Mean Postprandial Glucose Excursion Research Articles

Reduction in Postprandial Peak Glucose With Increased Technosphere Insulin Dosage.

Technosphere Insulin (TI) is an ultra-rapid-acting inhaled insulin. This study assessed the mean peak two-hour postprandial glucose concentration with the initial TI dose (dose 1) calculated per the current label (United State Prescribing Information) compared with a ~2× higher dose (dose 2). Secondary objectives were to evaluate hypoglycemia within the two-hour postprandial period, evaluate change in forced expiratory volume in one second (FEV1) before and after the two-hour postprandial period, and monitor for other adverse events. Twenty patients with diabetes, on basal-bolus insulin therapy, received an initial dose 1 of TI followed by the higher dose 2, one to three days later. Subjects received an identical meal for both visits, and TI doses were administered immediately prior to the meal. The higher dose 2 provided significant reductions in mean postprandial glucose excursion (PPGE) in the two-hour postprandial period starting from 45 minutes (P = .008) to 120 minutes (P < .0001). Mean peak glucose was reduced from 228.6 to 179.3 mg/dL (P < .001) at two hours. Two hypoglycemic events (one level 1, one level 2) were observed in a single subject during the two-hour postprandial period with dose 2. There were no significant changes in FEV1 after either dose of TI. The higher dose 2 reduced PPGE versus the current label recommended dose 1 within the two-hour postprandial timeframe without any new safety concerns. When confirmed with a larger study, this higher TI dosing recommendation may help patients and clinicians minimize immediate postprandial hyperglycemia when titrating TI for prandial glucose control.

Additional insulin dosing for fat and protein in children with type 1 diabetes using multiple daily injections

High-fat high-protein (HFHP) meals are associated with post-prandial hyperglycemia in type 1 diabetes (T1D), administration of additional insulin for such meals is recommended in order to optimize glucose levels. Optimal timing of additional insulin for HFHP meals in children and young people receiving multiple daily injections (MDI) remains unclear. To investigate the glycemic impact of additional insulin doses given before or after eating a HFHP meal in children with T1D using MDI. A randomized, controlled three period crossover trial of 27 participants aged 13 years (6.1-17.7) at two Pediatric Diabetes centers was conducted. Additional rapid-acting insulin for the fat-protein content of a standardized HFHP meal was given at three time points calculated using an algorithm extrapolated from current evidence base and clinical recommendations. Post-prandial glucose (PPG) parameters were calculated for 420minutes using continuous glucose monitoring. The primary outcome was mean PPG excursion. Secondary outcomes included peak glucose, time to peak and hypoglycemia incidence. There was no difference in post-prandial glucose parameters when additional HFHP insulin was administered at mean glucose excursion (mmol/L) (SE): 1.9(0.7), 1.2(0.7), 2.5(0.7); p= 0.5); mean peak glucose (mmol/L)(SE): 10.9(0.9), 11.5(0.8), 11.5(0.9); p= 0.9; time to peak glucose (mins)(SE): 82.3(35.4), 113.6(30.9), 95.1(32.1); p= 0.8. Mild hypoglycemia was common (55%) in all groups (p= 0.97). We found no benefit in giving additional insulin as a split dose for HFHP meals in children using MDI, mild hypoglycemia was common. Future studies would benefit from refinement of the insulin dose algorithm.

2183-PUB: Standard Deviation Calculated from the 7-Point SMBG Glucose Profiles Is a Good Index of Glycemic Variability Reflecting MAGE Obtained from CGMS

