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Objective:To investigate the effects of insulin glargine administration by jet injection versus conventional insulin pen on glucose profile using professional mode flash glucose monitoring(FGM) system in type 2 diabetic patients with poor glucose control.Methods:In this randomized, controlled, crossover study, 40 patients with T2DM who treated with insulin glargine were enrolled. The patients were randomly divided into group A(jet injector-conventional pen, n=20) and group B(conventional pen-jet injector, n=20). Each patient wore FreeStyle Libre sensor from day 4 to day 17. The specialist nurse instructed patients how to master the injection techniques. Professional FGM system was applied to assess glucose profile. Results:The fasting blood glucose(FBG) of the enrolled patients was(9.37±1.84) mmol/L. In contrast to conventional insulin pen, treatment with the jet injector significantly decreased the 24h MBG [(9.06±2.13 vs 9.98±2.67) mmol/L, P=0.001], MaxBG [(16.69±3.01 vs 17.95±3.48) mmol/L, P=0.001], AUC>10 mmol/L [95.93(21.12, 129.02) vs 142.66( 27.88, 198.46), P=0.002], TAR(31.10±21.89 vs 39.49±25.93, P=0.003), MAGE and SDBG. It was observed that patients using jet injector had significant increased TIR(65.94±20.47 vs 58.32±25.00, P=0.001). There were no difference in the risk of hypoglycaemia between two groups. Conclusion:Insulin jet injector was more effective than the insulin pen on glycaemic control and glucose fluctuation without increasing the risk of hypoglycemia in type 2 diabetic patients with uncontrolled glycemia.
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Objective:To investigate the characteristics of blood glucose fluctuation and risk factors in type 2 diabetic patients with asymptomatic hypoglycemia.Methods:From September 2018 to July 2021, 342 patients with type 2 diabete mellitus who were hospitalized in the Department of Endocrinology of Hefei Hospital Affilitated to Anhui Medical University were enrolled for a retrospective study. The mean amplitude of glycemic excursions(MAGE), coefficient of variation (CV), 24 hour mean blood glucose level (MG), and time in range (TIR) were obtained by continuous glucose monitoring (CGM). According to the results of CGM and whether the patients have hypoglycemia symptoms, they were divided into three groups: no hypoglycemia group, symptomatic hypoglycemia group, and asymptomatic hypoglycemia group. The differences in blood glucose fluctuations were compared among the three groups. Multivariate logistic regression analysis was used to evaluate the risk factors in type 2 diabete mellitus patients with asymptomatic hypoglycemia. The predictive value of MAGE for asymptomatic hypoglycemia was analyzed by receiver operating characteristic (ROC) curve.Results:Compared with the non-hypoglycemia group, the TIR in asymptomatic hypoglycemia group was higher ( Z=-2.042, P=0.041). The asymptomatic hypoglycemia group had lower MG, higher MAGE and CV compared with the other two groups(all P<0.05). Multivariate logistic regression analysis showed that urinary albumin/creatinine ratio (UACR), MAGE, and CV were the risk factors for asymptomatic hypoglycemia, while MG was the protective factor. After adjustment for other risk factors, MAGE was still associated with asymptomatic hypoglycemia ( OR=1.111, 95% CI 0.999-1.235, P=0.049). The sensitivity and specificity of MAGE in predicting asymptomatic hypoglycemia were 0.769 and 0.776, respectively. Conclusions:Patients with asymptomatic hypoglycemia present with larger TIR and MAGE. MAGE, UACR, and CV were risk factors for asymptomatic hypoglycemia. Moreover, MAGE has some predictive value for the occurrence of asymptomatic hypoglycemia.
