Real-world glycaemic outcomes in patients with type 1 diabetes using glucose sensors-Experience from a single centre in Dublin.

AIMS: To evaluate changes in glycated haemoglobin (HbA1 c) and sensor-based glycaemic metrics after glucose sensor commencement in adults with T1D. METHODS: We performed a retrospective observational single-centre study on HbA1 c, and sensor-based glycaemic data following the initiation of continuous glucose monitoring (CGM) in adults with T1D (n = 209). RESULTS: We observed an overall improvement in HbA1 c from 66 (59-78) mmol/mol [8.2 (7.5-9.3)%] pre-sensor to 60 (53-71) mmol/mol [7.6 (7.0-8.6)%] on-sensor (p < .001). The pre-sensor HbA1 c improved from 66 (57-74) mmol/mol [8.2 (7.4-8.9)%] to 62 (54-71) mmol/mol [7.8 (7.1-8.7)%] within the first year of usage to 60 (53-69) mmol/mol [7.6 (7.0-8.4)%] in the following year (n = 121, p < .001). RT-CGM-user had a significant improvement in HbA1 c (Dexcom G6; p < .001, r = 0.33 and Guardian 3; p < .001, r = 0.59) while a non-significant reduction was seen in FGM-user (Libre 1; p = .279). Both MDI (p < .001, r = 0.33) and CSII group (p < .001, r = 0.41) also demonstrated significant HbA1 c improvement. Patients with pre-sensor HbA1 c of ≥64 mmol/mol [8.0%] (n = 125), had attenuation of pre-sensor HbA1 c from 75 (68-83) mmol/mol [9.0 (8.4-9.7)%] to 67 (59-75) mmol/mol [8.2 (7.6-9.0)%] (p < .001, r = 0.44). Altogether, 25.8% of patients achieved the recommended HbA1 c goal of ≤53 mmol/mol and 16.7% attained the recommended ≥70% time in range (3.9-10.0 mmol/L). CONCLUSIONS: Our study demonstrated that minimally invasive glucose sensor technology in adults with T1D is associated with improvement in glycaemic outcomes. However, despite significant improvements in HbA1 c, achieving the recommended goals for all glycaemic metrics remained challenging.

Examining a Remote Group-Based Type 2 Diabetes Self-Management Education Program in the COVID-19 Era Using the ORBIT Model: Small 6-Week Feasibility Study.

BACKGROUND: To date, most group-based diabetes self-management education (DSME) programs for type 2 diabetes (T2D) have been delivered in person. The rapid transition to remote care at the outset of the COVID-19 pandemic presented opportunities to test, evaluate, and iterate a new remote DSME program. OBJECTIVE: We aim to refine the delivery and evaluation of a multicomponent remote DSME program for adults living with T2D by examining several feasibility outcomes. METHODS: We recruited a convenience sample of patients from a London, Canada, outpatient diabetes clinic (serving high-risk, low-income adults) to participate in a 6-week, single cohort feasibility study from November 2020 to March 2021. This small ORBIT phase 1b feasibility study represents the first in a planned series guided by the ORBIT model for developing behavioral interventions for chronic diseases (phase 1: design; phase 2: preliminary testing; phase 3: efficacy; and phase 4: effectiveness). The feasibility of delivering and evaluating a remote DSME program, including (1) live video education classes, (2) individualized physical activity (PA) prescription and counseling, and (3) intermittently scanned continuous glucose and wearable PA monitoring, was assessed. Feasibility outcomes included recruitment and retention rates, program adherence, and acceptability (ie, technology issues and exit survey feedback). PA was assessed with Fitbit Inspire 2 (Fitbit Inc) and estimated glycated hemoglobin (HbA1c) using the FreeStyle Libre (Abbot). Given the small study sample, group- and individual-level data are reported descriptively. RESULTS: A total of 10 adults living with T2D were recruited (female 60%; age 49.9, SD 14.3 years; estimated HbA1c 6.2%, SD 0.5%). Recruitment and retention rates were 29% and 80%, respectively. Participants attended 83% (25/30) and 93% (37/40) of education classes and PA counseling phone calls, respectively. There were 3.2 (SD 2.6) technology issues reported per person, most of which were related to study data transfer. Exit survey responses suggest most participants (8/9, 89%) were "satisfied" with the program. Recognizing the small sample size and the fact that no inferential statistics were conducted, the mean (SD) for the weekly daily step count and estimated HbA1c are provided for illustrative purposes. Participants accumulated 7103 (SD 2900) and 7515 (SD 3169) steps per day at baseline and week 6, respectively. The estimated HbA1c was 6.2% (SD 0.5%) and 6.2% (SD 0.6%) at baseline and week 6, respectively. CONCLUSIONS: This ORBIT phase 1b study served to refine the delivery (eg, automatic study data upload process recommended to reduce participant burden) and evaluation (eg, purposeful sampling of participants with baseline HbA1c >8% recommended to address selection bias) of a remote DSME program. Preliminary proof-of-concept testing (ORBIT phase 2) incorporating some of these learnings is now warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT04498819; https://clinicaltrials.gov/study/NCT04498819.

