The association between blood glucose levels of children with type 1 diabetes mellitus and parental educational levels based on mobile health APP / 中国医师杂志

Objective:To explore the correlation between blood glucose level and parental education level in children with type 1 diabetes mellitus (T1DM) based on mobile health APP.Methods:The data of T1DM children enrolled in China′s T1DM registration management program and registered to use TangTangquan ? were collected, as well as the blood glucose monitoring information uploaded quarterly after registration. Children were divided into low education group (middle school or below) and high education group (junior college or above) according to their parents′ education level. Blood glucose levels were compared between the two groups at different time points. Spearman correlation analysis and multivariate logistic regression analysis were used to evaluate the correlation between blood glucose level and parents′ education level in children with T1DM. Results:A total of 2 263 eligible children with T1DM were included and 1 246 were female (55.1%). The median age was 7.9(4.4, 11.4)years and T1DM duration was 0.07(0.02, 0.46)years. Among them, 1 513 cases were in the low-education group while 750 cases were in the high-education group. Within three years after registration, the glucose levels of each interval in the low-education group were increasing gradually (all P<0.05 except post-breakfast glucose). The glucose levels of each interval in the high-education group in the third year were lower than those in the low-education group (all P<0.05 except nocturnal glucose). The result of multivariate logistic regression analysis showed that after the adjustment of factors including T1DM duration and treatment, parental educational levels were still the separate related factors of premeal glucose, bedtime glucose and nocturnal glucose (premeal glucose: OR=0.385, 95% CI: 0.164-0.874, P=0.025; bedtime glucose: OR=0.444, 95% CI: 0.204-0.949, P=0.038; nocturnal glucose: OR=0.226, 95% CI: 0.582-0.747, P=0.020). Conclusions:The blood glucose levels of children with T1DM were negatively associated with parental educational levels. It is suggested that parental educational levels should be taken into consideration in the management of T1DM for children.

Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus

Background@#Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications. @*Methods@#We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR). @*Results@#Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P<0.05). @*Conclusion@#Although the prevalence of MetS in adult patients with T1DM in China was relatively low, patients with MetS were more likely to have DKD and DR. A comprehensive management including lifestyle modification might reduce their risk of microvascular complications in adults with T1DM.

KLF2 is a therapeutic target for COVID-19 induced endothelial dysfunction

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its mechanism being incompletely understood. Emerging evidence has demonstrated that the endothelium represents the Achilles' heel in COVID-19 patients and that endothelial dysfunction precipitates COVID-19 and accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. Primary human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) were treated with serum from control subjects or COVID-19 patients. Downstream monocyte adhesion and associated gene/protein expression was evaluated in endothelial cells exposed to COVID-19 patient serum in the presence of KLF2 activator (Atorvastatin) or KLF2 overexpression by an adenoviral vector. Here, we demonstrate that the expression of KLF2 was significantly reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1{beta} and TNF-, two cytokines observed in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis and reduced angiogenesis). Treatment of HPMECs with atorvastatin or KLF2 adenovirus ameliorate COVID-19 serum-induced increase in endothelial inflammation and monocyte adhesion by increasing KLF2 expression. Altogether, the present study demonstrates that genetic and pharmacological activation of KLF2 represses COVID-19 associated endothelial dysfunction, heralding a potentially new direction to treat endothelialitis accompanying COVID-19.

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial / 医学前沿

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.

