.5-1.0 mmol/L) or liraglutide (10-100 nmol/L) treatment alone could significantly prevent the augmented ROS levels and reduced NO levels induced by 0.5 mmol/L palmitic acid. Mono-treatment with low dose of metformin (0.1 mmol/L) or liraglutide (3 nmol/L) did not alter the effects of 0.5 mmol/L palmitic acid on ROS and NO production. However, combination treatment with these doses of the agents significantly prevented the increased ROS levels and decreased NO levels induced by 0.5 mmol/L palmitic acid, shown as decrease of ROS level ((158±31)% vs (250±27)%,P<0.05) and increase of NO level ((91.7±30.6)% vs (82.3±5.0)%,P<0.05).

Metformin and liraglutide have a synergistic effects in protecting endothelial cell from palmitic acid-induced oxidative damage.

To explore the mechanism of the effect of different glucose rising speed on hypoglycemic brain injury in rats.

A total of 36 male SD rats (weight: 250-300 g) were divided into 6 groups with simple random sample: the blank group, sham group and 4 experimental groups, 6 rats in each group.The blank group was subjected to no disposal, the sham group was given femoral vein infusion of glucose and intraperitoneal injection of insulin to maintain normal blood glucose.The experimental groups were given femoral vein infusion of glucose with different speed after hypoglycemia induced by insulin injection.According to the glucose concentration after 1 hour of vein glucose infusion, the experimental groups were further divided into 4 groups (>1.0-3.0, >3.0-6.0, >6.0-9.0 and >9.0 mmol/L group). Western blotting was used to detect the protein expression levels of gene Bax and Bcl-2. Flow cytometry was used to detect the Ca²⁺ concentration in the neurocyte in hippocampus and cerebral cortex of the different groups.Comparison of measurement data among groups was done by using one-way analysis of variance.

Ratio of Bax to Bcl-2: compared with those in blank group and sham group, Bax/Bcl-2 in cerebral cortex and hippocampus in 4 experimental groups increased significantly (F=265.8, 42.7, both P<0.05), >9.0 mmol/L group had the highest Bax/Bcl-2, >1.0-3.0 mmol/L group had the second highest.There was significant differences in Bax/Bcl-2 among the 4 experimental groups (F=212.1, 27.4, both P<0.05). Ca²⁺ concentration: compared with those in the blank group and sham group, the Ca²⁺ concentration in cerebral cortex and hippocampus in 4 experimental groups increased significantly (F=79.8, 355.0, both P<0.05). >9.0 mmol/L group had the highest and >1.0-3.0 mmol/L group had the second highest level of Ca²⁺ concentration.There was significant differences in Ca²⁺ concentration among the 4 experimental groups (F=50.1, 71.1, both P<0.05).

Both too fast and too slow glucose rising speed will aggravate the hypoglycemic brain injury.

To evaluate the efficacy and safety of insulin combined with vildagliptin in type 2 diabetes mellitus (T2DM) patients with moderate renal impairment.A total of 143 T2DM patients with moderate renal impairment and poorly controlled blood glucose were included from December 2012 to November 2013 in out-patients or in patients of the Metabolic Disease Hospital of Tianjin Medical University and Jiefang Road Health Service Center, Binhai New District, Tianjin.On the basis of their existing insulin therapy, vildagliptin (50 mg once daily) was added to these patients for 12 weeks.Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), estimated glomerular filtration rate (eGFR), hemoglobin (Hb) and insulin dosage from baseline to week 12 were compared and adverse events and satisfaction of patients and doctors were assessed.132 patients completed this study.After the treatment, the levels of HbA1c in patients with moderate renal impairment were decreased by an average of 0.7% ((8.4±0.8)% vs (7.7±1.2)%, t=7.515), FPG decreased 1.8 mmol/L ((10.6±2.6) vs (8.8±1.4) mmol/L, t=9.476) and insulin dosage lowered 8 U ((51±16) vs (43±15) U/d, t=4.421, all above P<0.05). Hb and eGFR were not changed after treatment (P>0.05 all above). During the study, there was no occurrence of pancreatitis, death and other serious adverse effect.The satisfactions with vildagliptin treatment in patients with moderate renal impairment were 94.7% for physician, while were 94.0% for patients themselves.Vildagliptin 50 mg once daily is a well-tolerance and safety treatment option for patients with inadequately controlled T2DM and moderate blood glucose level in moderate renal impairment patients.