Assessment of the FreeStyle Libre 2 interstitial glucose monitor in hypo- and euglycemic cats.

BACKGROUND: Continuous glucose monitoring systems have been validated for eu- and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). OBJECTIVES: Assess FSL2 accuracy in cats with hypoglycemia. ANIMALS: Nine healthy, purpose-bred cats. METHODS: Hyperinsulinemic-hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland-Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P < .05 considered significant). RESULTS: Overall, BG and IG correlated strongly (r = 0.83, P < .0001) in stable glycemia and moderately at all rates of change (r = 0.69, P < .0001). Interstitial glucose concentration underestimated BG in euglycemia, but the BG-IG difference was progressively smaller as BG decreased (12.9 ± 12.2, 8.8 ± 11.2, -3.2 ± 7.4, and -7.8 ± 5.2 mg/dL in the ranges of 80-120 [n = 64], 60-79 [n = 29], 50-59 [n = 71], and 29-49 mg/dL [n = 53], respectively). CONCLUSIONS: Although IG underestimates BG throughout most of the hypo-euglycemic range, IG generally overestimates BG in marked hypoglycemia (<60 mg/dL). It is therefore imperative to evaluate FSL2 results in this critical range with caution.

Performance of the FreeStyle Libre Flash Glucose Monitoring System during an Oral Glucose Tolerance Test and Exercise in Healthy Adolescents.

This study's aim was to assess FreeStyle Libre Flash glucose monitoring (FGM) performance during an oral glucose tolerance test (OGTT) and treadmill exercise in healthy adolescents. This should advance the feasibility and utility of user-friendly technologies for metabolic assessments in adolescents. Seventeen healthy adolescents (nine girls aged 12.8 ± 0.9 years) performed an OGTT and submaximal and maximal treadmill exercise tests in a laboratory setting. The scanned interstitial fluid glucose concentration ([ISFG]) obtained by FGM was compared against finger-prick capillary plasma glucose concentration ([CPG]) at 0 (pre-OGTT), -15, -30, -60, -120 min post-OGTT, pre-, mid-, post- submaximal exercise, and pre- and post- maximal exercise. Overall mean absolute relative difference (MARD) was 13.1 ± 8.5%, and 68% (n = 113) of the paired glucose data met the ISO 15197:2013 criteria. For clinical accuracy, 84% and 16% of FGM readings were within zones A and B in the Consensus Error Grid (CEG), respectively, which met the ISO 15197:2013 criteria of having at least 99% of results within these zones. Scanned [ISFG] were statistically lower than [CPG] at 15 (-1.16 mmol∙L-1, p < 0.001) and 30 min (-0.74 mmol∙L-1, p = 0.041) post-OGTT. Yet, post-OGTT glycaemic responses assessed by total and incremental areas under the curve (AUCs) were not significantly different, with trivial to small effect sizes (p ≥ 0.084, d = 0.14-0.45). Further, [ISFGs] were not different from [CPGs] during submaximal and maximal exercise tests (interaction p ≥ 0.614). FGM can be a feasible alternative to reflect postprandial glycaemia (AUCs) in healthy adolescents who may not endure repeated finger pricks.

The Benefits of Utilizing Continuous Glucose Monitoring of Diabetes Mellitus in Primary Care: A Systematic Review.

