| | Efficacy of continuous glucose monitoring system (CGMS) to detect postprandial hyperglycemia and unrecognized hypoglycemia in type 1 diabetic patientsReceived 9 September 2005; accepted 12 May 2006. published online 28 June 2006. Abstract BackgroundTo evaluate the efficacy of continuous glucose monitoring system (CGMS) to detect postprandial hyperglycemia and unrecognized hypoglycemia in type 1 diabetes mellitus (DM1) patients. ConclusionsThe CGMS showed to be a good method to identify postprandial hyperglycemia, to improve therapeutics management and confirmed the low sensitivity of CGMS to detect unrecognized hypoglycemia in DM1 patients. 1. Introduction  The major inconvenience of self-monitoring of blood glucose (SMBG) in clinical practice is due to the fact that blood glucose is only intermittently measured by fingerstick capillary glycemia (CG) from which only a partial and, therefore, incomplete picture of blood glucose fluctuations can be made [1], [2]. Because of many factors, including pain and inconvenience, many patients with diabetes do not accept frequent fingersticks for SMBG [3], including just 10% of the patients submitted to eight point fingerstick by 3 days during continuous glucose monitoring system (CGMS) complete this recommendation. The Diabetes Control and Complications Trial (DCCT) established that intensive and multidisciplinary treatment of type 1 diabetes mellitus (DM1) improved metabolic control and reduces the complications of disease [4]. Psychological aspects and patient's acceptance of DM1 may exercise some influence in their glycemic control [5]. Despite an excellent A1c levels and target preprandial glucose levels, type 1 diabetic patients often experience asymptomatic hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring [6], [7]. In addition, families frequently do not measure blood glucose levels during the night and 55% of severe hypoglycemic events in the DCCT occurred during sleep [8]. Several studies demonstrated the utility of the continuous glucose monitoring system to improve metabolic control, to detect more glycemic excursions (hypo and hyperglycemia) and to detect more postprandial hyperglycemia than SMBG [7], [9], [10], [11], [12], [13]. The efficacy of CGMS in detecting hypoglycemia is not well established in medical literature [7], [14], [15], [16]. This study aimed to determine the accuracy of CGMS and the efficacy of this method to detect unrecognized hypoglycemia and postprandial hyperglycemia in DM1 patients. The complications of CGMS in this population are still discussed. 2. Subjects and methods 2.3. Procedure All patients were submitted to basic orientations of CGMS function and the register of all events in “patient diary”, by one person (F.F.R.M). During the CGMS, all participants had to perform at least four capillary glycemic tests per day and enter these values into the CGMS monitor to obtain correlation coefficients between the SMBG and the CGMS values. All SMBG tests were performed using the digital glucometer (Accu-Chek Active; Roche Diagnosis). The first capillary glycemia entered in the monitor were realized after 60 min of CGMS. Families were asked not to change their dietary practices during the study. It were analyzed: mean CG and mean CGMS sensor's glycemic value; glycemic excursions; postprandial hyperglycemia (NR<140mg/dl); unrecognized hypoglycemia; complications (trauma, local infection, disconnection); dropped the method; therapeutic management after CGMS. Correlation coefficient during hypo, hyper and normoglycemia and sensitivity/specificity were determined. Mean absolute differences (MAD's) were assessed and a Clark error grid was constructed. The glycemic excursions were based on patient's information and correlated by CGMS register. Hypo and hyperglycemia were defined as blood glucose<70mg/dl and >180mg/dl, respectively. The duration of hypo, hyper and normoglycemia were registered in hours/percent for comparison effect. The postprandial hyperglycemia was considered when blood glucose values were over than 140mg/dl 2h after lunch. The hypoglycemic crises were registered by glycemia<70mg/dl and unrecognized hypoglycemia when no clinical symptoms were presented. The choice of blood glucose<70mg/dl as a cut-off for hypoglycemia was based on the fact that poorly controlled DM1 patients often experimented clinical manifestations of hypoglycemia under this level according to medical literature and previous studies with CGMS [7], [17], [18]. There was no consensus in literature about this value for hypoglycemia during CGMS analysis (50–70mg/dl) [6], [7], [17], [18], [19], [20]. The accuracy of CGMS sensor was based on comparison of capillary glycemic values and sensor's values by the T-test during hypo, normo and hyperglycemia, with p value<0.05. The sensitivity and specificity of sensor's value for hypo, hyper and normoglycemia were determined by statistical analysis. The complications during the CGMS were based in medical observation and patient's information. It were analyzed the complications during the sensor implantation (bleeding and pain) and during the exam (trauma, local infection, disconnection, psychological aversion, technical deficiency, others “alarms”), dropped of the method and therapeutic management after CGMS. 2.4. Statistics The data were collected and analyzed by Minitab software, by T-test, Qui-square (χ2) test and regression test. It was considered significant a p value<0.05. 3. Results The number of glucose readings during CGMS was 837.3±235.6 (VR>680), with significant value in 92% of patients. The mean number of hours per sensor was 69.1±10.5h. The mean capillary glucose values were 191.8±46.2mg/dl versus 190.9±42.1mg/dl by CGMS sensor, with no statistical significance detected by T-test (T=−0.6; p=0.9). MAD was 13.6±3.5% (NR<28%) for CGMS. Ninety-six percent of paired non calibration samples were in the clinically acceptable zones of the Clark error grid and 98% in a consensus grid. About the glycemic excursions, the CGMS was significantly more efficient in detection of glycemic excursion related to capillary glycemia (13.4±4.4 versus 10.0±4.2; p=0.001). The postprandial hyperglycemia was identified in 76.9% of type 1 diabetic patients with mean value of 172.2±50.8mg/dl (NR<140mg/dl). The unrecognized hypoglycemia was detected in 58.2% of these patients (Fig. 1). During the 72h CGMS, the patients were in state of hyper, hypo and normoglycemia during 9.7±8.7, 46.2±20.9 and 43.2±18.6% of the register, respectively. The correlation of blood glucose values and CGMS sensor's value during hypoglycemia showed low rate of concordance and presented no statistical significance (p=0.16) versus during hyperglycemia (p=0.002) (Fig. 2) or normoglycemia (p=0.05). The CGMS sensor presented low sensitivity (79.1%) and high specificity (97.5%) to detect hypoglycemia versus during hyper and normoglycemic state (Table 1). | | |  | Glycemic state | Sensitivity (%) | Specificity (%) | p Value | |
