Daily Glucose Fluctuations Research Articles

Relationship between indices of daily glycemic variability and long-term glucose fluctuations

Relationship between indices of daily glycemic variability and long-term glucose fluctuations

Effects of daily glucose fluctuations on the healing response to everolimus-eluting stent implantation as assessed using continuous glucose monitoring and optical coherence tomography.

BackgroundSeveral studies have revealed that glucose fluctuations provoke oxidative stress that leads to endothelial cell dysfunction, progression of coronary atherosclerosis, and plaque vulnerability. However, little is known regarding their effect on neointimal growth after stenting in patients with coronary artery disease (CAD). We aimed to investigate the effects of glucose fluctuations on neointimal growth after everolimus-eluting stent (EES) implantation.MethodsThis study examined 50 patients who underwent a 9-month follow-up using optical coherence tomography (OCT) after EES implantation. Glucose fluctuation was expressed as the mean amplitude of glycemic excursion (MAGE), and was determined via continuous glucose monitoring before stenting. At the OCT follow-up, we evaluated the percentage of uncovered struts and three-dimensional uniformity of neointimal distribution by calculating the mean neointimal thickness (NIT) within 360 equally-spaced radial sectors for every 1-mm cross-sectional OCT analysis, and assessed the incidence of major adverse cardiovascular events (MACE).ResultsWe evaluated 60 lesions in 50 patients. Linear mixed effect models were used to explore the influence of different variables on variability in NIT and the percentage of uncovered struts and to adjust for covariates. Univariate analysis showed that MAGE was most strongly correlated with the previously mentioned OCT measurements (coefficient β ± standard error = 0.267 ± 0.073 and 0.016 ± 0.003, t = 3.668 and 6.092, both P < 0.001, respectively). In multivariate analysis, MAGE had the strongest effect on variability in NIT (coefficient β ± standard error = 0.239 ± 0.093, P = 0.014) and the percentage of uncovered struts (coefficient β ± standard error = 0.019 ± 0.004, P < 0.001). Five lesions in four patients required target lesion revascularization (10.0 %) at a mean duration of 9 months after EES implantation. Compared to non-MACE cases, cases of MACE exhibited a significantly higher MAGE (99 vs. 68; P = 0.004), maximum NIT (580 vs. 330 µm; P = 0.002), and variability in NIT (100 vs. 65; P = 0.007), although there was no significant difference in these groups’ HbA1c levels.ConclusionsGlucose fluctuation may affect vessel healing after EES implantation in patients with CAD who are receiving lipid-lowering therapy. Therefore, glucose fluctuations may be an important target for secondary prevention after coronary stenting, which is independent of dyslipidemia control.

Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea

Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24 hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea.Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N = 73) with T2DM who had inadequate glycemic control (HbA1c 7.0%–10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50 mg twice daily (BID, n = 37) or saxagliptin 5 mg once daily (QD, n = 36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks.Results At baseline, the mean (±SD) age was 62.9 ± 6.55 years, disease duration was 7.0 ± 2.33 years, and HbA1c was 8.4 ± 0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81 ± 1.16 mmol/L to 4.06 ± 0.86 mmol/L (p<0.001) in the vildagliptin group and from 5.66 ± 1.14 mmol/L to 4.79 ± 1.25 mmol/L (p = 0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74 ± 0.48 mmol/L vs. 0.87 ± 0.40 mmol/L, p<0.001). The mean change in HbA1c, from baseline to the study endpoint, in the vildagliptin and saxagliptin groups, was 1.22 ± 0.40% and 1.07 ± 0.36%, respectively, with no significant difference between the groups (p = 0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug.Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM.Chinese clinical trial registration number ChiCTR-TRC-13003858.

TCT-342 Impact of Daily Glucose Fluctuation on Vessel Healing after 2nd Generation Drug-eluting Stent Implantation Assessed by Continuous Glucose Monitoring and Optical Coherence Tomography

Several investigations revealed that daily glucose fluctuation has adverse effects on endothelial cells. Moreover, we reported that it may have an independent contributing factor on coronary plaque vulnerability. Little is known, however, about its impact on neointimal growth after stenting in

Association between daily glucose fluctuation and coronary plaque properties in patients receiving adequate lipid-lowering therapy assessed by continuous glucose monitoring and optical coherence tomography.