Objective: Mean amplitude of glucose excursion (MAGE) obtained from the CGMS is considered a gold standard of glycemic variability (GV). However, the implications of CGMS in routine clinical practice are limited due to its high cost and complexity. This study thus designed to explore whether the GV indices calculated from the more common measurement SMBG can be used to reflect MAGE in T2D patients. Methods: T2D patients simultaneously underwent a 48-h to 72-h CGM and fingertip blood glucose self-monitoring were included. The GV indices calculated from the 7-point SMBG data (pre- and post- breakfast, lunch and dinner and prior to bedtime) were the means of the following indices during CGM period: the standard deviation (SD) of the 7-point glucose profiles, the largest amplitude of glycemic excursions (LAGE, the difference between the daily maximum and minimum glycemic values) and the mean postprandial glucose excursion (MPPGE, the mean value of the differences between each postprandial and preprandial blood glucose). Results: Seventy-eight T2D patients (43.6% male, median age: 62 years, median BMI: 23.83 kg/m2) were included. The mean MAGE, SD, LAGE and MPPGE were 4.11, 2.03, 5.66, 2.57mmol/L, respectively. SD, LAGE and MPPGE were significantly correlative with MAGE (r= 0.625, 0.488 and 0.599, respectively; all P&amp;lt;0.05). In the linear regression analysis, significant relationships were shown between MAGE and SD, LAGE and MPPGE (R2=0.391, 0.359, 0.238, respectively; all P&amp;lt;0.001). The area under the ROC curve for SD (0.809, 95% CI: 0.712-0.906, P&amp;lt;0.05) was superior to that for LAGE (0.793, 95% CI: 0.692-0.894, P&amp;lt;0.05) and MPPGE (0.704, 95% CI: 0.588-0.820, P&amp;lt;0.05) in reflecting MAGE. Conclusions: The GV indices calculated from the SMBG data including SD, LAGE and MPPGE are positively correlated with MAGE obtained from CGM. Among these indices, SD of the 7-point SMBG glucose profiles seems to be a better GV index to reflect MAGE. Disclosure Z. Liu: None. B. Lin: None. W. Xu: None. L. Gong: None. X. Yang: None. B. Yao: None. Funding National Key Research and Development Program of China (2016YFC1304801)

Efficacy and Safety of Tofogliflozin on 24-h Glucose Profile Based on Continuous Glucose Monitoring: Crossover Study of Sodium-Glucose Cotransporter 2 Inhibitor.

Background: To compare the impact of two sodium-glucose cotransporter 2 (SGLT2) inhibitors, tofogliflozin and ipragliflozin, on hypoglycemia in patients with type 2 diabetes mellitus (T2DM), treated with sulfonylureas. Methods: Thirty patients with T2DM were allocated to treatment with either 20 mg/day tofogliflozin or 50 mg/day ipragliflozin and underwent continuous glucose monitoring (CGM) for 5 days at three times in a crossover manner. Results: The percent time spent at glucose <70 mg/dL per 24 h was 0.48, 2.77, and 0.06%, before treatment with SGLT2 inhibitors and treatment with ipragliflozin and tofogliflozin, respectively (P = 0.1135, difference between SGLT2 inhibitors). The addition of either ipragliflozin or tofogliflozin to sulfonylureas markedly and significantly improved other CGM-derived parameters, including average plasma glucose, standard deviation of glucose, mean postprandial glucose excursion, percent time with glucose >140, >180 mg/dL, and >200 mg/dL, area over the curve <70, area under the curve >140, >180, and >200, and maximum and minimum plasma glucose. However, there were no significant differences in these parameters between the two SGLT2 inhibitors. Conclusions: Based on the CGM, the addition of tofogliflozin to sulfonylureas tended to decrease the percent time spent in hypoglycemia in T2DM patients. The addition of SGLT2 inhibitors to sulfonylureas improved the average glucose level and reduced glucose fluctuations without increasing the time in hypoglycemia.

2358-PUB: Efficacy and Safety of Tofogliflozin on 24-hr Glucose Profile Based on Continuous Glucose Monitoring—Crossover Study of Sodium-Glucose Cotransporter 2 Inhibitor