To observe the clinical effects of liraglutide monotherapy in the treatment of obese or non-obese newly diagnosed patients with early-onset type 2 diabetes mellitus(T2DM). In this study, 63 obese patients and 37 non-obese patients with early-onset T2DM were chosen to be treated with 1.2 mg liraglutide monotherapy for 12 weeks.Follow-up interviews were conducted at three stages respectively in 2, 6 and 12 week.Comparisons were made between the index changes in each patient before and after the treatment using independent samples t test.The results showed that: (1) After 12 weeks of treatment, comparing with the baseline levels, the body weight of group of obese patients decreased (from (89±13) kg to (84±12) kg, and group of non obese patients decreased from (66±9) kg to (64±8) kg); The fasting plasma glucose(FBG) of group of obese patients decreased from (10.3±1.8) mmol/L to (6.6±0.8) mmol/L, and which in group of non-obese patients decreased from (10.1±1.9) to (7.7±0.8) mmol/L.(2)The level of 2-hour plasma glucose (2 h PG), glycosylated hemoglobin A1c (HbA1c), total cholesterol(TC), triglyceride(TG), low-density lipoprotein- cholesterol (LDL-C) decreased, fasting insulin(FINS), fasting C peptide(FCP) group of obese patients increased(t=-2.093-7.810, all P<0.05). The non-obese group patients TC, LDL-C, HDL-C also improved, but the differences were not statistically significant (t=1.315-1.870, P<0.05). (3)After 12 weeks of treatment, comparing with the baseline levels, group of severe obesity patients apparently improved on body weights, 2 h PG, HbA1c ((92±13)to (98±14) kg, (8.2±1.9)to (15.0±2.6) mmol/L, (6.4±1.0)% to(9.5±1.2)%,t=3.079, 7.886, 5.081, all P<0.05). The other indexes were improved to some extent, but the differences were not statistically significant. That means liraglutide monotherapy has obvious improvement on body weight, plasma glucose level and islet β cell function in newly diagnosed obese patients with early-onset T2DM, especially in severe obesity patients.

To analyze the clinical features of the diabetes combined with primary pulmonary tuberculosis and the relationgship with the level of the diabetes control in the diabetes.There were 544 cases who were the hospitalized patients of diabetes combined with primary pulmonary tuberculosis in our hospital from January 1, 2011 to December 31, 2012.According to the glycosylated hemoglobin (HbA1c) after admission, the patients were divided into group Ⅰ (n=65), group Ⅱ (n=479). There were 437 cases who were the primary pulmonary tuberculosis without diabetes randomly selected in the same period as group Ⅲ (the control group). Comparisons were taken on the sputum positive rate and the characteristics of pulmonary lesions between the three groups.Group t test for measurement data, Multiple linear regression analysis for the linear dependence of measurement data, χ² test for count data.The results showed the sputum positive rate in group Ⅱ (88.5%(424/479)) was much higher than group Ⅰ(52.3%(34/65) )and group Ⅲ(50.6%(221/437), χ²=163.76, P<0.01). The discovery rate of caseous lesions in group Ⅱ (88.1%(422/479)) was much higher than the group Ⅰ(50.8%(33/65)) and group Ⅲ(47.6%(208/437),χ²=180.10, P<0.01). The discovery rate of multiple cavities in group Ⅱ was much higher than the group Ⅰ and group Ⅲ (56.4%(270/479), vs 23.1%(15/65)vs 22.4%(98/437),χ²=118.07, P<0.01). The discovery rate of worm-eaten-like cavities in group Ⅱ was much higher than group Ⅰ and group Ⅲ (24.8%(119/479) vs 12.3%(8/65)vs 11.2%(49/437),χ²=30.34, P<0.01). The discovery rate of caseous cavities in the Ⅲ group was much higher than group Ⅰ, group Ⅱ and group Ⅳ (52.4%(251/479)vs 21.5%(14/65)vs 26.3%(115/437),χ²=74.20, P<0.01). In a conclusion, there is a close correlation between the clinical features and the level of the diabetes control in the diabetes combined with primary pulmonary tuberculosis.

