Mean Amplitude Of Glucose Excursions Research Articles

Analysis on blood glucose excursion in men with nonalcoholic fatty liver disease

Forty-eight men with normal glucose tolerance were divided into fatty liver disease ( NAFLD, n =23 ) and non-NAFLD (n =25 ) groups. The blood glucose excursion was evaluated by continuous glucose monitoring system. The results showed that the mean amplitude of glucose excursion[MAGE, (2. 17± 1.13 vs 1.45±0. 42 )mmol/L]and standard deviation of blood glucose[SDBG, (0. 88 ±0. 45 vs 0. 61 ±0. 21 ) mmol/L]were significantly higher in NAFLD group than in non-NAFLD group( both P＜0. 05 ). MAGE and SDBG were positively correlated with body mass index, waist circumference, and the increased value of plasma glucose 0. 5 h after glucose loading( △G30,all P＜0. 05 ). In multiple regression analysis, △G30, waist circumference, and age were significant independent predictors for MAGE( P＜0. 05 or P＜0. 01 ). △G30 and waist circumference were significant independent predictors for SDBG( P＜0. 05 or P＜0. 01 ). Key words: Nonalcoholic fatty liver disease ; Blood glucose excursion; Male

Comparison Between Sensor-Augmented Insulin Therapy with Continuous Subcutaneous Insulin Infusion or Multiple Daily Injections in Everyday Life: 3-Day Analysis of Glucose Patterns and Sensor Accuracy in Children

Sensor-augmented continuous subcutaneous insulin infusion (CSII) therapy is superior to CSII therapy alone, but little is known on the effectiveness of sensor-augmented multiple daily injections (MDI) therapy. We compared during everyday life mean glucose control and several variability indexes recorded for 3 days by a real-time glucose sensor (Medtronic, Northridge, CA) in two groups of children treated with either CSII or MDI. Fifty-five consecutive subjects were examined: 17 receiving CSII and 38 receiving MDI basal-bolus therapy (age range, 7-22 years). All subjects wore the sensor for 4 days, and 3 days were used for statistical analysis. Mean glucose and SD, coefficient of variation (CV), mean amplitude of glucose excursion (MAGE), mean of daily differences (MODD), continuous overall net glycemic action (CONGA) at 2 and 4 h, blood glucose (BG) rate, area under the curve (AUC) above 180 mg/dL and below 70 mg/dL, Low BG Index (LBGI), and High BG Index (HBGI) were calculated. Patients receiving CSII administered more daily boluses than patients receiving MDI (5.2±1.5 vs. 3.2±0.3, respectively; P=0.001). Mean glucose was lower in the CSII group. AUC above 180 mg/dL and HBGI were higher in the MDI group. CV, CONGA at 2 h, CONGA at 2 h during the day, and HBGI were worse in the MDI group, whereas MODD, LBGI, BG rate, and MAGE were similar. A positive correlation (r=0.95; P<0.05) was found between the paired sensor-meter values. For the glucose values <70 mg/dL, sensitivity was 40%, and specificity was 99%. In our pediatric patients during everyday life sensor-augmented CSII therapy seemed more effective than sensor-augmented MDI therapy, in terms both of glucose mean values and of intraday variability. Mild hypoglycemic episodes and indexes of low BG values were similar in the two groups, although the latter results may be inaccurate because of low sensor sensitivity at low glucose value.

Safety, Pharmacokinetic, and Pharmacodynamic Profiles of Ipragliflozin (ASP1941), a Novel and Selective Inhibitor of Sodium-Dependent Glucose Co-Transporter 2, in Patients with Type 2 Diabetes Mellitus