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Glycemic variability (GV) may be linked to the development of diabetic complications by inducing inflammation, oxidative stress, and endothelial dysfunction. Flash glucose monitoring (FGM) provides a novel method of continuously monitoring interstitial glucose levels for up to 14 days. This study randomly assigned poorly controlled type 2 diabetes mellitus patients treated with metformin and multiple daily injections of insulin (n=60) to either continuous subcutaneous insulin infusion (CSII) treatment or CSII in combination with liraglutide (CSII+Lira) treatment for 14 days during hospitalization. GV was assessed using a FGM system; weight and cardiometabolic biomarkers were also evaluated. The coefficient of variation was significantly reduced in the CSII+Lira group (P<0.001), while no significant change was observed in the CSII group. The changes differed significantly between the two groups in mean amplitude of glycemic excursions (P=0.004), standard deviation (P=0.006), and the percentage of time in the target range (4-10 mmol/L, P=0.005 and >10 mmol/L, P=0.028). The changes in mean of daily differences, interquartile range, and percentage of time in hypoglycemia (<3.3 mmol/L) and hyperglycemia (>13.9 mmol/L) identified by FGM showed no difference. Treatment with liraglutide increased serum adiponectin [33.5 (3.5, 47.7) pg/mL, P=0.003] and heme oxygenase-1 levels [0.4 (-0.0, 1.8) ng/mL, P=0.001] and reduced serum leptin levels [-2.8 (3.9) pg/mL, P<0.001]. Adding the glucagon-like peptide-1 analog liraglutide improved GV, weight, and some cardiometabolic risk markers. The FGM system is, therefore, shown to be a novel and useful method for glucose monitoring.
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Humans , Male , Female , Adult , Middle Aged , Insulin Infusion Systems , Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 2/drug therapy , Liraglutide/administration & dosage , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Pilot Projects , Diabetes Mellitus, Type 2/bloodABSTRACT
ObjectiveThere are few reports on the correlation between blood glucose fluctuation and body mass index(BMI) in patients with type 2 diabetes mellitus (T2DM). This study aims to evaluate the correlation between the two by comparing the differences of glucose fluctuation in T2DM patients with different BMI.MethodsA total of 672 patients with T2DM admitted to the General Hospital of Eastern Theater Command from June 2017 to October 2018 were selected as subjects. They were divided into 4 groups according to the quartile of BMI. The age, height, weight, course of diabetes, hemoglobin, uric acid, glycosylated hemoglobin, HOMA-IR (insulin resistance index) and HOMA-β (islet β cell function index) were collected. The blood glucose of the patients was continuously monitored within 3 days by wearing a continuous glucose monitor (CGMS). The standard deviation of daily blood glucose (SBDG), the mean of daily differences (MODD) and the mean amplitude of glycemic excursion(MAGE) were calculated to analyze the effect of BMI on blood glucose fluctuation.ResultsThe index of blood glucose fluctuation was negatively correlated with BMI, HbA1c and HOMA-β, but positively with HOMA-IR. Compared with the 1st and 2nd quartiles of BMI, the fluctuation level of patients in the 3rd and 4th quartiles was lower. Multivariate logistic regression analysis showed that after adjustment of age, sex, cholesterol, triglyceride and hemoglobin, the risk of hyperglycemia fluctuation in the fourth quartile group was lower than that in the first quartile group (OR=0.594, 95%CI: 1.825~2.062).ConclusionThe fluctuation of blood glucose in patients with higher BMI is lower than that in patients with lower BMI.
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@#Objective To explore the relationship between glycated hemoglobin (HbA1c) level and blood glucose fluctuations after coronary artery bypass grafting (CABG) and adverse events in non-diabetic patients, thus providing theoretical support for intensive preoperative blood glucose management in patients undergoing CABG surgery. Methods A total of 304 patients undergoing CABG with or without valvular surgery from October 2013 to December 2017 were enrolled in this prospective, single-center, observational cohort study. We classified them into two different groups which were a low-level group and a high-level group according to the HbA1c level. There were 102 males and 37 females, aged 36–85 (61.5±9.5) years in the low-level group, and 118 males and 47 females aged 34–85 (63.1±9.4) years in the high-level group. The main results were different in hospital mortality and perioperative complications including in-hospital death, myocardial infarction, sternal incision infection, new stroke, new-onset renal failure and multiple organ failure. To assess the effects of confounding factors, multivariate logistic regression analysis was used. Results Postoperative blood glucose fluctuation was more pronounced in the high-level group than that in the low-level group before admission [0.8 (0.6, 1.2) mmol/L vs. 1.0 (0.8, 1.8) mmol/L, P<0.01]. This study also suggested that the incidence of major adverse events was significantly lower in the low-level group compared with the high-level group (P=0.001). Multivariate logistic regression analyses to correct the influence of other confounding factors showed that HbA1c (OR=2.773, P=0.002) and postoperative blood glucose fluctuations (OR=3.091, P<0.001) could still predict the occurrence of postoperative adverse events. Conclusion HbA1c on admission can effectively predict blood glucose fluctuations in 24 hours after surgery. Secondly, HbA1c on admission and postoperative blood glucose fluctuations can further predict postoperative adverse events. It is suggested that we control the patient's preoperative HbA1c at a low level, which is beneficial to control postoperative blood glucose fluctuation and postoperative adverse events.
