Volume 11 · Issue 09 · 2019

Exercise therapy is one of the key links in the comprehensive treatment of diabetes, which can significantly reduce blood sugar, improve metabolic abnormalities and reduce the risk of cardiovascular and cerebrovascular adverse events in diabetic patients. However, there are still many difficulties in the actual clinical promotion process. Most hospitals are difficult to provide sufficient professionals and sports venues for sports management, and the overall management quality is low. The integration of sports and medicine means that sports and medicine give full play to their unique technical advantages, integrate sports and medical technology into the treatment of diabetes, solve the problem of shortage of sports venues, equipment and talents, realize resource sharing and improve the quality of sports management. At present, there are four modes of physical integration in China: sports club, community physical fitness testing center, hospital health guidance center and the combination of government and market. In the model of hospital health guidance center, Peking University model and Southeast University model have made useful explorations, and the key link in their implementation is to solve the problem of right to speak and information management.

Diabetes exercise rehabilitation is the cornerstone of disease management. However, worldwide, the level of physical activity or exercise of diabetic patients is generally below the recommended levels in the guidelines. How to make patients improve and maintain a certain level of physical activity or exercise, rather than the improvement effect of a specific exercise on patients, is the main direction of collaboration between medical and sports workers under the policy of "integration of physical medicine". Therefore, while addressing the external barriers to movement, the more prevalent internal barriers in particular require high attention. Exercise is not a necessary condition for blood glucose improvement. For example, when glycosylated hemoglobin reaches a certain decrease to judge the effectiveness of intervention research methods, the content of intervention rather than intervention methods play a more decisive role. In the choice of sports rehabilitation research goals, improving patients' exercise compliance should be the main focus. When carrying out specific research, attention still needs to be paid to the practicality design of the research. Through consciously close to the clinical environment to carry out sports rehabilitation research, to ensure the practicality, validity and consistency of the research results when translating to the clinic.

Shared clinic is a continuous personal medical service carried out in a group environment. It is a new patient-centered and value-oriented diagnosis and treatment model that has emerged in recent years, and is mainly suitable for patients with chronic diseases. As a chronic progressive disease with high incidence and dependence on drugs, lifestyle and regular monitoring, diabetes is one of the most suitable services for the shared medical model. The implementation of this model can play a positive role in the improvement of patients' blood sugar control, self-management efficiency, doctor-patient satisfaction, medical efficiency and service value. However, the limited medical and nursing resources make the optimal applicable objects of shared outpatient clinics unclear. In the future, large sample clinical trials should be conducted, and at the same time, with the help of active cooperation among various disciplines, a shared medical chronic disease management model suitable for China's national conditions should be explored, so as to more accurately and effectively deal with more and more complex patients.

To investigate the effects of remote exercise rehabilitation support based on behavior change techniques on exercise self-efficacy and glycosylated hemoglobin A_1c (HbA_1c) in patients with type 2 diabetes mellitus (T2DM).

A total of 381 patients with T2DM who were followed up for more than 6 months in Peking University First Hospital Diabetes Shared Care Clinic from January to December 2018 were enrolled. The patients who voluntarily received a 3-month behavior change techniques based remote exercise intervention were assigned to exercise intervention group [45 cases, (50.4±12.8) year-old, female 24 cases (53.3%), diabetes duration was 4.6 (0.8, 12.0) year] and the rest were in non-exercise intervention group [336 cases, (57.8±11.6) year-old, female 155 cases (46.1%), diabetes duration was 10.3 (2.8, 16.0) year]. After evaluated by exercise coach, patients in exercise intervention group with higher baseline self-efficacy scale scores only received exercise reminders and electronic exercise prescription, and those with lower self-efficacy received individualized video exercise prescription based on behavior change techniques. Including age, disease duration, gender, body mass index, and baseline HbA₁c were used as covariates, the propensity score analysis was used to compare the change of HbA_1c at six months for patients with uncontrolled baseline HbA_1c between exercise intervention group and non-exercise intervention group. The t test and Wilcoxoh test were used for data analysis.

Compared with baseline, both exercise self-efficacy score [40 (31, 54) vs 55 (26, 83) points, Z=-2.229, P=0.026] and exercise self-management ability score [2 (2, 4) vs 4 (3, 5) points, Z=-2.401, P=0.016] were significantly improved after six month in low exercise self-efficacy group. HbA_1c were significantly lower in the exercise intervention group compared with baseline (8.9%±2.0% vs 6.9%±0.8%, t=5.723, P<0.000 01).