The sodium-dependent glucose co-transporter 2 (SGLT2) is a high-capacity, low-affinity transport system primarily expressed in the renal proximal tubules, where it plays an important role in the regulation of glucose levels. Inhibition of SGLT2 represents an innovative approach for plasma glucose control in type 2 diabetes mellitus (T2DM) by blocking glucose reabsorption and enhancing glucose loss in the urine. This Phase 2, randomized, placebo-controlled study investigated the safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of the novel oral SGLT2 inhibitor ipragliflozin (ASP1941) in T2DM patients. Sixty-one patients were randomized to placebo or ipragliflozin once daily at doses of 50, 100, 200, or 300 mg for 28 days. Patients were admitted to the clinic during the study and received a weight-maintenance diet. The incidence of treatment-emergent adverse events was similar for placebo and ipragliflozin groups. There were no deaths, and no patients discontinued ipragliflozin because of adverse events. Ipragliflozin was absorbed rapidly, taking approximately 1 h to reach the maximum concentration. The area under the concentration-time curve and maximum ipragliflozin concentration at steady state displayed dose linearity. All ipragliflozin doses significantly reduced glycosylated hemoglobin, fasting plasma glucose, and mean amplitude of glucose excursions compared with placebo. Significant dose-dependent increases in urinary glucose excretion were observed in all ipragliflozin groups. Mean weight decreased in the placebo and ipragliflozin groups, with greater reductions occurring in ipragliflozin-treated patients. Ipragliflozin was generally safe, well tolerated, and effective at blocking renal glucose reabsorption and decreasing plasma glucose levels in T2DM patients.

Glycemic Variability in Abdominally Obese Men With Normal Glucose Tolerance as Assessed by Continuous Glucose Monitoring System

The purpose of this study was to observe both the glycemic variability in abdominally obese men with normal glucose tolerance (NGT) and the relationship between glycemic variability and early atherosclerosis. This case-control study included 23 abdominally obese men (waist circumference (WC) ≥90cm) and 23 nonabdominally obese men (WC <90cm) with NGT who were between 20 and 50 years of age. All subjects were of the Han ethnicity. The cases and controls were age-matched. A continuous glucose monitoring system (CGMS) was used in this study. With the CGMS, the standard deviation of blood glucose (SDBG) and the mean amplitude of glucose excursion (MAGE) were calculated to estimate glycemic variability. The carotid intima-media thickness (CIMT) was used as a surrogate marker of early atherosclerosis. Mean blood glucose (MBG) (6.13 ± 0.94 vs. 5.55 ± 0.87mmol/l), SDBG (0.89 ± 0.34 vs. 0.64 ± 0.24mmol/l), MAGE (2.05 ± 0.83 vs. 1.57 ± 0.52mmol/l), and CIMT (0.73 ± 0.12 vs. 0.67 ± 0.05mm) were significantly higher in the abdominally obese men than in the nonabdominally obese men (P < 0.05). WC positively correlated with MBG (r = 0.302, P = 0.041), SDBG (r = 0.362, P = 0.013), MAGE (r = 0.302, P = 0.041), and CIMT (r = 0.487, P = 0.001). CIMT did not correlate with MBG (r = 0.206, P = 0.169), SDBG (r = 0.114, P = 0.450), and MAGE (r = 0.085, P = 0.574). After multivariate analysis, WC was still significantly associated with MBG (β = 0.025, P = 0.041), SDBG (β = 0.010, P = 0.013), MAGE (β = 0.019, P = 0.042), and CIMT (β = 0.008, P = 0.022). This study demonstrates that glycemic variability is increased in abdominally obese men with NGT. A relationship between glycemic variability and atherosclerosis was not observed in this study and requires further investigation.

Comparison of daily glucose excursion by continuous glucose monitoring between type 2 diabetic patients receiving biphasic insulin aspart 30 or biphasic human insulin 30

Aims/Introduction: Biphasic insulin aspart 30 (BIAsp 30) has an earlier and stronger peak effect with a similar duration of action to biphasic human insulin 30 (BHI 30). However, direct comparison of daily glucose excursion during treatment with these two types of insulin has not been carried out. We carried out continuous glucose monitoring (CGM) and evaluated the 48-h glucose profile during twice-daily injections of BIAsp 30 or BHI 30 at the same dosage in 12 hospitalized patients with type 2 diabetes who participated in a randomized cross-over trial. The 48-h average glucose level and mean amplitude of glucose excursion (MAGE) were lower during BIAsp 30 treatment than with BHI 30. The average glucose level during 2-3 h after breakfast and 2-4 h after dinner, and the incremental postprandial glucose from just before to 4 h after dinner were lower with BIAsp 30 treatment than with BHI 30. Furthermore, BIAsp 30 treatment reduced the SD from 30 min before to 4 h after breakfast and lunch compared with BHI 30. The average glucose level and SD during the 30 min before each meal and during the night were not different between the two insulin preparations, and hypoglycemia was not observed with either treatment. Twice-daily BIAsp 30 reduced the 48-h average glucose and MAGE, the postprandial glucose (after breakfast and dinner), and the SD of glucose excursion (after breakfast and lunch) compared with the same dosage of BHI 30, without causing hypoglycemia or deterioration of glycemic control before meals and at night. This trial was registered with UMIN (no. UMIN000005129). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00123.x, 2011).