Decline of SARS-CoV-2 specific IgG, IgM and IgA in convalescent COVID-19 patients within 100 days after hospital discharge

Monitoring the levels of SARS-CoV-2 specific antibodies such as IgG, M and A in COVID-19 patient is an alternative method for diagnosing SARS-CoV-2 infection and an simple way to monitor immune responses in convalescent patients and after vaccination. Here, we assessed the levels of SARS-CoV-2 RBD specific antibodies in twenty-seven COVID-19 convalescent patients over 28-99 days after hospital discharge. Almost all patient who had severe or moderate COVID-19 symptoms and a high-level of IgG during the hospitalization showed a significant reduction at revisit. The remaining patients who had a low-level IgG during hospitalization stayed low at revisit. As expected, IgM levels in almost all convalescent patients reduced significantly or stayed low at revisit. The RBD-specific IgA levels were also reduced significantly at revisit. We also attempted to estimate decline rates of virus-specific antibodies using a previously established exponential decay model of antibody kinetics after infection. The predicted days when convalescent patients RBD-specific IgG reaches to an undetectable level are approximately 273 days after hospital discharge, while the predicted decay times are 150 days and 108 days for IgM and IgA, respectively. This investigation and report will aid current and future studies to develope SARS-CoV-2 vaccines that are potent and long-lasting.

Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18 and SARS-CoV-2-specific IgA

The current global COVID-19 pandemic is caused by beta coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which already infected over 10 million and caused 500 thousand deaths by June 2020. Overproduction of cytokines triggered by COVID-19 infection, known as "cytokine storm", is a highly risk factor associated with disease severity. However, how COVID-19 infection induce cytokine storm is still largely unknown. Accumulating in vitro and in vivo evidence suggests that gut is also susceptible to COVID19 infection: Human intestinal organoids, an in vitro model which mimic the specific cell type and spatial structure of the intestine, were susceptible to SARS-CoV2 infection; A significant fraction of patients reported gut symptoms; Viral RNA may persist for more than 30 days and infectious virus could be isolated in fecal samples. The gastrointestinal tract is the primary site of interaction between the host immune system with symbiotic and pathogenic microorganisms. The bacteria resident in our gastrointestinal tract, known as gut microbiota, is important to maintain the homeostasis of our immune system. While imbalance of gut microbiota, or dysbiosis, is associated with multiple inflammation diseases5. It's possible that SARS-CoV-2 infection may lead to alternation of gut microbiota thus worsen the host symptom. IL-18 is a proinflammatory cytokine produced multiple enteric cells, including intestinal epithelial cells (IECs), immune cells as well as enteric nervous system, and was shown to increase in the serum of COVID-19 patients. Immunoglobin A (IgA) is mainly produced in the mucosal surfaces, in humans 40-60mg kg-1 day-1 than all other immunoglobulin isotypes combined, and at least 80% of all plasma cells are located in the intestinal lamina propria. Recent study showed that SARS-CoV-2 specific IgA in the serum is positively correlate with the disease severity in COVID-19 patients11. Here we investigated the alterations of microbiota in COVID-19 patients, and its correlation with inflammatory factor IL-18 and SARS-CoV2 specific IgA.

Tocilizumab treatment in severe COVID-19 patients attenuates the inflammatory storm incited by monocyte centric immune interactions revealed by single-cell analysis

ABSTRACTDespite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8+ T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab’s powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms.Competing Interest StatementJingwen Fang is the executive officer of HanGen BiotechView Full Text

Association of Population Migration and Coronavirus Disease 2019 Epidemic Control