In the context of effective multidisciplinary management of diabetes, implementation of behavioral change technique-based remote exercise support can improve exercise self-efficacy and HbA_1c in patients with poor controlled T2DM.

To explore the application effect of portable wearable device (including muscle oxygen monitor, heart rate armband combined with mobile APP) and exercise management platform in patients with type 2 diabetes mellitus (T2DM).

A total of 66 patients with T2DM were recruited from Department of Endocrinology of the First Affiliated Hospital, Henan University of Science and Technology between May 2017 and June 2018, and randomly divided into the test group (34 cases) and the control group (32 cases). Patients in the test group received portable wearable devices and sport management platform, and the controls received routine sport education. Levels of plasma glucose and lipid, muscle oxygen and heart rate before and after management were compared between these two groups. The t test and chi-square analysis were used for comparison between groups.

After management, levels of glycated hemoglobin A_1c (HbA_1c) and fasting plasma glucose (FPG) in the test group were lower than those in the control group [(7.34±1.61)% vs (6.17±0.53)%, (8.17±2.48) vs (6.30±1.19) mmol/L, respectively; t=-3.248, -3.644, both P<0.05]. The maximum heart rate and the maximum exercise intensity were both higher than those in the control group [(139.00±16.28) vs (129.84±13.00) times/min and 0.80±0.08 vs 0.75±0.05, respectively; t=-2.400, -2.639, both P<0.05]. By increasing speed at 4 min×4 stage of treadmill, the average muscle oxygen ratio and the decrease of muscle oxygen ratio in the test group were both better than those in the control group [(54.79±14.12)% vs (58.00±14.14)%, and (24.56±19.58)% vs (19.03±15.68)%, respectively; t=-4.541, -2.563, both P<0.05].

Intervention combined the portable wearable devices with the sport platform can optimize the exercise management and help to control blood glucose and improve muscle oxygen ratio in patients with T2DM.

To compare the efficacy of dapagliflozin versus sitagliptin in overweight and obese type 2 diabetic patients with poor blood glucose control using insulin therapy.

A total of 98 patients with body mass index >24 kg/m ², waist circumference (male>90 cm and female>85 cm), glycosylated hemoglobin A_1c (HbA_1c)≥8% were enrolled from October 2017 to April 2018 in metabolic management center of Tianjin 4th Central Hospital. All subjects were randomly assigned to receive additional dapagliflozin 10 mg (n=48) or sitagliptin 100 mg once a day (n=50) in a 24-week study. 11 patients withdrew from the study. HbA_1c, fasting plasma glucose, 2 h postprandial plasma glucose, weight, waist circumference, blood pressure, and daily insulin dosage were assessed and checked at baseline and 24th week. Paired t test was used for comparison before and after treatment in the same group, and independent sample t test was used for comparison between groups.

A total of 87 patients(dapagliflozin group 42 vs sitagliptin group 45) completed the survey. Compared to the baseline, after 24-week treatment, the HbA_1c decreased between dapagliflozin group and sitagliptin group had statistical significance [(2.27±0.85)% vs (1.75±1.50)%, t=2.031, P<0.05]. The daily insulin dosage decreased between dapagliflozin group and sitagliptin group had statistical significance [(36.1±11.2) vs (41.1±12.8) U, t=2.163, P<0.05]. The proportion of patients without gain waist circumference was 78.6% in dapagliflozin group and 48.9% in sitagliptin group (χ²=8.231, P<0.01).

Dapagliflozin and sitagliptin applied to patients with inadequately glycemic controlled and overweight or obese patients with insulin therapy can beneficial to regulate glucose. Dapagliflozin is superior on glucoce control and drop of waist circumference and daily insulin dosage to sitagliptin.

To expore the functional changes of islet α- and β-cells in early-onset type 2 diabetes mellitus.

Forty patients with early-onset type 2 diabetes mellitus (EOD group), 40 patients with late-onset type 2 diabetes mellitus (LOD group) and 30 normal controls (NC group) were recruited in this study and received oral glucose tolerance test, insulin and glucagon release tests. Blood glucose, insulin and glucagon levels were compared before and after glucose loading. Analysis of variance was used for comparison between groups, and t test or Mann-Whitney U test were used for pairwise comparison.