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Objective: To compare the effects of different methods on the glucose treat-to-target time, glucose fluctuation, hypoglycemia and insulin doses in the type 2 diabetic patients treated by insulin bump, and to find the best method to make the glucose to reach the standand level safely, fast and effectively in the type 2 diabetic patients treated by insulin bump. Methods; Sixty hospitalized type 2 diabetic patients inadequatly controlled by premix insulin treatment were randomly divided into convention group (n=20), Bolus Wizard group (n=20), and Bolus Wizard combined with monitoring (combination) group (n-20) according to the random number grouping method. The insulin doses of the patients in convention group were adjusted according to the glucose monitoring of fingertip and the doctor' s experiences; the insulin doses of the patients in Bolus Wizard group were adjusted according to the Bolus Wizard software in insulin bump, and the glucose monitoring of fingertip; the insulin doses of the patients in combination group were adjusted according to the Bolus Wizard software combined with real time continuous glucose monitoring system (RTCGM). The level of fingertip glucose was tested. The standard deviation of blood glucose (SDBG) and largest amplitude of glycemic excursion (LAGE) were used to evaluate the glucose fluctuation of the patients in various groups. The treat-to-target time, glucose fluctuation, hypoglycemia and daily insulin doses of the patients in various groups were recorded. Results: Compared with convention group, the treat-to-target time of the patients in Bolus Wizard group was decreased (t= 2. 30, P<0. 05); compared with Bolus Wizard group, the treat-to-target time of the patients in combination group was decreased (t=3. 50, P< 0.05). On the 3rd day of treatment, compared with convention group, the SDBG and LAGE of the patients in Bolus Wizard group were decreased (tSDBC; = 3. 11, tLAGE = 2.54, P<0.05); compared with Bolus Wizard group, the LAGE of the patients in combination group was decreased (tlage = 2. 47, P<0. 05). There were no significant differences in the incidence of total hypoglycemia events (χ2 = 2. 192, P=0. 532), significant hypoglycemia events (χ2= 2.765, P=0. 322) and nocturnal hypoglycemia events (χ2 = 2.192, P=0. 532) among the patients in various groups; there were no significant differences in the average insulin dosage (F= 2. 102, P=0. 131), the non-basic insulin dosage (χ2 = 2.328, P=0. 107) and the percentage of non-basic insulin (χ2= 2.104, P=0. 131) among the patients in various groups. Conclusion: Bolus Wizard software combined with real-time dynamic RTCGM has better effect in the treatment of type 2 diabetes without increasing the risk of hypoglycemia and insulin dosage.
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Objective To observe the influence of glucose fluctuation on paraoxonase-3(PON3) and apoprotein A1(ApoA1) in T2DM patients with coronary heart disease (CHD) . Methods A total of 260 subjects were enrolled in this study and dividied into three groups :T2DM patients with CHD (T2DM +CHD group ,n=100) ,T2DM without CHD (T2DM group ,n=80) and healthy subjects(NC group ,n=80) .The serum PON3 and ApoA1 levels were measured and compared in all the three groups .The 72 h dynamic glucose monitoring (CGMS ) was adopted in T2DM + CHD group ,then according to the MAGE levels ,T2DM+ CHD group was subdivided intotertiles :the lowest tertile subgroup (2.43～3.44 mmol/L ,n=31) ,the middle tertile subgroup (3.45～4.46 mmol/L ,n=39) and the highest tertile subgroup (4.47～5.45 mmol/L ,n= 30) .Influencing factors for PON3 and ApoA1 were analyzed by multivariate linear regression analysis . Results (1)The SBP ,DBP ,FPG ,2 hPG ,HbA1c ,FIns ,ApoB ,BUN ,HOMA-IR , ApoA1 and number of smokers were higher in T2DM + CHD group than in NC group .FPG ,2 hPG ,HbA1c ,FIns and HOMA-IR were higher in T2DM+ CHD group than in T2DM group(P<0.05 or P<0.01) .LDL-C ,Lp-a and hsC-RP were higher ,and the PON3 were lower in T2DM +CHD group than in T2DM group and NC group (P< 0.05 or P< 0.01);(2)With the increase of blood glucose fluctuation range ,the levels of PON3[(0.58 ± 0.10) vs (0.44 ± 0.07) vs (0.25 ± 0.01) ng/ml]and ApoA1 [(2.33 ± 1.04) vs (2.31 ± 0.71) vs(1.05 ± 0.48)g/L]were reduced(all P=0.000);(3)Multiple linear regression analysis showed that BMI ,hsC-RP ,HOMA-IR and MAGE were influencing factors for PON3. And HbA1c ,hsC-RP and MAGE were influencing factors for ApoA1 (P<0.05 or P<0.01) . Conclusion Serum PON3 level is lower and ApoA1 level is higher in T2DM patients with CHD .Glucose fluctuation may be only an influencing factor for ApoA1 level .