BACKGROUND: Continuous glucose monitoring (CGM) and intermittently scanned CGM (is-CGM) have shown to effectively manage diabetes in the specialty setting, but their efficacy in the primary care setting remains unknown. Does CGM/is-CGM improve glycemic control, decrease rates of hypoglycemia, and improve staff/physician satisfaction in primary care? If so, what subgroups of patients with diabetes are most likely to benefit? METHODS: A comprehensive search in seven databases was performed in June 2021 for primary studies examining any continuous glucose monitoring system in primary care. We excluded studies with fewer than 20 participants, specialty care only, or hospitalized participants. The National Heart, Lung and Blood Institute and Grading of Recommendations Assessment, Development and Evaluation were used for the quality assessment. The weighted mean difference (WMD) of HbA1c between CGM/is-CGM and usual care with 95% confidence interval was calculated. A narrative synthesis was conducted for change of time in, above, or below range (TIR, TAR, and TBR) hypoglycemic events and staff/patient satisfaction. RESULTS: From ten studies and 4006 participants reviewed, CGM was more effective at reducing HbA1c compared with usual care (WMD -0.43%). There is low certainty of evidence that CGM/is-CGM improves TIR, TAR, or TBR over usual care. The CGM can reduce hypoglycemic events and staff/patient satisfaction is high. Patients with intensive insulin therapy may benefit more from CGM/is-CGM. CONCLUSIONS: Compared with usual care, CGM/is-CGM can reduce HbA1c, but most studies had notable biases, were short duration, unmasked, and were sponsored by industry. Further research needs to confirm the long-term benefits of CGM/is-CGM in primary care.

Validity of Danish public criteria for providing flash glucose monitoring to participants with type 1 diabetes-An explorative cohort study.

INTRODUCTION: Flash glucose monitor (FGM) use is increasing. A set of Danish criteria for regulating the use has been released. We assessed their validity. METHODS: Patients with type 1 diabetes attending our clinic were offered Freestyle Libre Sensor for 12 months and stratified into fulfilling the Danish regional criteria (RC+) or not (RC-). Primary endpoint was achieving individualized target HbA1c. Secondary endpoints were HbA1c reduction ≥5%, time in range (TIR), time below range (TBR), daily scans, change in median HbA1c, and noted experiences. RESULTS: Two hundred seventy-eight participants were included. Forty-four participants met target HbA1c after 1 year. No difference between RC+ and RC- was observed (p = .136). Higher age was associated with probability to meet target HbA1c (RR = 3.15, [95% CI: 1.15, 8.62]) as was frequent scans (RR = 1.88, [95% CI: 0.99, 3.57]). One hundred twenty-three participants met an HbA1c reduction ≥5%, the majority represented in RC+ (p = .023). Higher baseline HbA1c was associated with a reduction of HbA1c ≥5% after 1 year (RR = 1.97, [95% CI: 1.40, 2.78]). There was no difference between RC+ and RC- in TIR, TBR, and daily scans. Positive experiences dominated from both participants and healthcare professionals. More positive experiences were noted from healthcare professionals in RC- (p = .003) but no difference in reported experiences among participants in RC+ and RC- (p = .880). CONCLUSION: The Danish Regional Criteria seems not a valid tool for regulation of FGM. Participants of older age and participants with more frequent daily scans might benefit more from FGM.

Association between Flash Glucose Monitors and A1C: A Retrospective Pre-Post Analysis.

Background: Randomized controlled trials have investigated the effect of continuous glucose monitors on hemoglobin A1C; however, more evidence is needed to justify their use and expand insurance coverage. Additionally, there are few published studies investigating the A1C lowering effect of flash glucose monitors (FGMs) in broad diabetes populations with varying insulin requirements. This analysis aimed to help fill this gap in medical literature and help clinicians evaluate costs/benefits when considering FGMs for their patients with diabetes. Objectives: To determine the association between FGM use and A1C reduction in patients with type 1 or type 2 diabetes mellitus regardless of insulin dependence. Methods: Pharmacy dispensing records were used to identify patients for inclusion. Patients who received a FGM from a University of Utah pharmacy between July 7, 2018 and July 7, 2020 were included. Patients who did not receive at least an 84-day supply of FGM sensors or did not have a baseline or follow-up A1C were excluded. Baseline and follow-up A1Cs, defined as A1Cs that are within one year before and 3-12 months after the FGM dispense date, were collected for each patient. New diabetes medications within a six-month window of the initial FGM dispense date were also recorded. Outcome variables were collected before and after patients received their first FGM (pre-FGM vs. post-FGM, respectively). The primary outcome was the difference between baseline and follow-up A1C for each patient. Secondary outcomes were the difference in baseline and follow-up A1C for various clinical subgroups within the overall sample. Descriptive statistics were used to summarize baseline characteristics and outcome data. Paired Student's t-tests were used to evaluate outcome differences (α=0.05). Results: Fifty-seven patients (50.8% male; mean age: 49 years) were included. For the primary outcome, the average baseline and follow-up A1Cs were 9.33% and 8.32%, respectively for a difference of -1.01% ([95%CI -1.31:-0.72]; p<0.0001). Conclusions: The use of FGMs is associated with decreases in A1C within a cohort of patients at one health system. Further effort to determine impact of FGM on clinical and economic outcomes is warranted.