Background: Tofogliflozin (TOFO) has the highest selectivity to sodium-glucose co-transporter 2 (SGLT2) relative to SGLT1 (2900 times) and does not promote urinary glucose excretion at hypoglycemia compared with phlorhizin and does not enhance further lowering of glucose. To compare the impact of TOFO and ipragliflozin (IPR) on hypoglycemia in patients with T2DM, treated with sulfonylureas. Methods: 30 patients were allocated to either 20 mg TOFO or 50 mg IPR and wore a continuous glucose monitoring (CGM, ipro2®) for 5 days at 3 times in a cross-over manner. The primary outcome measure was proportion of time over 24 hours with glucose less than 70 mg/dl detected by CGM and this was compared between two SGLT2 inhibitors. Results: The percent time spent at glucose less than 70 mg/dl was 0.48, 2.77 and 0.06%, before treatment with SGLT2 inhibitors and treatment with IPR and TOFO (p=0.1135, between SGLT2 inhibitors). The addition of either IPR or TOFO to sulfonylureas markedly and significantly improved other CGM-derived parameters including average glucose, standard deviation of glucose, mean postprandial glucose excursion, percent time with glucose &amp;gt;140, &amp;gt;180 and &amp;gt;200 mg/dl, area over the curve &amp;lt;70, area under the curve &amp;gt;140, &amp;gt;180 and &amp;gt;200, maximum glucose. However, there were no significant differences in these parameters between the SGLT2 inhibitors. We also conducted a sub-analysis in 16 patients who received DPP-4 inhibitors. The results showed the percent time at glucose level &amp;lt;70 mg/dl (p=0.1118, between SGLT2 inhibitors) and the area over the curve &amp;lt;70 (p=0.0631, between SGLT2 inhibitors), tended to be lower in patients treated with TOFO. Conclusion: Based on the CGM the addition of TOFO to sulfonylureas tended to decrease the percent time spent in hypoglycemia in T2DM. The addition of SGLT2 inhibitors to sulfonylureas improved the average glucose level and reduced glucose fluctuations without increasing hypoglycemia. Disclosure A. Kurozumi: None. Y. Okada: None. Y. Goshima: None. T. Otsuka: None. M. Narisawa: None. K. Torimoto: None. Y. Tanaka: None.

Risk Factors of Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Study Based on Continuous Glucose Monitoring

The objective of this study was to determine the risk factors of hypoglycemia by evaluating the glycemic profile using continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM). The participants were 294 patients with T2DM who received inpatient diabetes education. The mean blood glucose (MBG), coefficient of variation (CV), mean postprandial glucose excursion, low blood glucose index (LBGI), and percentage of time with blood glucose (BG) at <70 mg/dL were measured on admission using CGM. We predicted the risk of hypoglycemia utilizing transform to Gaussian model. The primary end point was the relationship between CGM parameters and hypoglycemia. Multivariate logistic regression analysis showed that disease duration, MBG, CV, LBGI, and Predicted% of BG correlated significantly with hypoglycemia. Receiver operating characteristic curve analysis showed that the optimal cutoff points for MBG and CV in predicting hypoglycemia were 152 mg/dL and 22%, respectively. The proportion of patients with hypoglycemia was 0% for the group with no hypoglycemia risk factors, 4.2% for the group with one risk factor, and 36.6% for the group with two risk factors, showing a linear increase across the groups (P < 0.001). LBGI was the best predictor of hypoglycemia; and Predicted% BG <70 mg/dL was very useful as an index to predict hypoglycemia. Patients with low MBG levels and large fluctuations in BG were more likely to develop hypoglycemia, suggesting that assessment of these two variables is useful for the prediction of hypoglycemia. To achieve good glycemic control free of hypoglycemia, approaches are needed that do not only lower BG level but also minimize fluctuations in blood and interstitial fluid glucose level.

Determinants of hemoglobin A1c level in patients with type 2 diabetes after in-hospital diabetes education: A study based on continuous glucose monitoring.