Background and ObjectiveTo analyze the impact of different patterns of migration flow in two cities, Hefei and Shenzhen, on the epidemic and disease control of Coronavirus Disease 2019 (COVID-19), in order to provide insight for making differentiated controlling policies. MethodsWe collected demographic and epidemiological information of confirmed COVID-19 cases in Hefei and Shenzhen between January 19 and February 11, 2020, from data officially published by the provincial and municipal Centers for Disease Control and Prevention (CDC). From these data we calculated basic reproduction number R0 to reflect the rate of spread of COVID-19 in these cities. Aggregated data of population migration during the same period was extracted from Baidu Migration. The change of R0 in the two cites were analyzed and compared. Spearman correlation analysis between R0 and population inflow from epidemic focus were performed. ResultsA total of 157 confirmed cases was identified in Hefei by 24:00 February 11, 2020, with an average age of 44.4{+/-}15.6 years, 74 female (47.1%) and 386 confirmed cases were identified in Shenzhen, with an average age of 45.15{+/-}17.99 years, 202 female (52.3%). Significant difference in the proportion of imported cases between the two cities was observed (Hefei vs Shenzhen, 24.2% vs 74.9%, p=0.000). Before January 31 2020, during the initial stage of the Level 1 Response to Major Public Health Emergencies, there was no significant association observed in Shenzhen between R0 and the proportion of population inflow from the epidemic focus (P =0.260, r=-0.452); meanwhile in Hefei, such association was strong (P =0.000, r=1.0). However, after the initial stage of response, the situation reversed. A weak association was observed in Shenzhen between be R0 and the proportion of population inflow from the epidemic focus (P=0.073, r=0.536) but not in Hefei (P =0.498, r=0.217). ConclusionFollowing Level 1 Response, consistent decline of R0 of COVID-19 was observed in both Hefei and Shenzhen. Different patterns of disease spread were observed in the two cities, driven by different patterns of population migration. This indicated that population migration should be taken into consideration when we set controlling policy of a novel infectious disease.

The effect of mobile application based interactive peer support on glycemic control in patients with type 1 diabetes mellitus / 中华内科杂志

Objective@#To evaluate the effect of mobile application (APP) based interactive peer support on glycemic control in patients with type 1 diabetes mellitus (T1DM).@*Methods@#The data of the present study were from the largest mobile APP platform for patients with T1DM in China, Tangtangquan. Patients with T1DM who has registered in the APP for at least 1 year and had completed data entry were recruited. According to the monthly interaction index during the first year of APP registration (including four indicators: praise, comment, posting and collection), the eligible patients were divided into the high-interaction group and the low-interaction group. The changes from baseline of self-blood glucose monitoring frequency (SMBG), glycosylated hemoglobin (HbA1c), incidence of hyperglycemia and incidence of hypoglycemia were compared between the two groups after one year of using the APP.@*Results@#A total of 238 patients with T1DM with an age of (27±8) years were included. Among them, 77.3% (184/238) were female. The baseline SMBG [the low-interaction group (1.71±1.14) times/day vs. the high-interaction group (1.82±1.15) times/day] and HbA1c [the low-interaction group (6.72±0.99)% vs. the high-interaction group (6.76±1.04)%] were comparable between the two groups. After one year use of the APP, the frequency of SMBG in the high-interaction group was significantly higher than that in the low-interaction group [ΔSMBG (0.59+2.06) times/d vs. (0.08+1.69) times/d, t=4.280, P=0.04), and the reduction of HbA1c was more obvious in the high-interaction group [ΔHbA1c (-0.40+1.10)% vs. (-0.06+1.13)%, t=5.651, P=0.018] than in the lower-interaction group. The incidence of hyperglycemia in the high-interaction group was significantly lower than that in the low-interaction group [13.19(6.22,23.19)% vs. 17.69(10.56,30.49)%, Z=2.850, P=0.005]. There was no significant difference in the incidence of hypoglycemia between the two groups [4.62(2.14, 8.03)% vs. 4.83(2.06, 8.87)%, Z=1.276, P=0.204]. The correlation analysis showed that interaction index was significantly associated with the reduction of HbA1c and incidence of hyperglycemia.@*Conclusion@#Participation in interactive peer education via mobile APP may be beneficent for glycemic control in patients with T1DM.