High Glycemic Variability Assessed by Continuous Glucose Monitoring After Surgical Treatment of Obesity by Gastric Bypass

Obesity surgery elicits complex changes in glucose metabolism that are difficult to observe with discontinuous glucose measurements. We aimed to evaluate glucose variability after gastric bypass by continuous glucose monitoring (CGM) in a real-life setting. CGM was performed for 4.2 ± 1.3 days in three groups of 10 subjects each: patients who had undergone gastric bypass and who were referred for postprandial symptoms compatible with mild hypoglycemia, nonoperated diabetes controls, and healthy controls. The maximum interstitial glucose (IG), SD of IG values, and mean amplitude of glucose excursions (MAGE) were significantly higher in operated patients and in diabetes controls than in healthy controls. The time to the postprandial peak IG was significantly shorter in operated patients (42.8 ± 6.0 min) than in diabetes controls (82.2 ± 11.1 min, P = 0.0002), as were the rates of glucose increase to the peak (2.4 ± 1.6 vs. 1.2 ± 0.3 mg/mL/min; P = 0.041). True hypoglycemia (glucose <60 mg/dL) was rare: the symptoms were probably more related to the speed of IG decrease than to the glucose level achieved. Half of the operated patients, mostly those with a diabetes background before surgery, had postprandial glucose concentrations above 200 mg/dL (maximum IG, 306 ± 59 mg/dL), in contrast to the normal glucose concentrations in the fasting state and 2 h postmeal. Glucose variability is exaggerated after gastric bypass, combining unusually high and early hyperglycemic peaks and rapid IG decreases. This might account for postprandial symptoms mimicking hypoglycemia but often seen without true hypoglycemia. Early postprandial hyperglycemia might be underestimated if glucose measurements are done 2 h postmeal.

The accuracy of real-time continuous monitoring system at different stages and its association with glucose excursion

Objective To study the accuracy of real-time continuous monitoring system (RT-CGMS) at different stages and its association with glucose excursion. Methods Totally 33 patients with type 1 diabetes or type 2diabetes were under surveillance of RT-CGMS for 5 d. Capillary glucose values were measured 7 times daily.Correlation coefficient, error grid analysis (EGA), and Bland-Altman analysis methods were used to assess the correlation, accuracy and agreement of RT-CGMS at different stages and in general level; The mean amplitude of glucose excursion (MAGE) and the frequency of glucose excursion ( FGE ) were also calculated. Results ( 1 ) The correlation coefficient of RT-CGMS with capillary glucose values at fasting, postprandial stages, and in general level were 0.94,0.92, and 0.93 respectively( P＜0.01 ). (2) EGA showed that 98.82%, 98.39%, and 98.64% of the results fell in the A and B zones and 1. 18%, 1.61%, and 1.36% fell in the D zone respectively at fasting,postprandial stages, and in general level. There is no result fell in C and E zones. ( 3 ) The agreement analysis showed that RT-CGMS readings were in close agreement with capillary glucose values at fasting, postprandial periods, and in general level. (4)The MAGE at fasting, postprandial periods, and in general level were (3.57±2.66), (4.07±3.09), and (4. 02 ±3.04) mmol/L (P＞0. 05), (0±0. 5), (3± 1), and( 1 ±3) d for FGE (P＜0. 01 ).Conclusion RT-CGMS at fasting stage has higher accuracy than postprandial stage and general level, FGE at fasting stage is higher than postprandial stage and general level. Key words: Real-time continuous monitoring system; Fasting periods; Postprandial periods; Accuracy; Glucose excursion