|---|
| Hypoglycemia | 79.1 | 97.5 | 0.16 | | | Normoglycemia | 94.5 | 93.2 | 0.05 | | | Hyperglycemia | 96.8 | 95.4 | 0.002 | | | | |
No complications were registered in 94% of patients. The disconnection sign was the most common in this case (10.1%). No trauma, local infection, allergy, bleeding or other was registered during CGMS in this study. The psychological aversion and technical deficiency were not observed in this population. All patients (100%) completed the CGMS integrally. The therapeutic management in DM1 patients was changed in 100% of patients, including insulin adjust dose, change of insulin type, institute nutritional and psychology support and physical activity approach. 4. Discussion In the present study, the CGMS showed some decline in A1c after 3 months in DM1 patients, in agreement to Ludvigsson and Hanas [16]. In this data, we observed a total adherence to CGMS, with no interruption during the procedure. This data showed high accuracy of CGMS versus capillary glycemia, similar to medical literature [9], [10], [11], [12], [13]. Sachedina and Pickup (2003) demonstrated the correlation of sensor's and fingerstick's values in 18 DM1 patients submitted to 72h CGMS. The CGMS showed to be better than intensive CG (eight times per day) in detection of asymptomatic hypoglycemia and postprandial hyperglycemia, in agreement with our data [7], [21]. In pediatric patients, the CGMS showed to be a very safe method and an important alternative to promote decrease of A1c levels, therapeutic adjustment, education and motivation of patients [22], [23]. In EUA, 12 diabetic adolescents (A1c>8%) were studied and submitted to 72h CGMS. The CGMS promoted detection of glycemic excursions in all patients, postprandial hyperglycemia in 10/12 cases and nocturnal hypoglycemia in 30% patients. After 2 months, they observed a significant decrease of A1c levels [6], [24], [25]. About the CGMS sensor efficacy in detecting glycemic excursions, these results corroborated to many studies in medical literature [26], [27], [28]. This data showed that CGMS is very useful to detect postprandial hyperglycemia. Recent data of 91 DM1 patients estimated that the accuracy of CGMS sensor is more effective in elevated glycemic levels than hypoglycemic state [26], in agreement to our data. The efficacy of CGMS in detecting hypoglycemia is not well established in medical literature [7], [14], [15], [29]. Boland et al. (2001) detected unrecognized hypoglycemia in 70% of 56 type 1 diabetic children submitted to 72h CGMS and considered this method a gold standard in hypoglycemia management in pediatric population underwent only to SMBG even if they have A1c<7.0% [27]. Kovatchev et al. (2004) revealed that the accuracy of sensor readings were lower in hypoglycemia (73.5%) versus euglycemia (99%) and hyperglycemia (95.4%), with failure to detect hypoglycemia like the most common error during the test [14]. In this data, the correlation between capillary glucose and sensor's glucose values during hypoglycemia showed no significance, with low sensitivity of CGMS sensor for hypoglycemic state, corroborating value to McGowan et al. [15], Guerci et al. [23], and Kovatchev et al. [14]. An recent study with 200 children, showed similar results with this when compared eight point glucose testing per day against CGMS. They observed that only 10% of the patients complete full fingerstick tests during 3 days. This group observed more efficacies of CGMS in detecting postprandial hyperglycemia and low sensitivity of CGMS sensor to detect hypoglycemia, in order to corroborate our data [29]. Chico et al. (2003) reported the usefulness of CGMS in detecting unrecognized hypoglycemia and improving metabolic control in 70 diabetic patients submitted to 72h CGMS. The CGMS detected unrecognized hypoglycemia in 62.5% of the type 1 diabetic patients and in both were observed significant decrease levels of A1c after 3 months, similar to our data [28]. About the complications of CGMS, no trauma, local infection or bleeding were registered. The insulin therapeutic regimen was adjusted in 100% of DM1 patients. In Guerci et al. analyses, the disconnection was the most common problem detected during CGMS, without any side effects reported at the site of sensor implantation [23]. In this data, all the patients completed at least 4 fingerstick values entered to the monitor, promoting high accuracy of CGMS values. 5. Conclusions This study suggests that CGMS is a very good method to identify glycemic excursions, postprandial hyperglycemia and to improve metabolic changes in therapeutics of type 1 diabetic patients. The CGMS is a very safe method, well tolerated by patients, with low accuracy in detecting hypoglycemic state. 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a Department of Physiology, Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil b Department of Endocrinology and Metabolism, Hospital Universitário São José, Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil  Corresponding author. Tel.: +55 31 3296 3345; fax: +55 31 3283 9772.
PII: S0168-8227(06)00196-3 doi:10.1016/j.diabres.2006.05.009 © 2006 Elsevier Ireland Ltd. All rights reserved. | |
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