Diabetes mellitus is a common chronic disease, which requires good disease management to prevent and treat acute and chronic complications, improve the quality of life of patients and prolong the life span of patients. Diabetes management includes diet control, reasonable exercise, blood sugar monitoring, diabetes education and application of hypoglycemic drugs, etc. Highly individualized management principles should be adopted^[1]。 Due to the high prevalence of diabetes and the lack of professional management personnel, it is still difficult to rely on existing medical resources for individualized management. As a new medical mode, mobile health (moblie health, mHealth) has received more and more attention in the field of diabetes management by rationally allocating medical resources through information technology and improving the utilization rate of medical resources.

The regulation of blood glucose is a very important link in the maintenance of glucose homeostasis. The decrease of islet β cell capacity will cause insufficient insulin secretion in the body, which will lead to imbalance of glucose homeostasis, which plays an important role in the occurrence and development of diabetes. The development of diabetes is very insidious, Meier et al.^[1]The latest research shows that when prediabetes and diabetes are diagnosed, beta cell capacity has actually decreased by 21% and 64% respectively. A meta-analysis shows that 5% to 10% of prediabetics progress to diabetes every year^[2]However, few people have blood sugar reversal to normal after glucose metabolism disorders. Therefore, we need to give early warning of the decrease of β cell capacity and give effective intervention to achieve the purpose of early saving β cells and blocking the occurrence and development of diabetes.

It is well known that insulin resistance is one of the important pathophysiological features throughout the development of type 2 diabetes mellitus (T2DM), which means that the target tissue is less sensitive to insulin. In order to meet the demand, insulin secretion will exceed normal levels until islet beta cell function gradually declines due to long-term high-load work. At the cellular level, insulin resistance can be understood as a reduction in biological effects per unit insulin, which not only manifests in the disorder of glucose uptake and utilization by peripheral tissues, but also causes weakened hepatic glycogen synthesis and increased glycogenolysis. Recent studies have found that chronic inflammation and the activation of inflammatory signaling pathways reduce the sensitivity of target tissues to insulin, and various inflammatory factors and adipokines are involved^[1,2]。 At the same time, some studies have shown that the innate immune system has a certain relationship with insulin resistance^[3]。 Toll-like receptor 4 (TLR4) is mainly distributed on the surface of various cells of the immune system, and is an indispensable and important part of the signal transduction process of the innate immune system. After binding to ligands, it will activate intracellular signaling pathways, resulting in the synthesis and release of inflammatory factors. At the same time, TLR4 is also expressed in insulin resistance target organs and tissues, such as adipose tissue, liver, skeletal muscle, etc. Its activation can directly affect the insulin sensitivity of target tissues^[4]。 This paper briefly reviews the recent research progress on the mechanism of insulin resistance between TLR4 and T2DM.

Diabetes mellitus (DM) is a chronic metabolic disorder. DM microvascular disease is a common and serious chronic complication of DM, which seriously affects the quality of life of DM patients^[1]。 Clinically, skin and soft tissue complications caused by DM occur from time to time, and its treatment is quite difficult. The mechanism of skin and soft tissue complications in DM is complex, and ischemia and hypoxia are their common characteristics^[2]。 Studies have shown that neovascularization disorder is one of the main pathological features of DM^[3,4]The disorder of neovascularization after ischemia and hypoxia induction is one of the main causes of skin and soft tissue regeneration and repair disorders in DM^[5]。 In recent years, cell therapy has made significant progress in the prevention and treatment of DM and its complications^[6,7]。 The results showed that vascular endothelial cells, endothelial precursor cells and bone marrow stem cells could promote neovascularization in ischemic tissue to varying degrees^[8,9,10,11]。 Adipose stem cells (ASCs) have some effects on the repair of ischemic tissues^[12]。 This article reviews the related research of ASCs and its application progress in skin and soft tissue complications of ischemic-hypoxic DM.