Effects of a low-carbohydrate diabetes-specific formula in type 2 diabetic patients during tube feeding evaluated by continuous glucose monitoring

summary Background & aims: In type 2 diabetic patients with dysphagia as a sequela of cerebrovascular accident, enteral nutrition tube feeding, especially with high-carbohydrate (CHO) standard formulas, may lead to acute glucose variation (GV). We assessed whether a low-CHO, diabetes-specific formula improves GV over 24 h using continuous glucose monitoring (CGM). Methods: Patients were fed either a low-CHO, diabetes-specific formula (henceforth, low-CHO formula) or a high-CHO standard formula (henceforth, high-CHO formula) for 2 days. Blood glucose (BG) was assessed by CGM throughout the observation period. Results: Ten patients who received enteral tube feeding with the low-CHO formula had significantly (p < 0.01) lower 24-h mean BG than patients fed a high-CHO formula (123.2 � 38.3 vs. 143.7 � 58.1 mg/ dL). Mean amplitude of glucose excursion was significantly (p < 0.01) lower in the low-CHO vs. high-CHO formula group, as was 24-h GV (p < 0.05). Percent period of hyperglycemia was significantly (p < 0.05) reduced when patients were fed low-CHO vs. high-CHO formula (16.8 � 31.5% vs. 37.9 � 33.0%); hypoglycemia was rarely observed. Conclusions: A low-CHO formula may enhance postprandial and fasting BG profiles and alleviate GV. It may therefore be useful for diabetic patients requiring enteral tube feeding.

Effects of a novel short-term continuous subcutaneous insulin infusion program evaluated by continuous glucose monitoring on young adult type 1 diabetic patients in Taiwan

The aim of this study is to evaluate the effectiveness of blood sugar control by a short-course reinforcement program, consisting of using continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) for young adult type 1 diabetic patients. Twenty-six pump-naïve type 1 diabetic patients were successively enrolled in two years. The mean disease duration was 13 years and the mean HbA1c was 8.8 %. Initially, a 3-day course of CGM was used to evaluate the baseline glycemic status of the subjects, followed by 6-day intensive insulin adjustment by CSII therapy. Thereafter, a second course of CGM was performed to evaluate the effectiveness of our outcomes in comparison to the initial measurements. All participants received necessary education and instruction as required throughout the course of the program. The glucose variability as measured by standard deviation of plasma glucose and mean amplitude of glucose excursion decreased significantly (67.8 ± 2.7 to 52.0 ± 1.8 mg/dL and 140.4 ± 6.5 to 105.5 ± 5.3 mg/dL, p < 0.001). The hypoglycemic events noted per patient were reduced by 46.4% (p = 0.003) and occurred significantly less often during nocturnal periods (-63.2%, p = 0.002). Following the adjustment, the mean daily insulin requirement was reduced by 28.05% (from 0.82 to 0.59 IU/kg) and the new proportion of 40% as basal insulin was found. The short-term CSII program provided significant improvement in blood sugar control for type 1 diabetic patients, by reducing hypoglycemic events, glucose excursion, and insulin dosage in our examined subjects.

Correlation of real-time continuous monitoring system with venous glucose and capillary glucose values

To study the correlation of real-time continuous monitoring system (RT-CGMS) with venous glucose and capillary glucose values. A total of 33 diabetics received RT-CGMS for 5 days. Fasting venous glucose values were measured at Days 1, 3 and 5 and capillary glucose values recorded 7 times daily. The methods of correlation coefficient, error grid analysis (EGA) and Bland-Altman analysis were employed to assessed the correlation, accuracy and agreement of RT-CGMS with venous glucose and capillary glucose values respectively. The mean amplitude of glucose excursions (MAGE) was calculated during RT-CGMS testing periods. (1) The correlation coefficient of RT-CGMS with vein glucose and capillary glucose values were 0.936, 0.933 (P < 0.01); (2) The analysis results of EGA showed that 98.67%, 98.64% of venous and capillary values fell in the A and B zones and 1.33%, 1.36% fell in the D zone; (3) The agreement analysis showed that RT-CGMS readings were in close agreement with venous glucose and capillary glucose results; (4) The patients at the same MAGE levels had obvious differences in HbA1C. There is a high level of correlation, accuracy and agreement between RT-CGMS and venous glucose and capillary glucose values.

