CGM Metrics Predict Imminent Progression to Type 1 Diabetes: Autoimmunity Screening for Kids (ASK) Study

Objective: Children identified with stage 1 type 1 diabetes are at high risk for progressing to stage 3 (clinical) diabetes and require accurate monitoring. Our aim was to establish CGM metrics that could predict imminent progression to diabetes. <p>Methods: In the Autoimmunity Screening for Kids study, 91 children persistently islet autoantibody positive (median age 11.5 y, 48% non-Hispanic White, 57% female) with a baseline CGM were followed for development of diabetes for a median of 6 (range:0.2-34) months. Of these, 16 (18%) progressed to clinical diabetes in a median of 4.5 (range:0.4-29 months. </p> <p>Results: Compared to non-progressors, progressors had significantly higher average sensor glucose (119 vs 105 mg/dL) and increased glycemic variability: SD 27 vs 16, CV 21 vs 15, MODD 24 vs 16 and MAGE 43 vs 26. Progressors spent 21% of <a>time above 140 mg/dl </a>(TA140) and 8% above 160 mg/dl, compared to 3% and 1%, respectively, for non-progressors. <a>In survival analyses, the risk of progression to diabetes in one year was 80% in those with TA140 >10%; in contrast, it was only 5% in the other participants. </a><a>Performance of prediction by receiver operating curve analyses showed area under the curve of <u>></u>0.89 for both individual and combined CGM metric models</a>. </p> <p>Conclusions<a>: </a><a>TA140 >10% is associated with a high risk of progression to clinical diabetes within the next year</a> in autoantibody positive children. CGM should be included in the ongoing monitoring of high-risk children<a></a><a> a</a>nd could be used as potential entry criteria for prevention trials. </p>

CGM Metrics Predict Imminent Progression to Type 1 Diabetes: Autoimmunity Screening for Kids (ASK) Study

Objective: Children identified with stage 1 type 1 diabetes are at high risk for progressing to stage 3 (clinical) diabetes and require accurate monitoring. Our aim was to establish CGM metrics that could predict imminent progression to diabetes. <p>Methods: In the Autoimmunity Screening for Kids study, 91 children persistently islet autoantibody positive (median age 11.5 y, 48% non-Hispanic White, 57% female) with a baseline CGM were followed for development of diabetes for a median of 6 (range:0.2-34) months. Of these, 16 (18%) progressed to clinical diabetes in a median of 4.5 (range:0.4-29 months. </p> <p>Results: Compared to non-progressors, progressors had significantly higher average sensor glucose (119 vs 105 mg/dL) and increased glycemic variability: SD 27 vs 16, CV 21 vs 15, MODD 24 vs 16 and MAGE 43 vs 26. Progressors spent 21% of <a>time above 140 mg/dl </a>(TA140) and 8% above 160 mg/dl, compared to 3% and 1%, respectively, for non-progressors. <a>In survival analyses, the risk of progression to diabetes in one year was 80% in those with TA140 >10%; in contrast, it was only 5% in the other participants. </a><a>Performance of prediction by receiver operating curve analyses showed area under the curve of <u>></u>0.89 for both individual and combined CGM metric models</a>. </p> <p>Conclusions<a>: </a><a>TA140 >10% is associated with a high risk of progression to clinical diabetes within the next year</a> in autoantibody positive children. CGM should be included in the ongoing monitoring of high-risk children<a></a><a> a</a>nd could be used as potential entry criteria for prevention trials. </p>

Hemoglobin A1c and Fructosamine Evaluated in Patients with Type 2 Diabetes Receiving Peritoneal Dialysis Using Long-Term Continuous Glucose Monitoring

