Xiao-fei Su

Blood Glucose Fluctuations in Type 2 Diabetes Patients Treated with Multiple Daily Injections

To compare blood glucose fluctuations in type 2 diabetes mellitus (T2DM) patients were treated using three procedures: insulin intensive therapy which is continuous subcutaneous insulin infusion (CSII), MDI3 (three injections daily), and MDI4 (four injections daily). T2DM patients were hospitalized and were randomly assigned to CSII, aspart 30-based MDI3, and glargine based MDI4. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. After completing the baseline assessment, 6-day continuous glucose monitoring (CGM) was performed before and after completion of insulin treatment. Treatment with CSII provided a greater improvement of blood glucose fluctuations than MDI (MDI3 or MDI4) therapy either in newly diagnosed or in long-standing T2DM patients. In long-standing diabetes patients, the MDI4 treatment group had significantly greater improvement of mean amplitude glycemic excursion (MAGE) than the MDI3 treatment group. However, in patients with newly diagnosed diabetes, there were no significant differences in the improvement of MAGE between MDI3 and MDI4 groups. Glargine based MDI4 therapy provided better glucose fluctuations than aspart 30-based MDI3 therapy, especially in long-standing T2DM patients, if CSII therapy was not available.

Influence of Acarbose on Plasma Glucose Fluctuations in Insulin-Treated Patients with Type 2 Diabetes: A Pilot Study

Background and Aims. To evaluate the effect of adding acarbose on glycemic excursions measured by continuous glucose monitoring system (CGMS) in patients with type 2 diabetes mellitus (T2DM) already on insulin therapy. Materials and Methods. This was an opened and unblended study. 134 patients with T2DM were recruited. After initial rapidly corrected hyperglycaemia by continuous subcutaneous insulin infusion (CSII) for 7 d, a 4–6-day premixed insulin titration period subsequently followed. Patients were then randomized 1 : 1 to acarbose plus insulin group or insulin therapy group for 2 weeks. CGMS was used to measure glucose fluctuations for at least 3 days after therapy cessation. Results. Patients in acarbose plus insulin group achieved a significant improvement of MAGE compared to that of insulin therapy only group (5.56 ± 2.16 versus 7.50 ± 3.28 mmol/L, P = 0.044), accompanied by a significant decrease in the incremental AUC of plasma glucose concentration above 10.0 mmol/L (0.5 [0.03, 0.9] versus 0.85 [0.23,1.4]  mmol/L per day, P = 0.037). Conclusions. Add-on acarbose to insulin therapy further improves glucose fluctuation in patients with T2DM. This study was registered with ClinicalTrials.gov registration number ChiCTR-TRC-11001218.

Influence of Dapagliflozin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Objectives. To observe changes in blood glycemic variations and oxidative stress level before and after dapagliflozin treatment in patients with newly diagnosed T2DM. Methods. This was a randomized, double-blind, placebo-controlled, phase 3 trial. A total of 28 patients with newly diagnosed T2DM with HbA1c levels of 7.5–10.5% were randomly selected to receive dapagliflozin or placebo treatment for 24 weeks. After baseline data were collected, we analyzed glycemic variations and plasma 8-iso PGF2α level at baseline and at the endpoint. Primary outcome was the changes of mean amplitude glycemic excursion (MAGE) within groups. Results. After 24-week dapagliflozin therapy, our data showed the significant improvement of MAGE with dapagliflozin therapy (P = 0.010). Compared with control group, patients in dapagliflozin group exhibited reduction in 24-hour MBG (P = 0.026) and lower mean plasma glucose concentrations, especially during periods from 2400 to 0200 and 1300 to 1800 (P < 0.05, resp.). In addition, plasma 8-iso PGF2α level was notably decreased in the treatment group compared to the control group (P = 0.034). Conclusions. In conclusion, this study shows the ability of dapagliflozin to improve glycemic variations and associate with reduction of oxidative stress in patients with T2DM, which may benefit the cardiovascular system.