Inter-Day Glycemic Variability Assessed by Continuous Glucose Monitoring in Insulin-Treated Type 2 Diabetes Patients on Hemodialysis

Type 2 diabetes patients on chronic hemodialysis have a high prevalence of cardiovascular complications and often show a poor glycemic control. Single-spot glycemic measurements are not always meaningful, and the hemoglobin A1c (HbA1c) value does not reflect short-term variations in glucose metabolism in this patient category. Therefore, to better understand their metabolic balance, we studied a group of diabetes patients on hemodialysis by a continuous glucose monitoring (CGM) system. Twelve insulin-treated type 2 diabetes patients on hemodialysis were studied by a microdialysis-based subcutaneous glucose sensor over a period of 2 days, including the dialysis day (HD) and the following inter-dialytic period ("free" day [FD]). The mean 24-h glycemic value, the mean amplitude of glucose excursions, and the SD of mean glucose were significantly higher in the HD than the FD (186 ± 50 vs. 154 ± 25 mg/dL, P<0.05; 75 ± 22 vs. 56 ± 15 mg/dL, P<0.05; and 57 ± 6 vs. 35 ± 11 mg/dL, P<0.05, respectively). Considering the 48-h recording, there was a direct correlation between the mean glucose concentration and the HbA1c (r=0.47, P<0.05), whereas no association was observed between the measures of glucose variability and HbA1c. Insulin-treated diabetes patients on hemodialysis showed different glucose profiles between the HD and the FD. In particular, in the HD they have had an increased glycemic variability, which may represent an adjunctive risk factor for cardiovascular complications. Therefore the use of a CGM system, as a means of assessing the measures of glycemic variability, could improve the management of insulin therapy in these patients.

Mixing Insulin Aspart With Detemir Does Not Affect Glucose Excursion in Children With Type 1 Diabetes

OBJECTIVEWe hypothesized that insulin detemir mixed with aspart had equivalent effects on blood glucose as if being given as separate injections in pediatric type 1 diabetes patients.RESEARCH DESIGN AND METHODSFourteen children with type 1 diabetes were randomly assigned to either Study A (mixed insulins) or Study B (separate insulins) for the first 10 days and crossed over for the last 10 days. Each subject underwent continuous glucose monitoring on the last 72 h of each study.RESULTSThe 48-h area under the curve (mmol/hour/l), M-value, and mean amplitude of glucose excursion (mmol/l) for Study A versus Study B were 457 ± 70 versus 469 ± 112 (P = 0.58), 39.67 ± 15.37 versus 39.75 ± 9.69 (P = 0.98), and 6.35 ± 1.92 versus 5.98 ± 0.92 (P = 0.42), respectively.CONCLUSIONSInsulin detemir mixed with aspart had equivalent effects on blood glucose versus giving them as separate injections in children with type 1 diabetes.

Effect of targeting normal fasting glucose levels with basal insulin glargine on glycaemic variability and risk of hypoglycaemia: a randomized, controlled study in patients with early Type 2 diabetes

The purpose of this sub-study of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial was to determine efficacy and safety of targeting normal fasting plasma glucose (FPG) levels in patients with early Type 2 diabetes treated with insulin glargine in comparison with standard care. Participants were randomly allocated to insulin or standard care. Insulin was titrated to reach FPG <or= 5.3 mmol/l. Two years after randomization in a small subset (43 glargine, 32 standard care), continuous glucose measurement (CGMS System Gold), including a test meal, was performed. Sixteen volunteers with normal oral glucose tolerance test (OGTT) served as control subjects. Objectives were glycaemic variability, standard deviation (sd), mean amplitude of glucose excursion (MAGE) with postprandial glucose excursion after the test meal, time spent < 3.0 mmol/l interstitial glucose. Participants allocated to insulin and standard care had FPG levels of 5.3 and 6.1 mmol/l (P = 0.019) and glycated haemoglobin (HbA(1c)) 5.7% and 5.9%, respectively (P < 0.025). Time (min/24 h) spent at low glucose levels was not significantly different between groups (30.6 +/- 83.8 min control subjects, 33.7 +/- 75.1 min insulin, 10.6 +/- 50.6 min standard care). Standard deviation and MAGE were similar for glargine and standard care, but significantly higher than in control subjects. If FPG was < 5.3 mmol/l, the postprandial glucose excursion was in the range seen in control subjects. Treatment to target of FPG < 5.3 mmol/l with insulin glargine was not associated with significantly increased risk of hypoglycaemia. Strict control of FPG with insulin glargine was effective to control postprandial glucose excursion, but had no significant effect on sd and MAGE.