Study on the correlation between smoking and hypothyroidism in iodine-suitable areas / 中华内分泌代谢杂志

Objective To explore the relationship between different smoking status and hypothyroidism in six iodine-suitable areas of China. Methods A total of 8187 residents were investigated by cluster sampling in six cities, and 7448 residents were included in the survey. The height, weight, waist circumference, and blood pressure were measured by filling out epidemiological questionnaire. Blood samples were collected to detect thyroid stimulating hormone ( TSH) , thyroid peroxidase antibody ( TPOAb) , and thyroglobulin antibody ( TgAb) . Results The mean TSH, TPOAb, and TgAb positive rates in passive smoking and active smoking groups were all lower than those in non-smoking group ( all P<0.01) . In the active smoking group, the TSH value decreased by 0.023 units for every unit increase in smoking index. The positive rates of TgAb and TPOAb in both passive smoking and active smoking groups were lower than those in non-smoking group (all P<0.01). Active and passive smoking reduced the prevalence of hypothyroidism (both P<0.01). Among women, the risks of clinical hypothyroidism and subclinical hypothyroidism were reduced in both active and passive smoking groups. Besides, the risk of subclinical hypothyroidism decreased significantly when the smoking index was more than 70. In male population, the risk of subclinical hypothyroidism in active and passive smoking group decreased. Besides, the risk of clinical hypothyroidism and subclinical hypothyroidism decreased significantly when the smoking index was more than 70. Conclusion Smoking in iodine-suitable areas may reduce TSH level and the positive rates of TPOAb and TgAb.

The validity and reliability of the revised Chinese version of diabetes self-management scales for adult type 1 diabetes patients / 中华内分泌代谢杂志

Objective In this study, we aimed to translate and revise the Summary of Diabetes Self-Care Activities( SDSCA) and the Confidence In Diabetes Self-care( CIDS) scales, to test the reliability and validity of the two scales in Chinese adult type 1 diabetes( T1D) patients. Methods In the first step, Chinese versions( C-SDSCA and C-CIDS) were developed conceptually equivalent to the English versions. And the investigation was conducted in 100 patients from Guangdong T1D Translational Medicine Study. 15 of them were randomly chosen to be retested 4 weeks later. Cronbach's α were used to assess reliability, and factor analysis to its validity. The relationship between scores of C-SDSCA and C-CIDS were analyzed using Spearman correlation analysis. Results The overall Cronbach's α of C-SDSCA was 0.72 and the retest reliability was 0.95( sub-scale:0.67-1.00) . 4 common factors were extracted by factor analysis, and the cumulative contribution was 87.39％. As for C-CIDS, the general Cronbach's α was 0.84 and the retest reliability was 0. 70 ( sub-scale: 0. 49-0. 86 ) . 6 common factors were extracted and the cumulative contribution was 75.41％. The score of the two scales was positively related(r=0.61, P<0.01). Conclusion The revised C-CIDS and C-SDSCA scales turn out to have good reliability and validity, and can be used as instruments to assess diabetes self-management efficacy and self-care activities of Chinese adult T1D patients.

Decreased β-Cell Function is Associated with Cardiovascular Autonomic Neuropathy in Chinese Patients Newly Diagnosed with Type 2 Diabetes / 神经科学通报·英文版

The influence of β-cell function on cardiovascular autonomic neuropathy (CAN), an important diabetes-related complication, is still unclear. In this study, we aimed to investigate the association between residual β-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN+ group (diabetic patients with CAN, n = 20) and a CAN- group (diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured. Homeostasis model assessment-beta cells (HOMA-B) and HOMA-insulin resistance (IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN- group, the CAN+ group had significantly lower fasting plasma insulin (6.60 ± 4.39 vs 10.45 ± 7.82 μ/L, P = 0.029), fasting C-peptide (0.51 ± 0.20 vs 0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B (21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio (r = 0.24, P = 0.043) and the 30:15 test (r = 0.26, P = 0.023). Further analysis showed that fasting C-peptide (OR: 0.041, 95% CI 0.003-0.501, P = 0.012) and HOMA-B (OR: 0.965, 95% CI 0.934-0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values < 0.67 nmol/L were more likely to have CAN than those with C-peptide levels ≥0.67 nmol/L (OR: 6.00, 95% CI 1.815-19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased β-cell function was closely associated with CAN in this population.