Features of glycemic variations in drug naïve type 2 diabetic patients with different HbA 1c values

To define the features of glycemic variations in drug naïve type 2 diabetic (T2D) patients with different HbA1c values using continuous glucose monitoring (CGM), a total of 195 drug naïve T2D patients were admitted. The subjects were divided into the following groups: lower HbA1c values (≤8%), moderate HbA1c values (>8% and ≤10%), and higher HbA1c values (>10%). The patients underwent oral glucose tolerance tests and were then subjected to 3-day CGM. The primary endpoint was the differences in the 24-hr mean amplitude of glycemic excursions (MAGE) in patients with different HbA1c values. Patients with higher HbA1c values had larger MAGEs than those in the moderate and lower groups (7.44 ± 3.00 vs. 6.30 ± 2.38, P < 0.05, 7.44 ± 3.00 vs. 5.20 ± 2.35, P < 0.01, respectively). The 24-hr mean glucose concentrations increased incrementally in the patients with lower, moderate and higher HbA1c values. Moreover, the patients with higher HbA1c values exhibited higher peak glucose concentrations and prolongation in the time to peak glucose. Patients with higher HbA1c values had larger MAGE compared with those with lower and moderate HbA1c values. Our data indicated patients with higher HbA1c values should receive special therapy aimed at reducing the larger glycemic variations.

Effects of saxagliptin add-on therapy to insulin on blood glycemic fluctuations in patients with type 2 diabetes: A randomized, control, open-labeled trial.

Background: To investigate whether saxagliptin add-on therapy to continuous subcutaneous insulin infusion (CSII) further improve blood glycemic control than CSII therapy in patients with newly diagnosed type 2 diabetes (T2D). Methods: This was a single-center, randomized, control, open-labeled trial. Newly diagnosed T2D patients were recruited between February 2014 and December 2015. Subjects were divided into saxagliptin add-on therapy to CSII group (n = 31) and CSII therapy group (n = 38). The treatment was maintained for 4 weeks. Oral glucose tolerance test was performed at baseline. Serum samples were obtained before and 30 and 120 minutes after oral administration for glucose, insulin, and C-peptide determination. Continuous glucose monitoring (CGM) was performed before and endpoint. Results: A total of 69 subjects were admitted. After 4-week therapy, CGM data showed that patients with saxagliptin add-on therapy exhibited further improvement of mean amplitude glycemic excursion (MAGE), the incremental area under curve of plasma glucose >7.8 and 10 mmol/L compared with that of control group. In addition, the hourly mean blood glucose concentrations, especially between 0000 and 0600 in patient with saxagliptin add-on therapy, were significantly lower compared with that of the control patients. Furthermore, patients in saxagliptin add-on group needed lower insulin dose to maintain euglycemic control. In addition, severe hypoglycemic episode was not observed from any group. Conclusion: Saxagliptin add-on therapy to insulin had the ability of further improve blood glycemic controlling, with lower insulin dose required by patients with T2D to maintain euglycemic controlling.

Young onset type 2 diabetic patients might be more sensitive to metformin compared to late onset type 2 diabetic patients

It is unknown whether YOD (young onset diabetes) and LOD (late onset diabetes) require similar insulin doses for intensive insulin therapy with a metformin add-on to achieve glycemic control. We analyzed data from our two previously performed randomized, controlled open-label trials. Patients were randomized to receive either continuous subcutaneous insulin infusion (CSII) therapy or CSII combined with metformin therapy for 4 weeks. The studies concentrated on the differences in the insulin doses used for the two groups. We included 36 YOD (age < 40 yrs) and 152 LOD (age > 40 yrs) patients. YOD patients who received metformin combined with CSII therapy required significantly lower insulin doses to maintain euglycemic control compared to patients with LOD. A multivariate analysis, controlled for gender and the fasting blood concentration, was performed to determine the significance of the differences between groups, particularly with respect to the total and basal insulin doses. There was a trend toward improvement in β-cell function and insulin resistance in terms of ΔHOMA-B and ΔHOMA-IR in patients with YOD compared to those with LOD. Newly diagnosed T2D patients with YOD required significantly lower insulin doses, particularly basal insulin doses, to maintain glycemic control compared to the LOD patients.