The use of exenatide in severely burned pediatric patients

IntroductionIntensive insulin treatment (IIT) has been shown to improve outcomes post-burn in severely burnt patients. However, it increases the incidence of hypoglycemia and is associated with risks and complications. We hypothesized that exenatide would decrease plasma glucose levels post-burn to levels similar to those achieved with IIT, and reduce the amount of exogenous insulin administered.MethodsThis open-label study included 24 severely burned pediatric patients. Six were randomized to receive exenatide, and 18 received IIT during acute hospitalization (block randomization). Exenatide and insulin were administered to maintain glucose levels between 80 and 140 mg/dl. We determined 6 AM, daily average, maximum and minimum glucose levels. Variability was determined using mean amplitude of glucose excursions (MAGE) and percentage of coefficient of variability. The amount of administered insulin was compared in both groups.ResultsGlucose values and variability were similar in both groups: Daily average was 130 ± 28 mg/dl in the intervention group and 138 ± 25 mg/dl in the control group (P = 0.31), MAGE 41 ± 6 vs. 45 ± 12 (respectively). However, administered insulin was significantly lower in the exenatide group than in the IIT group: 22 ± 14 IU patients/day in the intervention group and 76 ± 11 IU patients/day in the control group (P = 0.01). The incidence rate of hypoglycemia was similar in both groups (0.38 events/patient-month).ConclusionsPatients receiving exenatide received significantly lower amounts of exogenous insulin to control plasma glucose levels. Exenatide was well tolerated and potentially represents a novel agent to attenuate hyperglycemia in the critical care setting.Trial registrationNCT00673309.

Interpretation of Continuous Glucose Monitoring Data: Glycemic Variability and Quality of Glycemic Control

There are a large number of measures of glycemic variability, including standard deviation (SD), percentage coefficient of variation (%CV), interquartile range (IQR), mean amplitude of glucose excursion (MAGE), mean of daily differences (MODD), and continuous overlapping net glycemic action over an n-hour period (CONGA(n)). These are all highly correlated with the overall or "total" SD, SD(T). SD(T) is composed of several components corresponding to within-day variability, between-day variability (between daily means and between days-within specified time points), and the interaction of these sources of variability. We identify several subtypes of SD; each is highly correlated with SD(T). Variability may also depend on time of day. Numerous measures of quality of glycemic control have been proposed, including a weighted average of glucose values (M)(e.g., M(100) is M at 100 mg/dL), a measure of quality of glycemic control based on mean and SD (J), the Glycemic Risk Assessment Diabetes Equation (GRADE), the Index of Glycemic Control (IGC), the High Blood Glucose Index (HBGI), the Low Blood Glucose Index (LBGI), the Average Daily Risk Range (ADRR), and percentage of glucose values within specified ranges. These methods usually but not always give consistent results: they can differ widely in terms of their ability to detect responses to therapeutic interventions. Based on review of the advantages and limitations of these measures and on extensive experience in the application of these methods, we outline a systematic approach to the interpretation of continuous glucose monitoring data for use by clinical researchers and clinicians to evaluate the quality of glycemic control, glucose variability including within- and between-day variability, the day-to-day stability of glycemic patterns, and changes in response to therapy.