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Objective To analyze the present situation of glucose metabolism and the characteristics of blood glucose fluctuation in in-hospital type l diabetic patients (T1DM). Methods One hundred and forty-three hospitalized cases of T1DM patients from November 2012 to November 2016 were retrospectively analyzed.The percentage of adult-onset T1DM patients was 76.22%(109/143)and none adult-onset was 23.78%(34/143). The following data were collected: general information, the indexes of glucose metabolism and islet function.Seventy-two-hour continuous glucose monitoring(CGM) was carried on 40 patients as a subgroup.Results The average age was(40.29 ± 16.79)years.The onset age of diabetes was(33.57 ± 17.18)years.The disease duration was 4.0(1.0,10.0)years.The body mass index(BMI)was(20.68 ± 2.95)kg/m2.The fasting blood glucose(FBG)was(12.02 ± 5.40)mmol/L.The HbA1c was(9.80 ± 2.65)%.The fasting C-peptide was 0.08(0.01,0.38)nmol/L.The 2-hour postprandial C-peptide (C-P 2 h) was 0.12(0.01, 0.70) nmol/L. The anti-glutamic acid decarboxylase antibody was 12.08(8.16,20.56)μg/L.The islet-cell antibody was 4.85(2.66,12.07)μg/L.By using multivariate linear regression analysis, HbA1c were negatively related to the duration and BMI of T1DM. CGM: the mean blood glucose was (10.34 ± 2.97) mmol/L. The standard deviation of blood glucose was (2.89 ± 1.07) mmol/L. The mean amplitude glycemic excursions was (7.10 ± 3.09) mmol/L. The incidence of hypoglycemia was 10.00% (≤ 2.8 mmol/L) and 32.50% (≤ 3.9 mmol/L). Conclusions Adult-onset T1DM patients account for more than two-thirds. In-hospital T1DM patients have poor control of blood glucose, and they show the clinical characteristics of high blood glucose fluctuation and more hypoglycemia.
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Objective To figure out the status of blood glucose fluctuations in patients with type 2 diabetes mellitus(T2DM)and explore its influencing factors. Methods A total of 105 T2DM cases were subjected to multiple surveys with questionnaires pertaining to general patient information,diabetes self-management,medical responses and social support as well as rating scales for the Pittsburg Sleep Quality Index and positive and negative emotions.Furthermore,the continuous glucose monitoring system(CGMS, Medtronic) was used to examine their blood sugar dynamics. Results The outcome of dynamic blood sugar monitoring showed,the standard deviation of blood glucose(SDBG)concentration was(2.41±0.91) mmol/L,the mean amplitude of glycemic excursion(MAGE)per day was(4.01±1.86)mmol/L,the median of glycemic excursion (LAGE)was 5.3 mmol/L,the median of the M-value was 5.13 mmol/L,the median for the means of daily difference(MODD)was 1.84 mmol/L and the median for low blood glucose indexes (LBMI)was 1.08 mmol/L. According to the results derived from multiple stepwise regression analyses, which used blood sugar fluctuation parameters as the variances. The results showed that: annual family income,glycosylated hemoglobin A1c(HbA1c),and diabetes self-management were shown to account for 51.5% of total SDBG variations;HbA1c,diabetes self-management,annual family income,social support and obedience could account for 76.3% of total MAGE variations;HbA1c,negative emotions and annual family income could account for 63.8% of total LAGE variations;HbA1c,annual family income,diabetes self-management and educational status could account for 52.3% of total M-value variations; HbA1c, negative emotions, diabetes self-management, annual family income and sleep quality could account for 48.0% of total MODD variations; HbA1c, annual family income and gender could account for 20.4% of total LBMI variation. Conclusions The T2DM patients, by contrast, demonstrated greater blood sugar fluctuations. HbA1c, annual family income, diabetes self-management, sleep quality, negative emotions and obedience were the main determinants that affect such fluctuations.