Association of lower body mass index with increased glycemic variability in patients with newly diagnosed type 2 diabetes: a cross-sectional study in China

Previous studies have indicated that the pathogenesis of diabetes differs between obese and lean patients. We investigated whether newly diagnosed Chinese diabetic patients with different body mass indices (BMIs) have different glycemic variability, and we assessed the relationship between BMI and glycemic variability. This was a cross-sectional study that included 169 newly diagnosed and drug-naïve type 2 diabetic patients (mean age, 51.33 ± 9.83 years; 110 men). The clinical factors and results of the 75-g oral glucose tolerance test were all recorded. Glycemic variability was assessed using continuous glucose monitoring. Compared with overweight or obese patients (BMI ≥ 24 kg/m2), underweight or normal-weight patients (BMI < 24 kg/m2) had higher levels of blood glucose fluctuation parameters, particularly in terms of mean amplitude of glycemic excursion (MAGE 6.64 ± 2.38 vs. 5.67 ± 2.05; P = 0.007) and postprandial glucose excursions (PPGEs) (PPGE at breakfast, 7.72 ± 2.79 vs. 6.79 ± 2.40, P = 0.028; PPGE at lunch, 5.53 ± 2.70 vs. 5.07 ± 2.40, P = 0.285; PPGE at dinner, 5.96 ± 2.24 vs. 4.87 ± 2.50, P = 0.008). BMI was negatively correlated with glycemic variability (r = -0.243, P = 0.002). On multiple linear regression analyses, BMI (β = -0.231, P = 0.013) and Insulin Secretion Sensitivity Index-2 (β = -0.204, P = 0.048) were two independent predictors of glycemic variability. In conclusion, lower BMI was associated with increased glycemic variability, characterized by elevated PPGEs, in newly diagnosed Chinese type 2 diabetic patients.Previous studies have indicated that the pathogenesis of diabetes differs between obese and lean patients. We investigated whether newly diagnosed Chinese diabetic patients with different body mass indices (BMIs) have different glycemic variability, and we assessed the relationship between BMI and glycemic variability. This was a cross-sectional study that included 169 newly diagnosed and drug-naïve type 2 diabetic patients (mean age, 51.33 ± 9.83 years; 110 men). The clinical factors and results of the 75-g oral glucose tolerance test were all recorded. Glycemic variability was assessed using continuous glucose monitoring. Compared with overweight or obese patients (BMI ≥ 24 kg/m2), underweight or normal-weight patients (BMI < 24 kg/m2) had higher levels of blood glucose fluctuation parameters, particularly in terms of mean amplitude of glycemic excursion (MAGE 6.64 ± 2.38 vs. 5.67 ± 2.05; P = 0.007) and postprandial glucose excursions (PPGEs) (PPGE at breakfast, 7.72 ± 2.79 vs. 6.79 ± 2.40, P = 0.028; PPGE at lunch, 5.53 ± 2.70 vs. 5.07 ± 2.40, P = 0.285; PPGE at dinner, 5.96 ± 2.24 vs. 4.87 ± 2.50, P = 0.008). BMI was negatively correlated with glycemic variability (r = −0.243, P = 0.002). On multiple linear regression analyses, BMI (β = −0.231, P = 0.013) and Insulin Secretion Sensitivity Index-2 (β = −0.204, P = 0.048) were two independent predictors of glycemic variability. In conclusion, lower BMI was associated with increased glycemic variability, characterized by elevated PPGEs, in newly diagnosed Chinese type 2 diabetic patients.