Aims/IntroductionWe investigated the relationship between blood glucose profile at hospital discharge, evaluated by continuous glucose monitoring (CGM), and hemoglobin A1c (HbA1c) level at 12 weeks after discharge in patients with type 2 diabetes who received inpatient diabetes education.Materials and MethodsThis was a retrospective study. The participants were 54 patients with type 2 diabetes who did not change their medication after discharge. The mean blood glucose (MBG), standard deviation, coefficient of variation, mean postprandial glucose excursion, maximum blood glucose, minimum blood glucose, percentage of time with blood glucose at ≥180 mg/dL (time at ≥180), percentage of time with blood glucose at ≥140 mg/dL, and percentage of time with blood glucose at <70 mg/dL were measured at admission and discharge using CGM. The primary end‐point was the relationship between CGM parameters and HbA1c level at 12 weeks after discharge.ResultsThe HbA1c level at 12 weeks after discharge correlated with MBG level (r = 0.30, P = 0.029). Multivariate analysis showed that MBG level and disease duration were predictors of 12‐week HbA1c level. Multivariate logistic regression analysis was carried out considering goal achievement as a HbA1c level <7.0% 12 weeks after discharge. Disease duration and time at ≥180 were associated with goal achievement.ConclusionsThe present results suggested that blood glucose profile at discharge using CGM seems useful to predict HbA1c level after discharge in patients with type 2 diabetes who received inpatient diabetes education. Early treatment to improve MBG level, as well as postprandial hyperglycemia, is important to achieve strict glycemic control.

Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus

BackgroundFluctuations in blood glucose level cause endothelial dysfunction and play a critical role in onset and/or progression of atherosclerosis. We hypothesized that fluctuation in blood glucose levels correlate with vascular endothelial dysfunction and that this relationship can be assessed using common bedside medical devices.MethodsFluctuations in blood glucose levels were measured over 24 hours by continuous glucose monitoring (CGM) on admission day 2 in 57 patients with type 2 diabetes mellitus. The reactive hyperemia index (RHI), an index of vascular endothelial function, was measured using peripheral arterial tonometry (EndoPAT) on admission day 3.ResultsThe natural logarithmic-scaled RHI (L_RHI) correlated with SD (r=−0.504; P<0.001), the mean amplitude of glycemic excursions (MAGE) (r=−0.571; P<0.001), mean postprandial glucose excursion (MPPGE) (r=−0.411; P=0.001) and percentage of time ≥200 mg/dl (r=−0.292; P=0.028). In 12 patients with hypoglycemia, L_RHI also correlated with the percentage of time at hypoglycemia (r=−0.589; P=0.044). L_RHI did not correlate with HbA1c or fasting plasma glucose levels. Furthermore, L_RHI did not correlate with LDL cholesterol, HDL cholesterol, and triglyceride levels or with systolic and diastolic blood pressures. Finally, multivariate analysis identified MAGE as the only significant determinant of L_RHI.ConclusionsFluctuations in blood glucose levels play a significant role in vascular endothelial dysfunction in type 2 diabetes.Trial registrationUMIN000007581

Glycemic fluctuation and endothelial function in patients of coronary heart disease complicated with type 2 diabetes mellitus

Objective To investigate the glycemic fluctuation and endothelial function in patients of coronary heart disease complicated with type 2 diabetes mellitus (T2DM).Methods Fifty eight patients with coronary heart disease were enrolled in the study,including 40 cases complicated with T2DM (group A) and 18 cases without T2DM (group B).All subjects underwent continuous glucose monitoring system (CGMS) and high-resolution ultrasound detection on brachial artery for endothelium-dependent flowmediated dilatation (FMD).According to the results of CGMS,patients with 3 times of standard deviation of blood glucose (SDBG) less than a mean blood glucose in group A were classified as low glucose excursion group (group A1 ),others were classified as high glucose excursion group (group A2 ).The association of glucose fluctuation with FMD in group A was analyzed.Results Compared to group B,the levels of mean amplitude of glycemic excursions (MAGE),the largest amplitude of glycemic excursions (LAGE) and mean postprandial glucose excursion (MPPGE) were elevated and the levels of FMD were lower in group A1 and A2 (P ＜0.05).Compared to group A1 the levels of MAGE,LAGE,MPPGE and absolute means of daily differences were significantly higher [(5.4 ±0.9) vs.(3.7±0.4),(6.3 ± 1.8) vs.(4.6 ±0.8),(4.7±1.0) vs.(3.5±1.2),(2.45 ±0.75) vs.(1.81 ±0.66)mmol/L,respectively]and the FMD levels were lower [ (3.2 ± 1.0) vs.(5.2 ± 1.2) ％ ]in group A2 ( all P ＜ 0.05 ).All CGMS parameters were significantly correlated with FMD in group A2 (P ＜ 0.05 ).Multiple stepwise regression analysis showed that MAGE,systolic blood pressure were the independent impact factors of FMD.Conclusions Patients of coronary heart disease complicated with T2DM have prominent glycemic fluctuation and decreased FMD and the glycemic fluctuation may be associated with the impairment of FMD. Key words: Coronary disease; Diabetes mellitus, type 2; Glucose fluctuation; Vasodilation