There were no significant differences in blood glucose levels between EOD and LOD group at each time point (t=-1.101-0.007, both P>0.05); Fasting insulin and fasting glucagon in EOD group were significantly higher than those in LOD and control groups (U=140.000-218.000, both P<0.01); HOMA-IR in EOD group were higher than those in LOD and NC group (t=4.980, 2.094, both P<0.05), ISI_Matsuda in EOD group were lower than those in LOD and NC group (t=-4.315, -2.146, both P<0.05), HOMA-β and ΔI30/ΔG30 in EOD group were higher than those in LOD group but lower than those in NC group (t=2.140-9.166, both P<0.05), AUCIns in EOD group were higher than those in LOD group (t=-1.527, 2.319, P<0.05), AUCGcg and Gcg/Glu in fasting and 1, 2 h after glucose loading in EOD group were higher than those in LOD group (2 h Gcg/Glu in EOD group was 1.4±0.7, and was 1.0±0.8 in LOD, t=2.113-3.354, both P<0.05).

β-cell function in EOD patients is better than that in LOD patients. However, compared with LOD patients, the insulin resistance and the islet α cell dysfunction are higher in EOD patients, including high levels of fasting glucagon, lower inhibition effect of blood glucose on glucagon, which may be one of the reasons for the early-onset type 2 diabetes mellitus.

To evaluate the efficacy and safety of metformin in patients with hyperglycemia in pregnancy.

A total of 135 patients who were diagnosed with gestational diabetes mellitus (GDM), overt diabetes mellitus (ODM), or pre-gestational diabetes mellitus (PGDM) at the endocrinology outpatient clinic of Shengjing Hospital affiliated to China Medical University were recruited. Patients were divided into conventional treatment group (n=60, including those received insulin treatment only) and metformin group (n=75, including those received both insulin and metformin treatment). The differences between the two groups were compared using Student′s t-test or Mann-Whitney U test, and the differences between multiple groups were tested by ANOVA or Kruskal-Wallis H test. Categorical variables were compared using Chi-square test.

Regardless of the type of hyperglycemia in pregnancy, there was no significant difference in weight gain during pregnancy between the groups. The increase of basal, mealtime and total insulin dosage in the metformin group of GDM and PGDM patients were significantly lower than those in the conventional treatment group [the increase of total insulin was 0.02 (0.00, 0.18) vs 0.07 (0.06, 0.37) U/kg and 0.41 (0.15, 0.92) vs 0.73 (0.36, 1.10) U/kg, respectively, Z=-6.829, -5.756, both P<0.05]. The increase of mealtime and total insulin dosage in ODM metformin group were also significantly lower compared with control group [the increase of total insulin dosage was 0.41 (0.24, 0.55) vs 0.51 (0.36, 0.98) U/kg, Z=-4.775, P<0.05]. In patients with insulin dosage greater than 100 U/d or patients with pre-gestational body mass index (BMI) greater or equal to 28 kg/m², the increases of insulin dosage in the metformin group was also significantly lower than those in the conventional treatment group (Z=-6.866--5.080, all P<0.05).

Combination with metformin during pregnancy can reduce insulin dosage, especially for patients with high insulin dosage or obesity.

To investigate the characteristics of glucose metabolism in patients with growth hormone (GH) secreting adenomas and the impact of trans-sphenoid surgery.

Preoperative and postoperative clinical information of patients with GH secreting adenomas who underwent trans-sphenoidal surgery in department of neurosurgery of Huashan Hospital from November 2011 to April 2016 were collected. Preoperative prevalence of abnormal glucose metabolism was analyzed; insulin resistance and β cell function were compared among different glucose tolerance groups; changes in the characteristics of glucose metabolism after operation were analyzed. Subgroup analysis was performed according to the recovery of GH and insulin-like growth factors-1 (IGF-1) after operation, and changes of glucose metabolism in different subgroups after operation were compared. Logistic regression analysis was used to analyze the risk factors of glucose metabolism outcome after operation.