An Analysis of the Relationship Between Ankle–Brachial Index and Estimated Glomerular Filtration Rate in Type 2 Diabetes

We investigated the relationship between peripheral arterial disease (PAD) and renal function in patients with type 2 diabetes mellitus (T2DM). We enrolled 2057 hospitalized patients with T2DM and measured kidney function and ankle–brachial index (ABI). The estimated glomerular filtration rate (eGFR) was derived using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and ABI was grouped as low (<0.9), low-normal (0.9-1.09), normal (1.1-1.3), and high (>1.3). Logistic regression was used to evaluate the associations of eGFR with ABI. Generally speaking, the ABI was negatively correlated with systolic blood pressure, fasting C-peptide, total cholesterol, and low-density lipoprotein cholesterol while positively correlated with body mass index (P < .05 to <.01). Only a low ABI was positively correlated with eGFR (P < .01). In addition to the association of the ABI with cardiovascular events, stroke, and PAD, ABI may also predict the change in renal function in patients with T2DM.

Metformin add-on continuous subcutaneous insulin infusion on precise insulin doses in patients with type 2 diabetes

To investigate whether metformin add-on to the continuous subcutaneous insulin infusion (Met + CSII) therapy leads to a significant reduction in insulin doses required by type 2 diabetes (T2D) patients to maintain glycemic control, and an improvement in glycemic variation (GV) compared to CSII only therapy. We analyzed data from our two randomized, controlled open-label trials. Newly diagnoses T2D patients were randomized assigned to receive either CSII therapy or Met + CSII therapy for 4 weeks. Subjects were subjected to a 4-day continuous glucose monitoring (CGM) at the endpoint. Insulin doses and GV profiles were analyzed. The primary endpoint was differences in insulin doses and GV between the two groups. A total of 188 subjects were admitted as inpatients. Subjects in metformin add-on therapy required significantly lower total, basal and bolus insulin doses than those of control group. CGM data showed that patients in Met + CSII group exhibited significant reduction in the 24-hr mean amplitude of glycemic excursions (MAGE), the standard deviation, and the coefficient of variation compared to those of control group. Our data suggest that metformin add-on to CSII therapy leads to a significant reduction in insulin doses required by T2D patients to control glycemic variations.

Comparison of Efficacy and Safety of Lispro and Aspart Evaluated by Continuous Glucose Monitoring System in Patients with Newly Diagnosed Type 2 Diabetes

Objective To compare the effect of the rapid-acting insulin analogues (RAIAs) aspart (NovoRapid) and lispro (Prandilin) on glycemic variations by continuous glucose monitoring system (CGMS) in patients within newly diagnosed type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) and metformin intensive therapy. Methods This is a single-blind randomized controlled trial. A total of 110 patients with newly diagnosed T2DM and with hemoglobin A1c (HbA1c%) above 9% was hospitalized and randomly divided into two groups: group Asp (NovoRapid group) and group Lis (Prandilin group). They all received CSII and metformin therapy. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. C-peptide and insulin and fructosamine were determined. CGMS was continuously applied for 4 days after reaching the glycemic target. Results There were no significant differences in daily dosages of insulin, fasting plasma C-P and 2 h postprandial C-P and insulin, and fructosamine at the baseline and endpoint between the groups Asp and Lis. No significant differences were seen in the 24 h mean amplitude of glycemic excursions (MAGE), 24 h mean blood glucose (MBG), the standard deviation of the MBG (SDBG), fasting blood glucose, number of glycemic excursion (NGE), and the incidence of hypoglycemia between the two groups. Similarly, no significant differences were found in areas under the curve (AUC) of glucose above 10.0 mmol/L or the decremental area over the curve (AOC) of glucose below 3.9 mmol/L between the two groups. Conclusions Lispro and aspart had the similar ability to control the glycemic variations in patients with newly diagnosed T2DM. This study was registered with ClinicalTrials.gov, number ChiCTR-IPR-17010338.