Impact of Glycemic and Blood Pressure Variability on Surrogate Measures of Cardiovascular Outcomes in Type 2 Diabetic Patients

OBJECTIVEThe effect of glycemic variability (GV) on cardiovascular risk has not been fully clarified in type 2 diabetes. We evaluated the effect of GV, blood pressure (BP), and oxidative stress on intima-media thickness (IMT), left ventricular mass index (LVMI), flow-mediated dilation (FMD), and sympathovagal balance (low frequency [LF]/high frequency [HF] ratio) in 26 type 2 diabetic patients (diabetes duration 4.41 ± 4.81 years; HbA1c 6.70 ± 1.25%) receiving diet and/or metformin treatment, with no hypotensive treatment or complications.RESEARCH DESIGN AND METHODSContinuous glucose monitoring (CGM) data were used to calculate mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA)-2, mean blood glucose (MBG), mean postprandial glucose excursion (MPPGE), and incremental area under the curve (IAUC). Blood pressure (BP), circadian rhythm, and urinary 15-F2t-isoprostane (8-iso-prostaglandin F2α [PGF2α]) were also evaluated. Subjects were divided into dipper (D) and nondipper (ND) groups according to ΔBP.RESULTSIMT and LVMI were increased in ND versus D (0.77 ± 0.08 vs. 0.68 ± 0.13 [P = 0.04] and 67 ± 14 vs. 55 ± 11 [P = 0.03], respectively). MBG, MAGE, and IAUC were significantly associated with LF/HF ratio at night (r = 0.50, P = 0.01; r = 0.40, P = 0.04; r = 0.41, P = 0.04, respectively), MPPGE was negatively associated with FMD (r = −0.45, P = 0.02), and CONGA-2 was positively associated with LVMI (r = 0.55, P = 0.006). The Δsystolic BP was negatively associated with IMT (r = −0.43, P = 0.03) and with LVMI (r = −0.52, P = 0.01). Urinary 8-iso-PGF2α was positively associated with LVMI (r = 0.68 P < 0.001).CONCLUSIONSAn impaired GV and BP variability is associated with endothelial and cardiovascular damage in short-term diabetic patients with optimal metabolic control. Oxidative stress is the only independent predictor of increased LV mass and correlates with glucose and BP variability.

Correlation between the Amplitude of Glucose Excursion and the Oxidative/Antioxidative System in Subjects with Different Types of Glucose Regulation

Objective To investigate effects of glucose excursion on the oxidative/antioxidative system in subjects with different types of glucose regulation. Methods A total of 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR) and 27 subjects with newly diagnosed type 2 diabetes mellitus (T2DM) were selected and recruited for 3 days' continuous glucose monitor system (CGMS) assessment. The data from CGMS was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), area under the ROC curve when the blood glucose >5.6 mmol/L within 24 h (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE). In all groups, the content or activity of malondialdehyde (MDA), total antioxidation capacity (TAOC) and glutathione peroxidase (GSH-Px) were detected. Results Glucose excursion parameters of subjects with T2DM or IGR were higher than those of NGR subjects ( P<0.05 or 0.01). Moreover, Glucose excursion parameters of T2DM subjects were higher than those of IGR subjects ( P<0.05 or 0.01). Subjects with T2DM or IGR had significant higher MDA levels and lower GSH-Px/MDA and TAOC/MDA levels compared to NGR subjects ( P<0.01). T2DM subjects had even higher MDA levels and lower GSH-Px/MDA levels than IGR ( P<0.05 or 0.01). According to the median of normal population for MAGE, T2DM and IGR subjects were divided into MAGE>2.6mmol/L Group and MAGE ≤ 2.6mmol/L Group. MAGE>2.6mmol/L Group had higher levels of MDA and lower levels of GSH-Px/MDA than MAGE ≤ 2.6mmol/L Group ( P<0.05). There was no significant difference between the two groups ( P>0.05) in terms of the levels of TAOC/MDA. Pearson correlation analysis showed that MDA was positively correlated with FPG, 2hPG, MAGE, and SBP. GSH-Px/MDA was negatively correlated with MAGE and TC. TAOC/MDA was negatively correlated with FPG. Partial correlation analysis showed that the relationship between MDA and MAGE, GSH-Px/MDA, and MAGE remained significant after adjustments for the other differences among groups. Conclusion Glucose excursion contributed significantly to promoting lipid peroxidation and decreasing antioxidation capacity than chronic sustained hyperglycemia did in the subjects with different types of glucose regulation.