A total of 81 patients were enrolled in this study. The preoperative prevalence of abnormal glucose metabolism was 69.1% (56/81). There was no difference in insulin resistance among normal glucose tolerance (NGT) group, pre-diabetes mellitus (preDM) group and diabetes mellitus (DM) group. Homeostasis medel assessment of insulin resistance [66.25(28.90, 129.76)%] and insulinogenesis index [2.24(1.34, 9.97)] in DM group were significantly lower than those in preDM group [195.30(141.00, 260.00)%, 32.65(8.56, 48.35), respectively] and NGT group [176.25(140.63, 218.14)%, 30.69(11.98, 51.38), respectively] (F=27.050, 20.690, both P< 0.05). 67.9%(38/56) of patients with abnormal glycometabolism recovered to NGT after operation. Compared with pre-operation, glyacted hemoglobin (HbA_1c) in complete remission group and GH remission group decreased significantly after operation [(6.4±1.5)% vs (5.7±0.7)%, (6.2±1.2)% vs (5.5±0.5)%, respectively, t=3.780, 3.378, both P<0.05], with no significant change in non-remission group. In the complete remission group, GH remission group and non-remission group there are 4, 3 and 2 indexes reflecting β-cell function improved respectively. Logistic regression analysis showed that baseline HbA _1c and biochemical remission state were correlated with the outcome of glucose metabolism after operation (all P<0.05).

Impairment of β cell function is the decisive factor for developing DM in patients with GH secreting adenomas. Preoperative HbA _1c level and postoperative biochemical remission states affect the outcome of glucose metabolism after operation.

To observe the effect of saxagliptin on the expression of integrin avβ5 in serum and liver tissues of type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) and the sinusoidal capillarization, and to explore the pathogenesis of diabetes mellitus complicated with fatty liver and the possible protective mechanism of saxagliptin on diabetes with fatty liver.

Rats models of T2DM with NAFLD were established by feeding on a high-fat diet combined with low-dose streptozotocin (STZ) intraperitoneal injection. Fifty male SPF Wistar rats (10 in each group) at 10 weeks of age were divided into 5 groups: normal control (NC), NAFLD, T2DM with NAFLD model control group, integrin avβ5 inhibitor intervention group and saxagliptin intervention group. The rats of the avβ5 inhibitor intervention group were injected with the integrin avβ5 inhibitor lentiviral plasmid (10⁹ TU/ml, 20 μl/day) via the tail vein. The rats of saxagliptin intervention group were treated with saxagliptin (daily dose of 10 mg/kg) gavage for 6 weeks, and the rats of the control group were given the same volume of normal saline. After the treatment for 6 weeks, fasting blood glucose, serum insulin, blood lipids, liver function, liver index and pathological changes were evaluated in all the rats, and the expressions of integrin avβ5 and Vn in the liver tissue were detected with immunohistochemistry and western blotting. Ultrastructure of the liver was detected by transmission electron microscopy. The expression levels of integrin avβ5 and Vn mRNA were detected by RT-PCR. The serum levels of integrin avβ5 in the rat were detected by ELISA. T test was used for comparison between groups.

(1) Compared with the model group, saxagliptin significantly reduced the serum level of integrin avβ5 in the rats (0.47±0.06 vs 0.96±0.12,t=3.36, all P<0.05); (2) The protein expression levels of integrin avβ5 and Vn in the liver tissue of diabetic rats with fatty liver were significantly higher than those in the normal control group, but the levels were significantly decreased after the treatment with saxagliptin (t=3.16-9.86, all P<0.05). The mRNA expression levels of integrin avβ5 and Vn were consistent with those protein expression (t=3.50-8.33, all P<0.05); (3) Transmission electron microscopy results show: in the model group, the basement membrane of sinusoidal endothelial cells is thickened, continuous and windowless. Moreover, the endoplasmic reticulum in the cytoplasm of hepatocytes proliferates or expands, the mitochondrial sputum decreases or dissolves, and the Disse′s gap widens. And a large amount of collagen fibrosis can be seen in the gap. The basement membrane gradually returns to a basement membrane with a window or discontinuity or thinning, and the expanded endoplasmic reticulum and swollen mitochondria are significantly improved after the treatment with integrin avβ5 inhibitor or saxagliptin; (4) Compared with the model group, the levels of liver coefficient, aspartate aminotransferase, alanine aminotransferase, fasting insulin, and homeostatic model assessment for insulin resistance were significantly decreased in the integrin avβ5 inhibitor or sax intervention group (t=6.11-9.7, all P<0.05).

Saxagliptin protects diabetes with nonalcoholic fatty liver disease by inhibiting the expression of integrin avβ5 in serum or liver tissue of the rats and integrin avβ5-induced sinusoidal capillarization.