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Objective To investigation the influence of diabetes-specific enteral nutrition on stress-induced blood glucose fluctuations and clinical outcomes in septic patients receiving mechanical ventilation.Methods This randomized controlled study included 76 septic patients using mechanical ventilation,who were randomized to a diabetes-specific enteral nutrition group(n=38)and a control group(n=38).Both groups received identical blood glucose control therapy,and blood glucose levels were monitored during the first 72 hours.Blood glucose concentration at admission(BGadm),mean blood glucose level (MBG),blood glucose standard deviation(BGSD),largest amplitude of blood glucose excursion(LABGE),glycemic lability index(GLI),and total dose of intravenous insulin for the two groups were compared.The duration of mechanical ventilation,the length of respiratory intensive care unit (RICU) stay,28-day mortality,the rate of hematogenous infection,and feeding intolerance(FI) were also compared.Results (1) BGSD (mmol/L),GLI,and the total dose of intravenous insulin were significantly lower in the diabetes-specific enteral nutrition group than in the control group (BGSD:1.99±0.99 vs.2.36 ± 1.24;GLI:31.2±17.6 vs.47.8 ± 23.6;the total dose of intravenous insulin:70.3 ± 12.3 vs.77.3 ± 12.6,respectively;t =2.356,4.512,-2.695,all P ＜ 0.05).(2) The duration of mechanical ventilation (9.8 ± 4.6) d,the length of RICU stay (16.2 ± 6.5) d,and 28-day mortality(15.7 ％)in the diabetes-specific enteral nutrition group were significantly lower than in the control group(12.6±2.7)d,(23.4±8.5)d,46.4％,respectively) (t =-4.361,4.664,x2 =4.343,all P＜0.05);the rate of hematogenous infection(5.3％)and FI(7.9％)were significantly lower in the diabetes-specific enteral nutrition group than in the control group (21.1％,28.9 ％,P ＜ 0.05).Conclusions Diabetes-specific enteral nutrition can help reduce stress-induced blood glucose fluctuations and improve the clinical outcomes of septic patients receiving mechanical ventilation.
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Objective To learn the injury severity and the possible mechanism of the thyroid tissue of DM rats with different levels of glucose levels. Methods Firstly,20 Wistar rats were treated with STZ to create the experimental diabetic rats models. Then,the DM rats were divided into two groups including the persistence hyperglycemia group(n = 10),and blood glucose fluctuation group(n = 10). Another 10 Wistar rats were treated as the control group. Rats were sacrificed after 12 week treatment. The bilateral thyroid were weighted and the blood biochemistry tests were conducted for detecting glucose level,lipid levels,and thyroid functions. The ultra - structure of thyroid tissue was observed using electron microscope. Results The MBG,LAGE,and SDBG of blood glucose fluctuation group and the persistence hyperglycemia group were all higher than the control group(P ﹤ 0. 05). The MBG of blood glucose fluctuation group were lower than the persistence hyperglycemia group(P ﹤ 0. 05),the SDBG and LAGE were higher than the persistence hyperglycemia group(P ﹤ 0. 05). The TC,FPG,and HbA1c levels of DM rats were significantly higher in blood glucose fluctuation group than in control group(P ﹤ 0. 05). TC ,FPG and TG levels of the DM rats in blood glucose fluctuation group were significantly lower than the rats in persistence hyperglycemia group(P ﹤ 0. 05). No significance of the free T3 and free T4 levels was observed between the diabetes rats in persistence hyperglycemia group and blood glucose fluctuation group. However,the free T3 and T4 levels were significantly lower in both model groups than in control group(P ﹤ 0. 05). The injury of follicular epithelial cells and loss of microvilli were observed in diabetes rats in both the hyperglycemia group and blood glucose fluctuation group. Conclusion The ultra - structure changes of thyroid gland tissues indicated that abnormal glucose and lipid metabolism could result in thyroid gland tissue injury,which is the potential mechanism. However,no difference of the thyroid function and ultra - structure were observed between the hyperglycemia group and blood glucose fluctuation group.
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Diabetes mellitus is a common metabolic disease and poses serious threat to human health. Diabetic complications are the major causes of both morality and disability. In recent years, studies show that the glucose fluctuation plays an important role in the development of chronic diabetic complications. As a new discipline to identify the overall metabolic changes of living organisms, metabolomics provides new insights into the study of diabetes and diabetic complications. In this paper, the recent studies on the development of chronic diabetic complications and blood glucose fluctuation in the field of metabolomics were reviewed.