Effect of GLP-1 receptor agonist on lipolysis in adipose tissue of obese mice and its underlying mechanism / 中国病理生理杂志

AIM:To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on white adipose tissue (WAT) and the underlying mechanisms.METHODS:Male C57BL/6J mice (8 weeks) were chal-lenged by high-fat diet for 12 weeks, and were randomly divided into saline group and exendin-4 group.The mRNA expres-sion of sirtuin 1 (SIRT1), adipose triglyceride lipase (ATGL), TNF-αand adiponectin of WAT was detected by real-time PCR.3T3-L1 adipocytes or mouse embryonic fibroblasts cells were treated with exendin-4 for 24 h.The protein levels of SIRT1, ATGL and hormone-sensitive lipase (HSL) were determined by Western blot.RESULTS:Exendin-4 significantly decreased epididymal fat weight, fasting blood glucose and serum triglyceride levels ( P<0.05) , and reduced body weight and serum TNF-αlevel.The mRNA expression of SIRT1, ATGL and adiponectin in WAT was all significantly up-regulated by exendin-4, which were contrary to the down-regulation of TNF-αmRNA expression (P<0.05).Exendin-4 promoted the protein expression of SIRT1, ATGL, and HSL in 3T3-L1 adipocytes in a dose-dependent manner.Less lipid droplets with up-regulation of lipolytic protein expression were observed when combined with SIRT1 agonist treatment, which were suppressed by SIRT1 inhibitor.Deletion of SIRT1 led to larger adipocytes with more lipid droplets, and the effect of ex-endin-4 on the lipolysis disappeared when SIRT1 was deficient.CONCLUSION:Exendin-4 promotes lipolysis in WAT of obese mice via activation of SIRT1.

Factors affecting mean blood glucose level of newly diagnosed type 2 diabetes pa-tients / 中国病理生理杂志

AIM:TodetecthemoglobinA1c(HbA1c)andparametersofbloodglucosefluctuationinChinesenewlydiag-nosed type 2 diabetes mellitus (T2DM) patients, and further to specify the factors that were related to mean blood glucose (MBG) in this population.METHODS:Newly diagnosed T2DM patients (n=90) from 4 hospitals in Guangdong province were enrolled, and subjected to 3 d continuous glucose monitoring (CGM) after testing for HbA1c and other laboratory tests.Blood glucose data collected during CGM were used to calculate MBG and parameters of blood glucose fluctuation.RESULTS: Correlation analysis revealed that MBG was significantly related to all parameters of blood glucose fluctuation, HbA1c, fast plasma glucose ( FPG) and 2 h postprandial glucose (P<0.01), but not to sex, age or blood lipid profile.Further analysis utilizing step-wise general linear model showed that HbA1c, absolute means of daily difference ( MODD) , difference between maximal and minimal glucose ( DMMG) and FPG had the strongest relation to MBG.CONCLUSION: Factors affecting MBG of the newly diagnosed T2DMpatients in our country include HbA1c, FPG, DMMG and MODD, and thus it may be prone to misleading results that only HbA1c is applied to estimate MBG in this population.

Insulin and gliclazide therapies improve liver lipid deposition in type 2 di-abetic rats / 中国病理生理杂志