To explore the effect and mechanism of high glucose environmenton mouse bone marrow-derived dendritic cells′ (DCs) differentiation, maturation, immune function, to further explore the role of DCs in inflammation of diabetic nephropathy.

Bone marrow mononuclear cells (MNCs) were isolated and cultured in the medium containing recombinant human granule macrophage colony stimulating factor (rhGM-CSF, 20 ng/ml) and recombinant human interleukin-4 (rhIL-4, 10 ng/ml). On 7th day, immature DCs were collected and cultured in RPMI1640 complete medium containing 5.5 mmol/L D-glucose, 30 mmol/L D-glucose, 30 mmol/L D-glucose+100 μg/ml NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) for 48 h, and then flow cytometry (FCM) was used to detect the phenotype of DCs. Cells were stimulated with DCs, allogeneic T lymphocytes were mixed in proportion and the reaction intensity of mixed lymphocytes was used to observe the effect on dendritic cell antigen presentation, lymphocyte proliferation, lymphocyte apoptosis. ELISA assay was adopted to detect cytokines concentration of cell culture supernatant. Western blot was adopted for detection of NF-κB activation. Student- t test was used to analyze the significance of the differences between the groups.

Compared with the normal control group, 30 mmol/L D-glucose significantly increased the activation of NF-κB in DCs (IκBɑ:0.29±0.18 vs 0.69±0.79,t=-1.27; p65: 0.87±0.18 vs 0.35±0.13, t=2.19; all P<0.01) and the expression of eCD11c, MHC class Ⅱ molecules, CD80, CD86 and CD40 on DCs (t=8.97-10.45, all P<0.05). It promoted the T lymphocyte proliferation (1∶100:1.80±0.23 vs 1.57±0.20, t=2.46; 1∶25:1.74±0.17 vs 1.32±0.18, t=2.82; 1∶10:1.59±0.25 vs 1.28±0.19, t=3.06; all P<0.05), weakened the T lymphocyte apoptosis rate (12±2 vs 44±13, t=4.03, P<0.05). And it promoted DCs′ secretion of cytokines IL-12, IFN-γ and TNF-α (t=3.68-7.68, all P<0.05), while the inhibition of NF-κB agent PDTC could block the above effects to varying degrees (allP<0.05).

High glucose can significantly increase the activation of NF-κB thereby promote the maturation of DCs, which accelerates and amplifies the inflammatory response. This may be one of the important mechanisms of dendritic cells in diabetic nephropathy.

Fulminant type 1 diabetes mellitus (FT1DM) is characterized by sudden hyperglycemia and rapid development of ketosis or ketoacidosis, elevated lipase or amylase, and near-normal glycosylated hemoglobin. It mostly occurs in female patients at 3 months after pregnancy and 1 week after delivery. This paper reports a patient with gestational diabetes mellitus who developed local allergy after insulin injection at the initial stage of treatment, but the blood glucose control was still stable; Sudden increase in blood sugar in the third trimester of pregnancy is considered as FT1DM. Due to obvious local allergy to various insulins and affecting insulin absorption, blood sugar control is poor. After replacing and adjusting insulin, Gula insulin pump is given to reduce blood sugar, and blood sugar control is stable.

As the composition and extension of chronic disease management system, the application of peer support in diabetes self-management support has been paid more and more attention. This article summarizes the application status of peer support in diabetes prevention and management at home and abroad, from the aspects of the connotation and system development of peer support, the choice of peer support, the framework of peer support training system, the intervention mode of peer support and its effect, etc. The existing empirical evidence has clearly shown the effectiveness of peer support in diabetes prevention and management, and it is necessary to further promote the application research based on "real world" to provide strategies and basis for the sustainable promotion of "peer support" model.

As a new combination of Internet industry and medical service industry, mobile medical care is gradually being applied to diabetes exercise management, mainly including three intervention forms: mobile phone SMS, smart phone APP (application) and wearable mobile devices. These three forms of intervention have achieved remarkable results in blood sugar control, health education, lifestyle adjustment, etc. of diabetic patients. Among them, wearable mobile devices have realized quantitative monitoring of exercise prescriptions, improving the exercise effect and safety. The new medical model of "Internet plus smart phone APP + wearable mobile device" has a good application prospect in diabetes management, but there is a lack of relevant research and development at present, and the laws and regulations are not perfect, so further exploration is needed.