Characteristics of glycemic excursion in different subtypes of impaired glucose intolerance

To investigate the characteristics of glycemic excursion of different subtypes of glucose tolerance. Assessed by oral glucose tolerance test (OGTT) repeated twice, 81 individuals were divided into 4 groups: normal glucose tolerance (NGT, n = 18), isolated impaired fasting glycemia (IFG, n = 12), isolated impaired glucose tolerance (IGT, n = 19), combined IFG/IGT (n = 11), and newly diagnosed type 2 diabetes mellitus (T2DM, n = 21). And then continuous glucose monitoring system (CGMS) was used for 72 hours to monitor the blood glucose (BG) level before drug intervention. (1) The levels of largest amplitude of glycemic excursions (LAGE), mean blood glucose (MBG), and standard deviation of mean level of blood glucose fluctuation (SDBG) increased gradually with the deterioration of glucose tolerance. The mean amplitude of glucose excursion (MAGE) readout of the IGT group was (3.2 +/- 1.2) mmol/L, significantly higher than that of the NGT group [(1.6 +/- 0.5) mmol/L, P < 0.05], and significantly lower than that of the T2DM group [(5.2 +/- 1.9) mmol/L, P < 0.05]. The level of frequency of glucose excursion (FGE) decreased along with the decrease of glucose tolerance: NGT group [(6.1 +/- 3.4)] > IGT/IFG group [(5.5 +/- 2.5)] > T2DM group [(4.8 +/- 1.8)]. Among the three components of IGR, the IGT group showed highest MAGE (3.2 +/- 1.2) mmol/L and lowest FGE level (4.9 +/- 1.8). (2) The level of absolute mean of daily difference (MODD) increased in the following order: NGT group [(0.8 +/- 0.3) mmol/L], IGT group [(1.1 +/- 0.4) mmol/L], IFG/IGT group [(1.2 +/- 0.4) mmol/L], and T2DM group [(2.0 +/- 1.0) mmol/L] (all P < 0.05). (3) The fasting glucose level deteriorated the most rapidly in the IFG group, while it reached the highest postprandial peak in the IFG/IGT group. The blood glucose curve increased along the order of NGT, I-IGT, IFG/IGT, IFG, and T2DM. (4) When the level of glycosylated hemoglobin (HbA1c) level was less than 7%, the fasting phase of curve virtually coincided with each other among individual groups with different HbA1c levels; however, the postprandial peak separated slightly. When the HbA1C level was between 7.0% and 7.9%, the postprandial peaks of individual groups with different HbA1c levels dispersed markedly. When the HbA1c level was higher than 8%, the fasting blood glucose curve moved upwards significantly with increasing postprandial excursion. (1) With the deterioration of glucose regulation, the intraday and day-to-day blood glucose excursions become increasingly fluctuant. (2) The amplitude of glycemic excursion is lower in the NGT group than in the T2DM group, however, the frequency of glycemic excursion is higher in the NGT subject than in the T2DM subjects. The glucose excursion profile of the IGR subjects is between the NGR and T2DM subjects. (3) The characteristics of glucose excursion of the IGT group are similar to those of the T2DM group, and the characteristics of the IFG group are similar to those of the NGT group. (4) The loss of postprandial glycemic control precedes evident deterioration in fasting phase of IGR.

Better Postprandial Glucose Stability During Continuous Subcutaneous Infusion with Insulin Aspart Compared with Insulin Lispro in Patients with Type 1 Diabetes

Persistent glucose variability is a frequent condition in type 1 diabetes. Continuous subcutaneous insulin infusion (CSII) is a rational option to overcome this clinical issue; however, no comparative studies have been reported for aspart and lispro insulin when used in CSII. This study compare the effects of aspart and lispro delivered by CSII on glycemic stability as measured using a continuous glucose monitoring system. This single-center, randomized, controlled, 3-day crossover trial included 17 patients with type 1 diabetes. Patients were randomized to receive insulin aspart or insulin lispro. The next day, they received a standard meal at breakfast and lunch and a bolus of insulin aspart or lispro based on insulin:carbohydrate ratio. Patients were monitored for 8 h, after which they received a crossover treatment with insulin aspart or insulin lispro followed by the same procedure as previously. Postprandial blood glucose was more stable with insulin aspart than insulin lispro (absolute Deltaglucose 7.04 +/- 3.16 vs. 9.04 +/- 4.2, P < 0.0019). Daily blood glucose variability profiles (coefficient of variation and mean amplitude of glucose excursion) and frequency of hypoglycemic episodes (area under the curve <72 mg/dL) were similar with both treatments. Postprandial glucose was more stable when insulin aspart was infused as a pre-meal bolus compared with insulin lispro, indicating a more favorable effect of insulin aspart on postprandial glucose. No differences in overall daily glucose stability were observed between insulin aspart and insulin lispro when infused as basal rate insulin.