AIM:To investigate the effect of insulin and gliclazide therapies on the liver fat accumulation in type 2 diabetic rats .METHODS:A high-fat diet plus low-dose streptozotocin was implemented to establish a type 2 dia-betic rat model, and the rats were randomly divided into diabetes mellitus (DM) group, diabetic rats treated with insulin ( INS) group, diabetic rats treated with gliclazide per os ( PO) group, and normal control ( NC) group.The diabetic rats in INS group and PO group were given insulin and gliclazide for 3 weeks, respectively.The changes of the liver fatty were evaluated with oil red O staining .Fasting plasma adiponectin concentration was measured by ELISA .The expression of adi-ponectin receptor 1 ( AdipoR1 ) was detected by real-time PCR.The protein levels of AMP-activated protein kinase (AMPK), phosphorylated AMPK on threonine 172 ( Thr172p-AMPK), sterol regulatory element-binding protein 1c (SREBP-1c), phosphorylated SREBP-1c on serine 372 (Ser372p-SREBP-1c), acetyl-CoA carboxylase (ACC), phospho-rylated ACC on serine79 (Ser79p-ACC) and immunoglobulin-binding protein (BiP) in the liver homogenate were deter-mined by Western blotting .RESULTS:Compared with the normal rats , in DM group, the presence of cytoplasmic lipid deposits was confirmed by oil red O staining .In INS group, these changes were significantly lower than those in DM group . Similar results were obtained in PO group .Insulin therapy significantly increased the plasma concentration of diponectin and liver tissue levels of AdipoR1 compared with DM group.At the same time, these 2 indicators returned to normal levels after gliclazide therapy .Thr172p-AMPK/AMPK, Ser372p-SREBP-1c/SREBP-1c and Ser79p-ACC/ACC expression ratios were significantly reduced in DM group compared with control values .The expression of BiP was increased on the contrary . After insulin therapy, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c were significantly increased, and Ser79p-ACC/ACC and BiP returned to the normal levels .After gliclazide treatment, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c returned to the normal levels , the expression ratio of Ser79p-ACC/ACC had no significant improve-ment compared with DM group , and the expression of BiP significantly declined .CONCLUSION: Both the insulin and gliclazide therapies reduce the lipid deposition in the liver of rats with type 2 diabetes by activating AMPK , but the extent and mechanism are not the same.In insulin therapy, AMPK restrains the expression of SREBP-1c directly, increases the phosphorylation of SREBP-1c, and affects SREBP-1c by inhibiting the endoplasmic reticulum stress .Gliclazide treatment, which has no effect on the lipid oxidation , reduces lipid deposition in the liver only through the phosphorylation of SREBP-1c and the suppression of the endoplasmic reticulum stress .

The prevalence and risk factors of metabolic syndrome among adult residents in Guangdong and Jiangsu provinces in China / 中华内科杂志

Objective To determine the current prevalence and risk factors of metabolic syndrome (MS) among adult residents in Chinese developed areas.Methods The clinical data of 6614 adult residents,including 4051 women,from Guangdong and Jiangsu provinces from China Diabetes and Metabolic Disorders Study (2007-2008) were analyzed.Age and sex standardized prevalences of MS were calculated according to the criteria of Chinese Diabetes Society (CDS),US National Cholesterol Education Program Adult Treatment Panel Ⅲ (ATP Ⅲ),International Diabetes Federation (IDF) and Joint Interim Statement (JIS),respectively.Logistic regression analysis was performed to identify the risk factors of MS.Results Age and sex standardized prevalences of MS were 17.88％ (CDS),28.50％ (ATP Ⅲ),21.99％ (IDF) and 31.50％ (JIS),respectively.The prevalences of residents with at least one metabolic abnormality were 67.86％ (CDS) 79.56％ (ATP Ⅲ),79.62％ (IDF) and 80.74％ (JIS),respectively.MS was more common in female than in male by the ATPⅢ and IDF criterion (ATPⅢ:30.63％ vs 26.45％,P ＜0.01 ; IDF:26.04％ vs 17.91％,P ＜ 0.01),while the prevalence was higher in male by CDS criteria (15.94％ vs 19.87％,P ＜0.01).There was no significant difference in the MS prevalence between the rural and the urban residents.Kappa test showed ATP Ⅲ and JIS criteria were most homogenous (κ =0.95,P ＜ 0.01).The risk factors for MS by the logistic regression model were male,older age,lower degree of education,family history of hypertension and obesity,drinker as well as uncontrolled diet.Conclusion The prevalence of MS is high in the adult residents of Chinese developed areas (Guangdong and Jiangsu provinces),whatever diagnostic criterion was used.Effective measures should be taken to control the modifiable MS risk factors.