BackgroundGlucose fluctuation has been recognized as a residual risk apart from dyslipidemia for the development of coronary artery disease (CAD). This study aimed to investigate the association between glucose fluctuation and coronary plaque morphology in CAD patients.MethodsThis prospective study enrolled 72 consecutive CAD patients receiving adequate lipid-lowering therapy. They were divided into 3 tertiles according to the mean amplitude of glycemic excursions (MAGE), which represents glucose fluctuation, measured by continuous glucose monitoring (tertile 1; <49.1, tertile 2; 49.1 ~ 85.3, tertile 3; >85.3). Morphological feature of plaques were evaluated by optical coherence tomography. Lipid index (LI) (mean lipid arc × length), fibrous cap thickness (FCT), and the prevalence of thin-cap fibroatheroma (TCFA) were assessed in both culprit and non-culprit lesions.ResultsIn total, 166 lesions were evaluated. LI was stepwisely increased according to the tertile of MAGE (1958 ± 974 [tertile 1] vs. 2653 ± 1400 [tertile 2] vs. 4362 ± 1858 [tertile 3], p <0.001), whereas FCT was the thinnest in the tertile 3 (157.3 ± 73.0 μm vs. 104.0 ± 64.1 μm vs. 83.1 ± 34.7 μm, p <0.001, respectively). The tertile 3 had the highest prevalence of TCFA. Multiple linear regression analysis showed that MAGE had the strongest effect on LI and FCT (standardized coefficient β = 0.527 and −0.392, respectively, both P <0.001). Multiple logistic analysis identified MAGE as the only independent predictor of the presence of TCFA (odds ratio 1.034; P <0.001).ConclusionsGlucose fluctuation and hypoglycemia may impact the formation of lipid-rich plaques and thinning of fibrous cap in CAD patients with lipid-lowering therapy.

Effect of daily glucose fluctuation on coronary plaque vulnerability in patients pre-treated with lipid-lowering therapy: a prospective observational study.

This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy. There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD. This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit lesions were assessed by virtual histology intravascular ultrasound, and the volume percentage of necrotic core within the plaque (%NC) and the presence of thin-cap fibroatheroma were evaluated. In total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p <0.001). A linear mixed effect model showed that MAGE had the strongest effect on %NC (coefficient β = 0.080 ± 0.020 [standard error], p < 0.001). The generalized linear mixed effect model revealed that MAGE was the only independent predictor of the presence of thin-cap fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p = 0.007). Daily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients.

Percutaneous coronary interventions in the diabetic patient: where do we stand?

Clinical observations made during the past 20 years have suggested that patients with diabetes mellitus (DM) have suboptimal outcomes after percutaneous coronary interventions (PCIs).1–4 During the same time period, mechanistic studies have provided insights into the cardiovascular risk of DM. In this report, we attempt to synthesize observations made in the experimental laboratory with those made in the clinical setting to identify how diabetic traits may compromise the success of PCI (Figure 1). Figure 1. Diabetic traits potentially compromising the success of percutaneous coronary intervention. The hallmarks of DM are hyperglycemia, insulin resistance or an absolute lack of endogenous insulin, and hyperinsulinemia. These metabolic derangements may lead to premature atherosclerosis, cardiomyocyte dysfunction, and renal failure through several mechanisms. ### Diabetic Arteriopathy In an early stage of atherogenesis, the presence of cholesterol crystals may induce the formation of small hydroxyapatite mineral clefts, which are also called microcalcifications, in the intima or media.5 In DM, medial calcification develops independently of hypercholesterolemia and may cause sheet-like calcific deposits that reduce vascular compliance.6 In the presence of hyperglycemia, medial calcification may be mediated by a glycosylation process, in which N-acetylglucosamine (O-GlcNAc) binds to serine and threonine residues of vascular proteins.7 In a drug-induced mouse model of type 1 DM, Heath et al6 found a strong increase in vascular O-GlcNAcylation after the onset of increased blood glucose levels, along with a significant increase in aortic calcium content and vascular stiffness. The connection between O-GlcNAcylation and the development of a mineralized matrix was confirmed in an experimental model of vascular smooth muscle cells cultured in osteogenic differentiation media along with an inhibitor of N-acetylglucosaminidase.6 The formation of vulnerable atherosclerotic lesions may be related to hyperglycemia8 or insulin resistance.9 Kuroda et al8 observed that daily glucose fluctuations, measured as the …

Effects of sitagliptin or mitiglinide as an add-on to acarbose on daily blood glucose fluctuations measured by 72 h subcutaneous continuous glucose monitoring in Japanese patients with type 2 diabetes: a prospective randomized study

Objective: Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life.Methods: Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 – 7 days in week 3 of each treatment period.Results: The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period.Conclusion: Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.

