Jin-dan Wu

Effect of Exenatide on Inflammatory and Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus

AIM This study was designed to determine the effect of exenatide on inflammatory and oxidative stress markers in type 2 diabetes mellitus (T2DM) patients who were suboptimally controlled with metformin and/or sulfonylurea. SUBJECTS AND METHODS Twenty-three patients with T2DM with inadequate glucose control were randomly divided into two groups: exenatide group (E group) (12 patients, 5 μg b.d. × 4 weeks followed by 10 μg b.d. × 12 weeks) and placebo group (P group) (11 patients). Glycosylated hemoglobin (HbA1c), the seven-point glucose profile, daily mean glucose, and glycemic excursion were determined. The effects of exenatide on 8-iso-prostaglandin F2α (PGF2α), monocyte chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hs-CRP) were investigated. RESULTS Exenatide treatment reduced body weight and body mass index (BMI) and improved HbA1c, the seven-point glucose profile, and daily mean glucose compared with placebo (P < 0.05). Limited glycemic excursion was found in the E group compared with the P group (P < 0.05), including a smaller SD and postprandial glucose excursion. In addition, the oxidative stress maker PGF2α was significantly reduced by exenatide treatment (P < 0.05). The inflammatory markers hs-CRP and MCP-1 were also significantly reduced in the E group compared with the P group (P < 0.05). PGF2α was significantly correlated with glycemic excursion (P < 0.05), whereas MCP-1 was significantly correlated with body weight, BMI, glycemic excursion, and HbA1c (P < 0.05 for all). CONCLUSIONS Exenatide treatment reduced patient body weight and BMI, improved HbA1c and the seven-point glucose profile, reduced daily mean glucose, limited glycemic excursion, and reduced oxidative stress and inflammatory markers in patients of T2DM having inadequate glucose control.

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.

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.

PGE1 improves diabetic peripheral neuropathy in patients with type 2 diabetes

BACKGROUND Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes. We aim to investigate the efficacy of Prostaglandin E1 (PGE1) treatment in addition to intensive insulin therapy on DPN in patients with type 2 diabetes. METHODS Seventy-seven patients with DPN received daily intravenous injection of Prostaglandin E1 (PGE1) in lipid microspheres (Lipo-PGE1) for 10days as an additional therapy to standard glucose control therapy (PGE1 group). Another 42 patients with DPN receiving only standard glucose control therapy (intensive insulin therapy) acted as a control group. Michigan neuropathy screening instrument (MNSI) score, neurophysiology examination, transcutaneous oxygen sensory threshold, and ankle-brachial index (ABI) were measured to evaluate the efficacy of PGE1 treatment as compared with control group. RESULTS Standard glucose control therapy decreased plasma glucose to a similar level in both PGE1 and control groups. Compare to control group, PGE1 group displayed improvement in several nerve electrophysiological indexes. MNSI score was significantly improved in patients who received PGE1 treatment compared with the control group (p<0.001) after 10days of PGE1 treatment. Similarly, nerve conduction velocity and foot sensory thresholds (p<0.05 for all) also significantly improved compared with the control group after 10days of PGE1 treatment. However, only intensive insulin therapy did not improve any neural function. CONCLUSIONS Lipo-PGE1 can effectively improve neural function of patients with DPN.

Fulminant Type 1 Diabetes Mellitus: A Study of Nine Cases

OBJECTIVE The study aims to explore the prevalence and clinical features of fulminant type 1 diabetes mellitus (F1DM). SUBJECTS AND METHODS We analyzed 11,202 patients who were diagnosed having diabetes and admitted to the Department of Endocrinology, Nanjin First Hospital, Nanjin, China, from September 2005 to April 2011. Among 198 patients classified having type 1 diabetes mellitus (T1DM), nine patients were diagnosed having F1DM. Clinical features of F1DM were analyzed and compared with typical T1DM. RESULTS The prevalence of F1DM was 4.5% (nine of 198 T1DM patients) in this study. F1DM patients had significantly high levels of random blood glucose (40±9 mmol/L). However, glycated hemoglobin (7.1±1.0%) and C-reactive peptide (0.21±0.15 μg/L) at 2 h postprandial were significantly lower in F1DM patients compared with typical T1DM patients. Six of them had flu-like symptoms. Five of them showed gastrointestinal symptoms. Three patients experienced disturbance of consciousness. However, none of these symptoms was found in patients with typical T1DM. A continuous intravenous insulin infusion therapy using a portable pump was given during the acute phase to control hyperglycemia and ketoacidosis. All F1DM patients survived after treatment. CONCLUSION In this single hospital-based study, nine Chinese patients met the criteria for diagnosis of F1DM. Although F1DM may be fatal, prompt treatment is required and useful to rescue these patients.