Relationships between glucose excursion and the activation of oxidative stress in patients with newly diagnosed type 2 diabetes or impaired glucose regulation

The effect of glucose excursions on oxidative stress is an important topic in diabetes research. We investigated this relationship by analyzing markers of oxidative stress and glycemic data from a continuous glucose monitoring system (CGMS) in 30 individuals with normal glucose regulation (NGR), 27 subjects with impaired glucose regulation (IGR), and 27 patients with newly diagnosed type 2 diabetes (T2DM). We compared the mean amplitude of glycemic excursion (MAGE), mean postprandial glucose excursion (MPPGE), and mean postprandial incremental area under the curve (IAUC) with plasma levels of oxidative stress markers 8-iso-PGF2α, 8-OH-dG, and protein carbonyl content in the study subjects. Patients with T2DM or IGR had significantly higher glucose excursions and plasma levels of oxidative stress markers compared to normal controls (P < 0.01 or 0.05). Multiple linear regression analyses showed significant relationships between MAGE and plasma 8-iso-PGF2α, and between MPPGE and plasma 8-OH-dG in patients with IGR or T2DM (P < 0.01 or 0.05). Furthermore, 2h-postprandial glucose level and IAUC were related to plasma protein carbonyl content in the study cohort including T2DM and IGR (P < 0.01). We demonstrate that glucose excursions in subjects with IGR and T2DM trigger the activation of oxidative stress.

Correlation between the amplitude of glucose excursion and plasma 8-iso prostaglandin F2alpha level in subjects with different types of glucose regulation

To investigate the effect of glucose excursion on oxidative stress that is expressed by plasma 8-iso prostaglandin F2alpha (8-iso) level. Continuous glucose monitor system (CGMS) was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), mean 1 h preprandial glucose value (1 h-prePG) and 3 h post-prandial glucose value (3 h PPG) over 24 h period, area under the ROC curve when the blood glucose within 24 h > 5.6 mmol/L (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE) on 33 individuals with normal glucose regulation (NGR), 25 subjects with impaired glucose regulation (IGR), and 25 patients with newly diagnosed type 2 diabetes mellitus (T2DM) for 3 days. Plasma 8-iso level was determined by EIA. The plasma 8-iso level of the T2DM patients was 230 ng/L, significantly higher than that of the subjects with IGR (199 ng/L, P < 0.05) and that of the NGR subjects (156 ng/L, P < 0.01). Patients with T2DM also had higher levels of glycated hemoglobin (HbA1c), MBG, SDBG, 1 h pre-PG and 3 h PPG, MAGE, and MODD than those of the NGR and IGR subjects (P < 0.05 or 0.01). The plasma 8-iso level and parameters of glucose excursion of the IGR subjects were all significantly higher than those of the NGR individuals (P < 0.05 or 0.01). Plasma 8-iso level was positively correlated with MAGE, MBG, SDBG, 1 h pre-PG, 3 h PPG, MODD, and HbA1c in all groups. Further analysis showed that the relationship between plasma 8-iso level and MAGE remained significant after adjustment for the other parameters of glucose excursion in multiple linear regression analysis (multiple R(2) = 0.55 for the model including MAGE). Standardized regression coefficients were 0.694 (P = 0.000) for MAGE. Glucose excursion exhibits a stronger triggering effect on oxidative stress than chronic sustained hyperglycemia in the subjects with IGR and T2DM.