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Objective To investigate the influence of blood glucose fluctuation on ser202 phosphorylation sites of tau protein( p-Tau) in hippocampus of diabetic rats; to explore the possible mechanism of blood glucose fluctuation impacting on tau protein hyperphosphorylation. Methods Healthy male Sprague Dawley rats were randomly divided into normal control group ( NC group ) and diabetes group. After diabetic rats model was established, all the diabetic rats were randomly divided into diabetic continuous hyperglycemia group (DC group) and diabetic blood glucose fluctuant group ( DF group). Rats in DF group were given glucose solution intraperitoneal injection twice at regular time everyday. 30 minutes after each intraperitoneal injection, insulin subcutaneously injections were given. Rats in the NC group and DC groups were given the same volume of saline subcutaneous injection. Specimens were collected in 8 weeks, the levels of p-Tau and total tau in rat hippocampus were detected by immunohistochemical staining and Western blotting. The immunoreactive positive products were analyzed by image analysis system. Glycogen synthase kinase-3β(GSK-3β) mRNA was detected by realtime PCR. Results (1) Blood glucose fluctuation of rats in DC and DF group were greater than NC group. And the mean blood glucose, standard deviation of mean blood glucose (SDBG), and large amplitude of glycemic excursion (LAGE) levels were increased significantly compared to NC group, the difference has statistical significance ( all P < 0. 05). Compared with DC group, SDBG and LAGE levels of DF group were higher (both P<0. 05). HbA1C and insulin levels were no difference (P>0. 05). (2) Compared with NC group, the hippocampal p-Tau level of DC group and DF group were increased (P < 0. 05 ); Compared with DC group, the hippocampal p-Tau expression of DF group was increased ( P <0. 05). Compared with DC group, a higher hippocampal GSK-3β mRNA level was found in DF group ( P <0. 05). Conclusions On the basis of diabetes animal model, giving glucose solution intraperitoneal injection and insulin subcutaneously injection 30 minutes later twice at regular time everyday could establish experimental model of diabetic blood glucose fluctuation. Blood glucose fluctuation may aggravate the diabetic rats hippocampal p-Tau. The possible mechanism seems to be an up regulation of the GSK-3β.
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Objective To investigate the influence of blood glucose fluctuation on ser202 phosphorylation sites of tau protein( p-Tau) in hippocampus of diabetic rats; to explore the possible mechanism of blood glucose fluctuation impacting on tau protein hyperphosphorylation. Methods Healthy male Sprague Dawley rats were randomly divided into normal control group ( NC group ) and diabetes group. After diabetic rats model was established, all the diabetic rats were randomly divided into diabetic continuous hyperglycemia group (DC group) and diabetic blood glucose fluctuant group ( DF group). Rats in DF group were given glucose solution intraperitoneal injection twice at regular time everyday. 30 minutes after each intraperitoneal injection, insulin subcutaneously injections were given. Rats in the NC group and DC groups were given the same volume of saline subcutaneous injection. Specimens were collected in 8 weeks, the levels of p-Tau and total tau in rat hippocampus were detected by immunohistochemical staining and Western blotting. The immunoreactive positive products were analyzed by image analysis system. Glycogen synthase kinase-3β(GSK-3β) mRNA was detected by realtime PCR. Results (1) Blood glucose fluctuation of rats in DC and DF group were greater than NC group. And the mean blood glucose, standard deviation of mean blood glucose (SDBG), and large amplitude of glycemic excursion (LAGE) levels were increased significantly compared to NC group, the difference has statistical significance ( all P < 0. 05). Compared with DC group, SDBG and LAGE levels of DF group were higher (both P<0. 05). HbA1C and insulin levels were no difference (P>0. 05). (2) Compared with NC group, the hippocampal p-Tau level of DC group and DF group were increased (P < 0. 05 ); Compared with DC group, the hippocampal p-Tau expression of DF group was increased ( P <0. 05). Compared with DC group, a higher hippocampal GSK-3β mRNA level was found in DF group ( P <0. 05). Conclusions On the basis of diabetes animal model, giving glucose solution intraperitoneal injection and insulin subcutaneously injection 30 minutes later twice at regular time everyday could establish experimental model of diabetic blood glucose fluctuation. Blood glucose fluctuation may aggravate the diabetic rats hippocampal p-Tau. The possible mechanism seems to be an up regulation of the GSK-3β.