Effect of repaglinide versus glimepiride on daily blood glucose variability and changes in blood inflammatory and oxidative stress markers.

BackgroundHemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages.MethodsContinuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide.ResultsNine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment.ConclusionThese results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress.

Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076-2082

In the article listed above, the source of funding for the study was not specified. The study was funded by an Institutional Grant of the Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples. Also, the MAGE data were manually calculated …

Extended distal pancreatectomy for advanced pancreatic neck cancer.

Backgrounds/AimsWe investigated the clinical application of extended distal pancreatectomy in patients with pancreatic neck cancer accompanied by distal pancreatic atrophy. In this study, we have emphasized on the technical aspects of using the linear stapling device for a bulky target organ.MethodsFrom March 2010 to September 2013, 46 patients with pancreatic adenocarcinoma, who underwent pancreatic resection with radical intent at our institute, were reviewed retrospectively. Among them, three patients (6.5%) underwent extended distal pancreatectomy. A linear stapling device and vise-grip locking pliers were used for en bloc resection of the distal pancreas, first duodenal portion, and distal common bile duct. The results were compared with those after standard pancreatectomy.ResultsAll three patients presented with jaundice, and the ratio of pancreatic duct to parenchymal thickness of the pancreatic body was greater than 0.5. Grade A pancreatic fistula developed in all of the cases, but none of these fistulae were lethal. Pathological staging was T3N1M0 in all of the patients. The postoperative daily serum glucose fluctuations and insulin requirements were comparable to those in patients who received pancreaticoduodenectomy or distal pancreatectomy. At the last follow-up, two patients were alive with liver metastasis at 4 and 10 months postoperatively, respectively, and one patient died of liver metastasis at 5 months postoperatively.ConclusionsWhile the prognosis of advanced pancreatic neck adenocarcinoma is still dismal, extended distal pancreatectomy is a valid treatment option, especially when there is atrophy of the distal pancreas. Also, the procedure is technically feasible, and further refinement is necessary to improve patient survival.

Short-term effects of low-dose estrogen/drospirenone vs low-dose estrogen/dydrogesterone on glycemic fluctuations in postmenopausal women with metabolic syndrome

This study aims to compare the effects of low-dose emidrate estradiol/drospirenone (E2/DRSP) vs low-dose emidrate estradiol/dydrogesterone (E2/DG) combination on the mean amplitude of glycemic excursions (MAGE) value in postmenopausal women affected by metabolic syndrome (MS). One hundred sixty postmenopausal women were recruited to receive a treatment with oral doses of E2/1 mg plus drospirenone/2 mg (E2/DRSP group) or oral dose of E2/1 mg plus dydrogesterone/5 mg (E2/DG group) for 6 months. At enrollment and after 6 months, anthropometric, metabolic, and inflammatory parameters have been assessed. MAGE, evaluated during 48-h continuous subcutaneous glucose monitoring (CSGM), allowed us to assess daily glucose fluctuations at baseline and after 6 months. After hormone therapy, both groups showed a significant decline in fasting plasma glucose levels (p < 0.05), while only E2/DRSP group showed a statistically significant decline in waist circumferences, post-prandial glycemia, LDL, plasma triglycerides, MAGE, HOMA index, and plasma IL-6 (p < 0.05) levels. In the whole population (n = 160), after 6 months of indicated therapy, changes in fasting plasma glucose and PAI-1 levels correlated with the changes in MAGE values, while only in E2/DRSP group that MAGE reduction was positively associated with a stronger decrease in waist circumferences, triglycerides, and TNF-α plasma levels. The independent effect of hormone therapy (HT) on reduction in MAGE value has been tested in three different multiple linear regression models. HT resulted to be associated with MAGE, independent of other confounding variables. Although both groups had a decline in fasting plasma glucose, only drospirenone treatment revealed positive effects on glycemic excursions and insulin sensitivity, induced favorable changes in lipid profile, and showed an improvement of inflammatory indices in postmenopausal women with MS.