Newly diagnosed diabetic foot disease has a mortality rate of about 50% within 5 years, which is worse than the prognosis of breast cancer, prostate cancer and Hodgkin's lymphoma. Guidelines for the outpatient treatment of diabetic foot disease have been issued, while the treatment of inpatients with diabetic foot disease is rarely mentioned. In 2013, international first-class experts in the fields of internal medicine, endocrinology, podiatry, orthopedics and plastic surgery, and nursing cooperated to formulate the Guidelines for Inpatient Diabetic Foot Disease based on evidence-based medical evidence and their respective experiences in treating podiatry, aiming at providing effective guidance for the cure of foot ulcers for inpatients with diabetic foot disease, so that inpatients can smoothly transition to outpatients^[1]。

Sponsored by the Blood Glucose Monitoring Group of Diabetes Branch of Chinese Medical Association and hosted by Shanghai Medical Association and the Sixth People's Hospital affiliated to Shanghai Jiaotong University, the "Annual Meeting of Blood Glucose Monitoring Group and the Fifth International Forum on Blood Glucose Monitoring" was held in Shanghai from December 13th to 14th, 2013. More than 300 experts in related fields from all over the country attended this forum. At the opening ceremony of the meeting, Professor Jia Weiping, chairman-designate of Diabetes Branch of Chinese Medical Association, Professor Chen Liming, leader of blood glucose monitoring group, and Professor Yan Shijie, executive vice president and secretary general of Shanghai Medical Association, delivered speeches respectively. The topics of the previous four forums were "Information Changes Cognition", "Combining Vertical and Horizontal View", "Information Changes Cognition Monitoring Leads Treatment", and "Complementing each other with each other"^[1,2,3,4]The theme of this forum is "studying things to achieve knowledge and gathering consensus", which means adhering to the spirit of respecting truth-seeking and exploring the principles of things. At the forum, Professor Ian Blumer from Canada and Professor Oliver Mast from Germany gave wonderful reports on the international progress of blood glucose monitoring and the application of new technologies respectively. Professors such as Bao Yuqian, Zhou Xianghai, Pan Baishen, Li Hong, Wang Chun, Li Yanbing, Ma Jianhua, Wang Yufei, Li Qiang, Gao Zhengnan, Kuang Hongyu and Zheng Fenping made in-depth analysis on the cutting point of Chinese glycosylated hemoglobin (HbA1c) in the diagnosis of diabetes, the consistency of HbA1c detection, the current status of hypoglycemia diagnosis and treatment process, perioperative blood glucose management, ambulatory blood glucose monitoring and blood glucose fluctuation and many other hot spots.

Linagliptin, a novel dipeptidyl peptidase IV (DPP-4) inhibitor, has been marketed in China. As an important choice for hypoglycemic treatment of patients with type 2 diabetes mellitus (T2DM), linagliptin not only effectively lowers blood sugar, but also is convenient to take. Take it orally once a day, with few adverse reactions. This article mainly reviews its safety and application in special populations.

Human bone morphogenetic protein 9 (BMP-9) is highly expressed in liver cells. After insulin injection, it can quickly exert the hypoglycemic effect, and the effect gradually weakens within 2 h; However, the maximum hypoglycemic effect of recombinant human BMP-9 on diabetic mice occurred around 30 h after injection. The administration of BMP-9 antibody induced the development of glucose tolerance and insulin resistance in rats. The above results indicate that BMP-9 plays an important role in the regulation of glucose homeostasis, but its mechanism of action is still unclear. At present, it is believed that BMP-9 may participate in the regulation of glucose homeostasis by regulating the expression of various enzymes.

The relationship between body mass index (BMI) and mortality in patients with type 2 diabetes remains unclear, and the results of some studies raise the "obesity paradox": studies have found that overweight or obese people have a decreased mortality rate compared with normal weight people. However, most of these studies have certain limitations due to factors such as small sample size, poor control of smoking status and underlying chronic diseases.

Obesity has now become a global health problem. In general, obesity is classified into abdominal obesity (VISC) and subcutaneous obesity (SubQ). Abdominal obesity, especially those with normal BMI, is closely associated with increased mortality. Abdominal obesity is closely related to type 2 diabetes, and the increase of subcutaneous fat is relatively more beneficial.

Perinatal nutritional and drug interference can have a sustained effect on white adipose tissue function, thereby altering the susceptibility to obesity in adulthood. Previous studies have proved that saccharin, a nutrition-free sweetener, can inhibit the lipolysis of mature adipocytes and stimulate fat synthesis. Therefore, the aim of this study was to confirm whether exposure to saccharin by maternal lactation in newborn rats increases their risk of obesity due to overeating.