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[Summary] A total of 128 individuals with type 2 diabetes underwent continuous glucose monitoring for 3 consecutive days.The dawn phenomenon was defined by three different parameters according to the previous research:(1)the absolute increase of glucose level from nocturnal nadir to prebreakfast value(?G) above 20 mg/dl;(2)?G above 10 mg/dl;( 3 ) insulin requirement increased at least 20%.The participants were secondarily separated by presence/absence of a dawn phenomenon based on the definitions above.The impact on blood glucose fluctuation of different groups was assessed according to the standard deviation of blood glucose( SDBG) , the area under curve above 10 mmol/L ( AUC ) , and the mean amplitude of glycemic excursions ( MAGE ) , etc.The frequencies of dawn phenomenon were 64.8%(?G≥20mg/dl), 85.2%(?G≥10 mg/dl), and 59.4%(rise in insulin requirement≥20%)respectively.The impacts on SDBG, AUC, MAGE, and MODD were without statistical difference(P>0.05) between the presence and absence of the dawn phenomenon patients when?G≥10 mg/dl.However, the differences reached statistical significance(P<0.05) when ?G≥20 mg/dl and the increase in insulin requirement≥20%. Besides, the incidence of dawn phenomenon was positively correlated with HOMA-IR, HbA1C , and free C-peptide.Dawn phenomenon is a very frequent event in type 2 diabetes and not only impacts the overall glycemic control but also exaggerates glucose fluctuation.To be clinically relevant, ?G≥20mg/dl should be taken as the quantitative criterion of the dawn phenomenon.
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Objective Oxidative stress which participates in the development of diabetes and its complications can induce inflammation and increase the damage and apoptosis on cells and tissue by influencing multiple signaling pathways?Blood glucose fluctuation increased oxidative stress and aggravated damage and apoptosis on cells?The roles of glucagon?like peptide?1 ( GLP?1) receptor agonist can improve blood glucose fluctuation by playing multiple system physiological effects,such as,delaying gastric emptying,reducing appetite, food intake and body weight, enhancing glucose dependent insulin secretion, inhibiting glucose dependent glucagon secretion?In addition,GLP?1 can reduce oxidative stress state by reducing the reactive oxygen species, inhibiting oxidase activity,up?regulating anti?oxidative stress genes,increasing the level of antioxidant enzymes.
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Objective: To observe the protective effect of salvianolic acid B (Sal B) on pancreatic islet cells in diabetic rats with fluctuating blood glucose and the possible mechanisms implicated. Methods: Diabetes model in rats was established by feeding with high-sugar and high-fat diets combined with ip injection of streptozotocin (STZ). Then the rats were subjected to ip injection of insulin and/or ig administration of glucose at indicated time for 6 weeks to induce blood glucose fluctuation, with those in Sal B groups ig supplemented with Sal B 160 or 80 mg/kg. The contents of fasting blood glucose (FBG), fasting serum insulin (FINS), and glycosylated hemoglobin (GHb) and the levels of total anti-oxidant capacity (TAC), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) in both serum and pancreatic tissues were determined with commercially available kits. Pathological changes and cell apoptosis in pancreatic islets were evaluated by HE staining and TUNEL staining, respectively. Protein levels of PDX-1 in pancreatic tissues were examined by Western blotting analysis. Results: Compared with the control group, the contents of FBG, GHb, and MDA in diabetic rats were increased significantly, while the levels of FINS, TAC, and SOD activity were decreased markedly (P < 0.01). Pancreatic islets in diabetic rats became decreased in size and number, while cell apoptosis in islets increased notably (P < 0.01). Protein level of PDX-1 was significantly decreased in pancreas of diabetic rats (P < 0.01). Supplementation with Sal B resulted in a significant decrease in FBG, GHb, and MDA contents and increase in FINS, TAC, and SOD activity in diabetic rats (P < 0.05, 0.01). Sal B significantly attenuated pathological changes and reduced cell apoptosis in pancreatic islets of diabetic rats, with the expression of PDX-1 protein up-regulated evidently (P < 0.05 or 0.01). Conclusion: Sal B can significantly ameliorate pancreatic pathological changes and improve pancreatic islet function in diabetic rats with fluctuating blood glucose, which might be attributed to attenuation of oxidative stress, up-regulation of PDX-1 expression, and suppression of islet cell apoptosis.