The effects of insulin and gliclazide therapy on endoplasmic reticulum stress and insulin sensitivity in liver of type 2 diabetic rats / 中华内科杂志

Objective To investigate the effect of insulin and gliclazide therapy on endoplasmic reticulum (ER) stress and insulin sensitivity in the liver of type 2 diabetic rats.Methods A high fat diet plus a low-dose of streptozotocin was implemented to create a type 2 diabetic rats which were randomly divided into diabetes mellitus (DM) group,insulin treatment (INS) group and gliclazide treatment (GT)group; and healthy rats were as normal control group.Diabetic rats in INS and GT groups were given neutral protamine hagedorn (NPH) insulin and gliclazide respectively for 3 weeks.Protein expression levels of immunoglobulin binding protein (Bip),spliced X-box binding protein 1 (XBP-ls),phosphorylated c-Jun on serine 73 (p-c-Jun),phosphorylated insulin receptor substrate 1 on serine 307 (p-IRS-1),and glucose-6-phosphatase (G6Pase) in liver homogenate were detected by Western blotting.Results Compared with the normal rats,Bip and XBP-Is in the DM group were up-regulated (0.28 ±0.07 vs 0.90 ±0.10 for Bip;0.41 ± 0.07 vs 0.95 ±0.07 for XBP-1 s; both P ＜ 0.01 ) ; p-c-Jun (0.59 ± 0.18 vs 1.94 ± 0.03 ),p-IRS-1( 1.73 ± 0.18 vs 5.32 ± 0.22) and G6Pase (0.11 ± 0.01 vs 0.45 ± 0.01 ) were increased ( all P values ＜0.01 ).In the INS group,all of aforementioned changes were reversed (0.90 ± 0.10 vs 0.25 ± 0.04 for Bip; 0.95 ±0.07 vs 0.47 ±0.01 for XBP-1s; 1.94 ± 0.03 vs 0.50 ±0.10 for p-c-Jun; 5.32 ± 0.22 vs 1.59 ±0.32 for p-IRS-1 ; 0.45 ±0.01 vs 0.15 ±0.02 for G6Pase,all P values ＜0.01 ).In the GT group,all of aforementioned changes were also attenuated ( 0.90 ± 0.10 vs 0.53 ± 00.02 for Bip ; 0.95 ± 0.07 vs 0.78±0.02 for XBP-1s; 1.94 ±0.03 vs 1.33 ±0.11 for p-c-Jun; 5.32 ±0.22 vs 3.13 ±0.02 for p-IRS-1; 0.45 ± 0.01 vs 0.25 ± 0.01 for G6Pase,all P values ＜ 0.05).Furthermore,all of aforementioned protein levels were down-regulated more obviously in the INS group comparing to the GT group ( all P values ＜ 0.01 ).Conclusions Both insulin and gliclazide therapy could relieve ER stress and e-Jun N-terminal kinase activity and improved insulin sensitivity.The effect of insulin on Bip,XBP-1s,p-c-Jun,p-IRS-1 and G6Pase protein expressions is more obvious than that of glilcazide,which indicates besides lowering glucose,insulin might have protective effects of anti-inflammation,anti-oxidative stress or stimulation of lipid redistribution.