Comment on: Rizzo et al. Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076–2082

In their interesting study on the concomitant reduction in inflammatory and oxidative stress and mean amplitude of glycemic excursions (MAGE) following treatment with dipeptidyl peptidase-IV (DPP-4) inhibitors, sitagliptin and vildagliptin, in patients with type 2 diabetes, Rizzo et al. (1) propose that the reduction in MAGE leads to the reduction in indices of oxidative and inflammatory stress. However, the recent demonstration that sitagliptin exerts a rapid and potent …

Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors

ObjectiveBlood glucose fluctuations have been found to be relevant to the progression of atherosclerosis in patients with type 2 diabetes and to be more detrimental for the development of atherosclerosis than the sustained hyperglycemia. We aim at evaluating the effect of blunted daily acute glucose fluctuations by DPP-IV inhibitors on intima-media thickness (IMT), a surrogate marker for early atherosclerosis. MethodsData from a 12-week prospective, randomized, open-label parallel group trial with a blinded-endopoint study on 90 patients with DMT2, assessing the role of Dipeptidyl Peptidase-4 inhibition in lowering oxidative stress and inflammation by reducing daily acute glucose fluctuations (MAGE), were included in the present analysis. ResultsAdministration of both sitagliptin and vildagliptin treatment resulted in a significant decline in IMT. Indeed, vs baseline data Vildagliptin vs Sitagliptin resulted in a greater IMT reduction.After 3 months therapy changes in IMT significantly correlated with changes in MAGE but not with change in HbA1c in the whole population. Only change in MAGE and LDL plasma levels resulted to be independent predictors of the reduced carotid intima-media thickness after adjusting for conventional cardiovascular risk factors in patients with type 2 diabetes. Significant correlations between change in MAGE, change in IMT and change in fasting and interprandial inflammation score and nitrotyrosine plasma levels were found. ConclusionReduction of glucose excursion due to DPP-IV inhibitors administration, may prevent atherosclerosis progression in patients with type 2 diabetes probably through the reduction of daily inflammation and oxidative stress.

Efficacy and safety of sitagliptin as add-on therapy on glycemic control and blood glucose fluctuation in Japanese type 2 diabetes subjects ongoing with multiple daily insulin injections therapy

To assess the efficacy and safety of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in subjects with type 2 diabetes inadequately controlled with multiple daily insulin injections therapy (MDI). HbA1c, 1,5-anhydroglucitol (1,5-AG), body mass index (BMI), insulin doses, six-point self-measured plasma glucose (SMPG) profiles were assessed before, after 12 weeks, and after 24 weeks of MDI with 50 mg/day of sitagliptin in 40 subjects with type 2 diabetes. Safety endpoints included hypoglycemia and any adverse events. HbA1c significantly decreased during the first 12 weeks ( -0.64±0.60%), and was sustained over 24 weeks ( -0.69±0.85%). 1,5-AG increased significantly from 7.5±4.5 μg/mL at baseline to 9.6±5.5 μg/mL after 24 weeks. The bolus insulin dose at 12 weeks was decreased, and the mean plasma glucose, the SD of daily glucose, M-value, and the mean amplitude of glycemic excursions (MAGE) also decreased significantly as compared with baseline values. BMI and frequency of hypoglycemia were not changed significantly. Univariate linear regression analyses revealed that % change in HbA1c was significantly associated with BMI, and % changes in the indexes of glycemic instability (SD of daily glucose and MAGE) were significantly associated with age. In conclusion, adding sitagliptin to MDI significantly improved glycemic control and decreased the daily glucose fluctuation in subjects with type 2 diabetes inadequately controlled with MDI, without weight gain or an increase in the incidence of hypoglycemia. This trial was registered with UMIN (no. UMIN000010157).

Glucose Fluctuations during Gestation: An Additional Tool for Monitoring Pregnancy Complicated by Diabetes.

Continuous glucose monitoring (CGM) gives a unique insight into magnitude and duration of daily glucose fluctuations. Limited data are available on glucose variability (GV) in pregnancy. We aimed to assess GV in healthy pregnant women and cases of type 1 diabetes mellitus or gestational diabetes (GDM) and its possible association with HbA1c. CGM was performed in 50 pregnant women (20 type 1, 20 GDM, and 10 healthy controls) in all three trimesters of pregnancy. We calculated mean amplitude of glycemic excursions (MAGE), standard deviation (SD), interquartile range (IQR), and continuous overlapping net glycemic action (CONGA), as parameters of GV. The high blood glycemic index (HBGI) and low blood glycemic index (LBGI) were also measured as indicators of hyperhypoglycemic risk. Women with type 1 diabetes showed higher GV, with a 2-fold higher risk of hyperglycemic spikes during the day, than healthy pregnant women or GDM ones. GDM women had only slightly higher GV parameters than healthy controls. HbA1c did not correlate with GV indicators in type 1 diabetes or GDM pregnancies. We provided new evidence of the importance of certain GV indicators in pregnant women with GDM or type 1 diabetes and recommended the use of CGM specifically in these populations.