<b><i>Introduction:</i></b> Shortened erythrocyte life span and erythropoietin-stimulating agents may affect hemoglobin A_1c (HbA_1c) levels in patients receiving peritoneal dialysis (PD). We compared HbA_1c with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with type 2 diabetes receiving PD. <b><i>Methods:</i></b> Fourteen days of CGM (Ipro2, Medtronic) were performed in 23 patients with type 2 diabetes receiving PD and in 23 controls with type 2 diabetes and an estimated glomerular filtration rate over 60 mL/min/1.73 m². Patients were matched on gender and age (±5 years). HbA_1c (mmol/mol), its derived estimate of mean plasma glucose (eMPG_A1c) (mmol/L), and fructosamine (µmol/L) were measured at the end of the CGM period and compared with the mean sensor glucose (mmol/L) from CGM. <b><i>Results:</i></b> In the PD group, mean sensor glucose was 0.98 (95% con­fidence interval (CI): 0.43–1.54) mmol/L higher than the eMPG_A1c compared with the control group (<i>p</i> = 0.002) where glucose levels were nearly identical (−0.05 (95% CI: −0.35–0.25) mmol/L). A significant association was found between fructosamine and mean sensor glucose using linear regression with no difference between slopes (<i>p</i> = 0.89) or y-intercepts (<i>p</i> = 0.28). <b><i>Discussion/Conclusion:</i></b> HbA_1c underestimates mean plasma glucose levels in patients with type 2 diabetes receiving PD. However, the clinical significance of this finding is undetermined. Fructosamine seems to more accurately reflect glycemic status. CGM or fructosamine could complement HbA_1c to increase the accuracy of glycemic monitoring in the PD population.

Continuous glucose monitoring in extremely preterm infants in intensive care: the REACT RCT and pilot study of ‘closed-loop’ technology

Background Hyperglycaemia and hypoglycaemia are common in preterm infants and are associated with increased mortality and morbidity. Continuous glucose monitoring is widely used to target glucose control in adults and children, but not in neonates. Objective To evaluate the role of continuous glucose monitoring in the preterm infant. Design The REAl-time Continuous glucose moniToring in neonatal intensive care project combined (1) a feasibility study, (2) a multicentre randomised controlled trial and (3) a pilot of ‘closed-loop’ continuous glucose monitoring. The feasibility study comprised a single-centre study (n = 20). Eligibility criteria included a birthweight ≤ 1200 g and aged ≤ 48 hours. Continuous glucose monitoring was initiated to support glucose control. The efficacy and safety outcomes guided the design of the randomised controlled trial. The randomised controlled trial comprised a European multicentre trial (n = 182). Eligibility criteria included birthweight ≤ 1200 g and aged ≤ 24 hours. Exclusion criteria included any lethal congenital abnormality. Continuous glucose monitoring was initiated to support glucose control within 24 hours of birth. In the intervention group, the continuous glucose monitoring sensor provided real-time data on glucose levels, which guided clinical management. In control infants, the continuous glucose monitoring data were masked, and glucose level was managed in accordance with standard clinical practice and based on the blood glucose levels. The primary outcome measure was the percentage of time during which the sensor glucose level was within the target range of 2.6–10 mmol/l. Secondary outcome measures included mean sensor glucose level, the percentage of time during which the sensor glucose level was within the target range of 4–8 mmol/l, the percentage of time during which the sensor glucose level was in the hyperglycaemic range (i.e. > 15 mmol/l) and sensor glucose level variability. Safety outcomes included hypoglycaemia exposure. Acceptability assessment and health economic analyses were carried out and further exploratory health outcomes were explored. The mean percentage of time in glucose target range of 2.6–10 mmol/l was 9% higher in infants in the continuous glucose monitoring group (95% confidence interval 3% to 14%; p = 0.002), and the mean time in the target range of 4–8 mmol/l was 12% higher in this group (95% confidence interval 4% to 19%; p = 0.004). There was no difference in the number of episodes of hypoglycaemia. Exploratory outcomes showed a reduced risk of necrotising enterocolitis in the intervention arm (odds ratio 0.33, 95% confidence interval 0.13 to 0.78; p = 0.01). Health economic analyses demonstrated that continuous glucose monitoring was cost-effective on the basis of the cost per additional case of adequate glucose control between 2.6 and 10 mmol/l. The ‘closed-loop’ study was a single-center pilot study, with eligibility criteria including a birthweight of ≤ 1200 g and aged ≤ 48 hours. Infants underwent continuous glucose monitoring for the first week of life (n = 21), with those in the intervention group receiving closed-loop insulin delivery between 48 and 72 hours of age. The primary outcome of percentage of time in the target range (i.e. sensor glucose 4–8 mmol/l) increased from a median of 26% (interquartile range 6–64%) to 91% (interquartile range 78–99%) during closed-loop insulin delivery (p < 0.001). Limitations These studies have not defined the optimal targets for glucose control or the best strategies to achieve them in these infants. Future work Studies are needed to evaluate the longer-term impact of targeting glucose control on clinical outcomes. Conclusions Continuous glucose monitoring in extremely preterm infants can improve glucose control, with closed-loop insulin delivery having further potential to target glucose levels. Staff and parents felt that the use of continuous glucose monitoring improved care and the results of the health economic evaluation favours the use of continuous glucose monitoring. Trial registration Current Controlled Trials ISRCTN12793535. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 16. See the NIHR Journals Library website for further project information. Medtronic plc provided some MiniMed™ 640G systems and Nova Biomedical (Waltham, MA, USA) provided point-of-care devices.