A study of tracking the superparamagnetic iron oxide and enhanced green fluorescent protein labeled miniature porcine bone marrow stem cells by in vitro MRI / 中华内科杂志

Objectives To track bone marrow stem cells (BMSCs) labeled by enhanced green fluorescent protein (EGFP) and superparamagnetic iron oxide ( SPIO ) -poly-L-lysine (PLL) compound by MRI in vitro for autotransplantation into pancreas of type 1 diabetes miniature pigs. Methods The BMSCs were isolated by density gradient centrifugation and attachment culture from type 1 diabetes minipigs' bone marrow. Expressional intensity of EGFP in BMSCs transfected lentivirus-EGFP with a multiplicity of infection Different magnetic resonance scanning protocols were carried out on various density BMSCs labeled by different concentration of SPIO in various time-point in vitro. Results When SPIO concentration was 25mg/L (count in Fe3 + ), the positive Fe3+ -labeling rate of BMSCs was 93. 1%. Most of SPIO particles in BMSCs' cytoplasm were observed in secondary lysosomes, but they were not detected in important organelle as cell nucleus. Comparing with gelatin the MRI of BMSCs labeled with SPIO in the condition with 1 ×104/ml cells density and 25 mg/L Fe3+ concentration in vitro, the signal intensity changes (△SI) after BMSCs labeled with SPIO 3 weeks and 6 weeks in TSE T1WI, TSE T2WI and FLASH T2 * WI sequences were 12%, 41%, 63% and 7%, 28%, 46% respectively (P ＜ 0.01 and P ＜ 0.05, respectively).Conclusions The data showed that the porcine BMSCs labeled with SPIO and EGFP could be traced successfully in vitro by MRI in the suitable sequences.

Epidemiology,Evidence,and Basic Research of Diabetes Mellitus / 中山大学学报(医学科学版)

The prevalence of diabetes is increasing dramatically and what is more serious is that the age of onset of diabetes in population is much younger than that of before.The author has carried out a series of research in diabetes,which mainly focused on epidemiology of diabetes mellitus and molecular genetics,early diagnosis and treatment of type 2 diabetes.This article aims to raise the attention of diabetes and promote the individual diagnosis and therapy of diabetes.

The effects of early intensive therapy on islet beta cell function and long-term glycemia control in newly diagnosed type 2 diabetic patients with different fasting plasma glucose levels / 中华内科杂志

Objective To investigate the effects of early intensive therapy on P cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients with different recruiting fasting plasma glucose (FPG) levels.Methods A total of 382 newly diagnosed type 2 diabetic patients with FPG 7.0-16.7 mmol/L were randomly assigned to therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) or oral hypoglycemic agents (OHA, by using gliclazide and/or metformin) for initial rapid correction of hyperglycemia.The treatments were stopped after euglycemia had been maintained for 2 weeks.The patients were followed longitudinally on diet alone for 1 year.Intravenous glucose tolerances tests (IVCTTs) were performed and blood glucose, insulin and proinsulin were measured before and after therapy as well as at 1-year follow-up.Homeostasis model assessment ( HOMA) of β cell function and insulin resistance index ( HOMA-β and HOMA-IR ) were calculated.All the patients were stratified on the recruiting FPG: stratum A (7.0 mmol/L≤ FPG < 11.1 mmol/L) , stratum B (11.1 mmol/L≤ FPG ≤ 16.7 mmol/L).Results More patients in stratum A achieved target glycemic control (94.4% vs 89.8% ) and in shorter time [(5.9 ±3.8)d vs(6.9 ±3.6)d, P <0.05] as compared with those in stratum B.B cell function represented by HOMA-β and acute insulin response ( AIR) improved significantly after intensive interventions in both stratum A and B patients.However, the remission rate at 1 year was significantly higher in stratum A patients (47.8% ) than those in stratum B (35.7%, P < 0.05).The patients treated with insulin (especially with CSII) had higher remission rates and better improvement of AIR at 1 year follow-up irrespective of the recruiting FPG (CSII or MDI vs OHA: 57.1% , 51.8% vs 32.8% in stratum A, P <0.05; 44.4% , 38.7% vs 18.6% in stratum B, P <0.05).Conclusions Compared with OHA, early short time intensive insulin treatment had more favorable outcomes on maintaining AIR and prolonged glycemic remission in newly diagnosed type 2 diabetic patients irrespective of the recruiting FPG levels.