Response to Comment on: Rizzo et al. Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076–2082

DeVries (1) was surprised that vildagliptin and sitagliptin groups reported different mean amplitude of glycemic excursions (MAGE) reduction because they have similar fasting and postprandial glucose levels and suggested reporting other measures of glucose variability to better understand these results. Indeed, a previous study evaluating the role of glycemic variability in type 2 diabetic patients has demonstrated that patients with similar mean glucose and postprandial glucose have a markedly different daily glucose profile with differences both in number and duration of excursions (2). The difference in MAGE reduction found in the two study groups …

Comment on: Rizzo et al. Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076–2082

Rizzo et al. (1) report some remarkable differences in mean absolute glucose excursions (MAGE), markers of oxidative stress, and markers of inflammation in a randomized, open-label trial of sitagliptin 100 mg once daily versus vildagliptin 50 mg twice daily. MAGE is a measure of large glycemic swings, taking into account only …

Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes

OBJECTIVEEvaluate the effects of two dipeptidyl peptidase-IV (DPP-4) inhibitors, sitagliptin and vildagliptin, known to have different efficacy on mean amplitude of glycemic excursions (MAGE), on oxidative stress, and on systemic inflammatory markers in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSA prospective, randomized, open-label PROBE design (parallel group with a blinded end point) study was performed in 90 patients with type 2 diabetes inadequately controlled by metformin. The study assigned 45 patients to receive sitagliptin (100 mg once daily; sitagliptin group) and 45 patients to receive vildagliptin (50 mg twice daily; vildagliptin group) for 12 weeks. MAGE, evaluated during 48 h of continuous subcutaneous glucose monitoring, allowed an assessment of daily glucose fluctuations at baseline and after 12 weeks in all patients. Assessment of oxidative stress (nitrotyrosine) and systemic levels of inflammatory markers interleukin (IL)-6 and IL-18 was performed at baseline and after 12 weeks in all patients.RESULTSHbA1c, fasting and postprandial glucose, MAGE, and inflammatory and oxidative stress markers were similar between the groups at baseline. After 12 weeks, MAGE (P < 0.01) was lower in the vildagliptin group than in the sitagliptin group. After treatment, HbA1c and postprandial glucose evidenced similar changes between the groups (P = NS). Vildagliptin treatment was associated with a stronger decrease in nitrotyrosine (P < 0.01), IL-6 (P < 0.05), and IL-18 (P < 0.05) than sitagliptin treatment. Nitrotyrosine and IL-6 changes significantly correlated with changes in MAGE but not in fasting glucose and HbA1c.CONCLUSIONSMAGE reduction is associated with reduction of oxidative stress and markers of systemic inflammation in type 2 diabetic patients. These effects were greater in the vildagliptin group than in the sitagliptin group.

Continuous glucose monitoring in the patients with diabetic nephropathy

The aim of this study was to compare the difference of blood glucose (BG) fluctuation in the patients of type-2 diabetes mellitus (DM-2) with and without clinical diagnosed diabetic nephropathy (DN) by the continuous glucose monitoring system (CGMS). Thirty DM-2 patients with clinical diagnosed DN and fifteen DM-2 patients without complication underwent continuous glucose monitoring for 3 days (72 h) by CGMS. The difference of daily glucose fluctuation in both groups was compared by the parameter of CGMS. The 24-h mean blood glucose (MBG), minimal BG (MIN-BG), area under curve of BG over 7.8 (AUC7.8), percentage of time of BG over 7.8 (PT7.8), area under curve of BG over 11.1 (AUC11.1), percentage of time of BG over 11.1 (PT11.1), as well as mean of daily difference (MODD) were significantly increased in the group of DN, compared with those in the group of DM-2 without complication (all statistic probability P <0.05). No statistical significance of mean amplitude of glycaemic excursion (MAGE) was found. In the group of DN, MBG, standard deviation of blood glucose (SDBG), large amplitude of glycaemic excursion (LAGE), AUC7.8, PT7.8, AUC11.1, PT11.1, MAGE and MODD were (10.7±1.9)mmol/L, (2.5±1.3)mmol/L, (9.2±3.9)mmol/L, 3.2±1.7, (81±18)%, 1.2±1.0, (42±24)%, (5.8±2.5)mmol/L and (2.6±1.5)mmol/L, respectively. The study showed that the BG level of the patients with DN fluctuated throughout the day. MBG of the patients with DN was higher than that of the patients of DM-2 without complications, with the characteristics of long-lasting high BG period, dramatic instability during the day and especially high postprandial blood glucose. CGMS is a useful tool for physicians to know the details of the change of BG in the patients with DN.