Relationship between blood glucose variability and microalbuminuria in type 2 diabetic patients with well-controlled glycosylated hemoglobin

To investigate the relationship between the blood glucose variability and microalbuminuria (MAU) in type 2 diabetic patients with well-controlled glycosylated hemoglobin (HbA1c) and the influencing factors of blood glucose variability. One hundred and seventy-six type 2 diabetic patients with HbA1c under 6.5% and 48 subjects with normal glucose regulation were monitored using the continuous glucose monitoring system (CGMS). The mean blood glucose (MBG) and mean amplitude of glucose excursions (MAGE) were analyzed. (1) The MBG and MAGE levels of type 2 diabetic patients were (7.0+/-0.9) and (3.8+/-2.5) mmol/L respectively, both higher than those of the subjects with normal glucose regulation [(5.4+/-0.6) and (2.0+/-0.7) mmol/L respectively, both P<0.01]. (2) The incidence ratio of MAU of the patients with ascended MAGE level was 18.7%, significantly higher of those with normal MAGE (7.1%, P<0.05). (3) The MAGE level was positively correlated with age, duration of diabetes, and systolic blood pressure, and negatively correlated with glomerular filtration rate and the levels of fasting and postprandial C-peptide. Multivariant regression analyses indicated that duration of diabetes and the level of postprandial C-peptide 30 min after meal were the independent influential factors of MAGE. (4) In the type 2 diabetic patients, the MAGE of the MAU group was higher than that of the non-MAU group (P<0.05). Logistic regression analyses indicated that diastolic blood pressure and MAGE were the risk factors of MAU (OR=1.201 and 1.357, both P<0.05). In well-controlled patients with type 2 diabetes, blood glucose variability is one of the risk factors for MAU, duration of diabetes and early stage of insulin secretion function are the main factors influencing glycemic variability.

Group of Signs: A New Method to Evaluate Glycemic Variability

Glycemic variability is an important parameter used to resolve potential clinical problems in diabetic patients. It is known that glycemic variability generates oxidative stress and potentially contributes to the development of macro- and microvascular complications in diabetes. By controlling glycemic variability, it is possible to reduce these complications and to set the therapy for all patients with diabetes. The aims of this study were to (1) propose a new standardized, objective, and flexible approach to measure glycemic variability by a continuous glucose monitoring system (CGMS)-the group of signs (GOS) method; (2) compare the correlation between mean amplitude of glucose excursion (MAGE), a well-known index of glycemic variability calculated by the physician and the MAGE defined with the GOS method, in order to validate the GOS; and (3) suggest new indexes of glycemic variability. We tested the GOS algorithm on data collected by a CGMS every 5 minutes for 24 hours on 50 patients. Consequently, for 8 patients we calculated and compared the physician's MAGE in the standard way and by the GOS method. Comparison between the two methods has shown high correlations, from a minimum correlation of 86% to a maximum of 98%, with p values <0.01 (Pearson test). Preliminary data suggest that the proposed algorithm is a valid, efficient, and reliable method able to calculate the standard MAGE on CGMS data systematically and to create other alternative glycemic variability indexes.

Is glycemic variability important to assessing antidiabetes therapies?

Traditionally, statistical estimation of glycemic variability includes computing standard deviation of glucose readings or related statistics (eg, M value, mean amplitude of glucose excursions, and so forth). We advocate an alternative approach using risk measures of variability, which have substantial clinical and numerical advantages. In addition, continuous glucose monitoring (CGM) data have clinically important inherent temporal structure that should be taken into consideration. Thus, temporal variability methods are discussed for the analysis and interpretation of CGM output.