The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis

<b><i>Introduction:</i></b> The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD. <b><i>Methods:</i></b> Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate &#x3e;60 mL/min/1.73 m²) completed the study period of 17 weeks. CGM (Ipro2^®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (μmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM. <b><i>Findings:</i></b> In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0–1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: −0.1–[0.4]; <i>p</i> &#x3c; 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (−7.3 mmol/mol, 95% CI: −10.0–[−4.7]) than in the control group (<i>p</i> &#x3c; 0.001), with no difference detected for fructosamine (<i>p</i> = 0.64). <b><i>Discussion:</i></b> HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.

The utility of continuous glucose monitoring systems in the management of children with persistent hypoglycaemia

Objectives Glucose monitoring is vital in children with persistent hypoglycaemia to reduce the risk of adverse neuro-behavioural outcomes; especially in children with hyperinsulinism. The role of continuous glucose monitoring (CGM) systems in monitoring glucose levels in this cohort is limited. The objective of this study was to ascertain the effectiveness of CGM and to evaluate parents’ experience of using CGM for monitoring glucose levels in children with hypoglycaemia. Methods Retrospective analysis of sensor glucose (SG) values from Dexcom G4 CGM with paired finger-prick blood glucose (BG) values was performed to determine the accuracy of CGM. The parent experience of CGM was assessed using a questionnaire administered to families of children with congenital hyperinsulinism currently attending the clinic. Results SG data from 40 children (median age 6 months) with persistent hypoglycaemia (60% Hyperinsulinism) were analysed. The mean difference between 5,650 paired BG and SG values was 0.28 mmol/L. The sensitivity and specificity of CGM to identify severe hypoglycaemia (BG < 3.0 mmol/L) were 54.3% (95% CI: 39.0%, 69.1%) and 97.4% (95% CI: 96.9%, 97.8%) respectively. Parents (n=11) reported less anxiety (n=9), better sleep at night (n=7) and preferred to use CGM for monitoring (n=9). Conclusions Although the high number of false-positive readings precludes the routine use of CGM in the evaluation of hypoglycaemia, it avoids unnecessary BG testing during normoglycaemia. It is an acceptable tool for parents for monitoring their children who are at risk of hypoglycaemia. Newer CGM systems with improved accuracy at lower glucose levels have the potential to further improve monitoring.

Continuous Glucose Monitoring in the Management of Neonates with Persistent Hypoglycaemia and Congenital Hyperinsulinism