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[ ABSTRACT] AIM:To investigate whether the increase in PTEN expression is related to apoptosis, and whether it is regulated by reactive oxygen species( ROS) .METHODS: The rat islet cells were divided into constant low glucose group ( group L) , constant high glucose group ( group H) , glucose fluctuation group ( group F) , low glucose after high glucose group (group HL) and low glucose after fluctuation group (group FL).The ROS level, apoptotic rate, intracellu-lar calcium, insulin release and PTEN protein expression were analyzed.RESULTS:Compared with groups H and L, the insulin secretion decreased, and intracellular calcium, ROS level, PTEN protein expression and apoptotic rate increased in group F ( P<0.05) .Compared with group H, the intracellular calcium, ROS level, PTEN protein expression and apoptot-ic rate in group HL decreased, but were still higher than those in group L (P<0.05).Compared with group F, the intra-cellular calcium, ROS level, PTEN protein expression and apoptotic rate in group FL decreased, but were still higher than those in group L (P<0.05).CONCLUSION:Glucose fluctuation can cause the apoptosis of islet cells more easily than constant high glucose.This may be related to the change of intracellular calcium and increase in oxidative stress which pro-motes PTEN expression.The recovery of glucose level to some extent relieves oxidative stress, decrease PTEN expression and reduce cell damage.
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Objective: To observe the effect of Yuquan Pill on the blood glucose fluctuation of diabetic patients receiving insulin therapy with the deficiency type of qi and yin. Methods: One hundred and six patients in Nanjing city hospital of traditional Chinese medicine from January 2012 to August 2014, with the diabetes mellitus in the view of Western medicine and with deficiency of both qi and yin diagnosis standard according to the theory of traditional Chinese medicine (TCM), were selected and randomly divided into treatment group and control group. The original insulin therapy of all subjects continues. The patients in treatment group were given Yuquan Pill, once daily. The patients in control group were not treated by Chinese materia medica, but kept corresponding follow-up. The course of treatment was 28 d. These indicators were to assess at the beginning and end of the research, including the mean blood glucose level (MBG), duration below low limit (DBLL), standard deviation of blood glucose (SDBG), largest amplitude glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE), and means of daily differencies (MODD). Results: In the treatment group, dry mouth and throat, fatigue, eat easy to hunger, shortness of breath, sweating, palpitation, cardiac heat, syndrome integral treatment of insomnia, and tongue were improved significantly compared with before the treatment (P < 0.05); The two groups after treatment, TCM syndromes of throat dry, feverish feeling in palms and soles, sweating, palpitations, insomnia, and tongue coating were better improved significantly in the treatment than those in the control group (P < 0.05). The MAGE of the patients in the treatment group decreased after the treatment compared with those before treatment (P < 0.05). The MAGE level was decreased apparently compared with the control group. Conclusion: This study shows that the fluctuation of blood glucose levels in diabetic patients receiving insulin therapy with the deficiency type of qi and yin can be improved by the treatment of Yuquan Pill.
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[ ABSTRACT] AIM:To explore the mechanisms of fluctuant high blood glucose-induced apoptosis of hepatocytes. METHODS:SD rats were randomly divided into normal control group ( N) , stable high blood glucose group ( S) , fluctu-ant high blood glucose group ( F) and insulin group ( I) .Diabetic rats were induced by intraperitoneal injection of strepto-zotocin (65 mg/kg) , and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time points every day.The blood glucose fluctuation patterns of the animals in F group with-in 12 weeks were similar every day and no significant difference of the HbA1c concentration was observed compared with S group, indicating that the fluctuant hyperglycemia was successfully established in F group.The activity of superoxide dis-mutase ( SOD) and glutathione peroxidase ( GSH-Px) , and the content of malondialdehyde ( MDA) and nitric oxide ( NO) in the homogenate of the liver tissues were detected by colorimetry.The mRNA and protein levels of JNK, p-JNK, Bax and Bcl-2 were examined by RT-PCR and Western blot.RESULTS:After 12 weeks, the increases in the intakes of food and water, the urine output, and the abnormal liver function were observed in S group, I group and F group.Compared with N group, the MDA level was increased, the content of NO and the activity of SOD and GSH-Px were decreased, and up-regu-lation of JNK mRNA and p-JNK and Bax proteins, and down-regulation of Bcl-2 were also found in S group, I group and F group.The above effects were more obviously showed in F group.CONCLUSION:Oxidative stress activates JNK-MAPK signaling pathway, which is involved in fluctuant high glucose-induced apoptosis of hepatocytes.