Background Persistent hypoglycaemia is common in the newborn and is associated with poor neurodevelopmental outcome. Adequate monitoring is critical in prevention, but is dependent on frequent, often hourly blood sampling. Continuous glucose monitoring (CGM) is increasingly being used in children with type 1 diabetes mellitus, but use in neonatology remains limited. We aimed to introduce real-time CGM to provide insights into patterns of dysglycaemia and to support the management of persistent neonatal hypoglycaemia. Methods This is a single centre retrospective study of real-time CGM use over a 4-year period in babies with persistent hypoglycaemia. Results CGMs were inserted in 14 babies: 8 term and 6 preterm infants, 9 with evidence of congenital hyperinsulinism (CHI). A total of 224 days of data were collected demonstrating marked fluctuations in glucose levels in babies with CHI, with a higher sensor glucose SD (1.52±0.79 mmol/l vs 0.77±0.22mmol/l) in infants with CHI compared to preterm infants. A total of 1254 paired glucose values (CGM and blood) were compared and gave a mean absolute relative difference (MARD) of 11%. Conclusion CGM highlighted the challenges of preventing hypoglycaemia in these babies when using intermittent blood glucose levels alone, and the potential application of CGM as an adjunct to clinical care.

Accuracy of CGM Systems During Continuous and Interval Exercise in Adults with Type 1 Diabetes

Background: continuous glucose monitoring systems (CGMs) play an important role in the management of T1D, but their accuracy may reduce during rapid glucose excursions. The aim of study was to assess the accuracy of recent rt-CGMs available in Italy, in subjects with T1D during 2 sessions of physical activity: moderate continuous (CON) and interval exercise (IE). Method: we recruited 22 patients with T1D, on CSII associated or integrated with a CGM, to which a second different sensor was applied. Data recorded by CGMs were compared with the corresponding plasma glucose (PG) values, measured every 5 minutes with the glucose analyzer. To assess the accuracy of the CGMs, we evaluated the Sensor Bias (SB), the Mean Absolute Relative Difference (MARD) and the Clarke error grid (CEG). Results: a total of 2355 plasma-sensor glucose paired points were collected. Both average plasma and interstitial glucose concentrations did not significantly differ during CON and IE. During CON: 1. PG change at the end of exercise was greater than during IE ( P = .034); 2. all sensors overestimated PG more than during IE, as shown by SB ( P < .001) and MARD ( P < .001) comparisons. Classifying the performance according to the CEG, significant differences were found between the 2 sessions in distribution of points in A and B zones. Conclusions: the exercise affects the accuracy of currently available CGMs, especially during CON, suggesting, in this circumstance, the need to maintain blood glucose in a “prudent” range, above that generally recommended. Further studies are needed to investigate additional types of activities.

Hemodialysis-Related Glycemic Disarray Proven by Continuous Glucose Monitoring: Glycemic Markers and Hypoglycemia

<b>OBJECTIVE</b> <p>There is a high risk of asymptomatic hypoglycemia associated with hemodialysis (HD) using glucose-free dialysate; therefore, the inclusion of glucose in the dialysate is believed to prevent intradialytic hypoglycemia. However, the exact glycemic fluctuation profiles and frequency of asymptomatic hypoglycemia using dialysates containing >100 mg/dL glucose have not been determined.</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>We evaluated the glycemic profiles of 98 type 2 diabetes patients undergoing HD (68 men, HbA1c 6.4±1.2%, glycated albumin 20.8±6.8%) with a dialysate containing 100, 125, or 150 mg/dL glucose using continuous glucose monitoring.</p> <p><b>RESULTS</b></p> <p>Sensor glucose level (SGL) showed a sustained decrease during HD, irrespective of the dialysate glucose concentration, and reached a nadir that was lower than the dialysate glucose concentration in 49 participants (50%). Twenty-one participants (21%) presented with HD-related hypoglycemia, defined by an SGL <70 mg/dL during HD and/or between the end of HD and their next meal. All these hypoglycemic episodes were asymptomatic. Measures of glycemic variability calculated using the SGL data (standard deviation, coefficient of variation, and range of SGL) were higher and time below range (<70 mg/dL) was lower in participants who experienced HD-related hypoglycemia than in those who did not, whereas time in range between 70 and 180 mg/dL, time above range (>180 mg/dL), HbA1c and GA of the two groups were similar.</p> <p><b>CONCLUSIONS</b></p> <p>Despite the use of dialysate containing 100–150 mg/dL glucose, diabetic HD patients experienced HD-related hypoglycemia unawareness frequently. SGL may fall well below the dialysate glucose concentration toward the end of HD.<br> </p>