Determinants of HbA1c reduction with FreeStyle Libre flash glucose monitoring (FLARE-NL 5).

AIMS: To identify factors predicting HbA1c reduction in patients with diabetes mellitus (DM) using FreeStyle Libre Flash Glucose Monitoring (FSL-FGM). METHODS: Data from a 12-month prospective nation-wide FSL registry were used and analysed with multivariable regression. For the present study we included patients with hypoglycaemia unawareness or unexpected hypoglycaemias (n = 566) and persons who did not reach acceptable glycaemic control (HbA1c > 70 mmol/mol (8.5%)) (n = 294). People with other indications for use, such as sensation loss of the fingers or individuals already using FSL-FGM or rtCGM, were excluded (37%). RESULTS: Eight hundred and sixty persons (55% male with a mean age of 46.7 (±16.4) years) were included. Baseline HbA1c was 65.1 (±14.5) mmol/mol (8.1 ± 1.3%), 75% of the patients had type 1 DM and 37% had microvascular complications. Data concerning HbA1c was present for 482 (56.0%) at 6 months and 423 (49.2%) persons at 12 months. A significant reduction in HbA1c (≥5 mmol/mol (0.5%)) was present in 187 (22%) persons. For these persons, median HbA1c reduction was -9.0 [-13.0, -4.0] mmol/mol (-0.82 [-1.19, -0.37]%) at 6 months and -9.0 [-15.0, -7.0] mmol/mol (-0.82 [-1.37, -0.64]%) at 12 months. In multivariable regression analysis with age, gender and SF-12 physical and mental component scores as covariates, only baseline HbA1c was significant: -0.319 (SE 0.025; p < 0.001; R2 = 0.240 for the model). In exploratory analysis among subgroups with different indications for FSL-FGM use (hypoglycaemia unawareness or persistently high HbA1c) and persons with a significant HbA1c decrease over the study period, baseline HbA1c remained the only significant predictor. CONCLUSIONS: Among the variables we analysed in the present study, only high HbA1c at baseline predicts significant HbA1c reduction during FSL-CGM use.

Flash glucose monitoring system was applied to cortisol treatment for a patient with congenital adrenal hyperplasia and 17α-hydroxylase deficiency.

BACKGROUND: Congenital adrenal hyperplasia (CAH) with 17α-hydroxylase deficiency is a rare disease; patients often require lifetime cortisol treatment. In this case report, we presented a patient with CAH and 17α-hydroxylase deficiency, who was previously misdiagnosed as having primary aldosteronism. Furthermore, the flash glucose monitoring system (FGMS) was used to ascertain a suitable cortisol therapeutic regimen for this patient. CASE PRESENTATION: A 29-year-old woman presented with sex dysgenesis, hypertension and hypokalaemia. She had been diagnosed with primary aldosteronism at a local hospital. The re-measured aldosterone level in our hospital was below the normal range after antihypertensive medication adjustment, suggesting that the primary aldosteronism was a misdiagnosis. The patient was finally diagnosed as having CAH with 17α-hydroxylase deficiency according to the endocrine profile, adrenocorticotropic hormone stimulation test, and genetic analysis. Then, the patient was recommended cortisol treatment, during which the endocrine profile, blood pressure, plasma potassium level, and blood glucose level were observed to ascertain a suitable dosage. The FGMS was used to monitor blood glucose level, which indicated that the patient's glucose metabolism was maintained normally under the final treatment dosage. CONCLUSION: The misdiagnosis might have been because of the effects of the antihypertension medications on aldosterone and renin levels. The final dosage of cortisol treatment achieved a normal endocrine profile, while maintaining the homeostasis of blood glucose level, plasma potassium level and blood pressure. FGMS may be an effective method to ascertain a suitable cortisol therapeutic regimen for patients with CAH and 17α-hydroxylase deficiency.

Safety and Accuracy of Factory-Calibrated Continuous Glucose Monitoring in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation.

Background: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) may be at risk for malglycemia and adverse outcomes, including infection, prolonged hospital stays, organ dysfunction, graft-versus-host-disease, delayed hematopoietic recovery, and increased mortality. Continuous glucose monitoring (CGM) may aid in describing and treating malglycemia in this population. However, no studies have demonstrated safety, tolerability, or accuracy of CGM in this uniquely immunocompromised population. Materials and Methods: A prospective observational study was conducted, using the Abbott Freestyle Libre Pro, in patients aged 2-30 undergoing HSCT at Children's Hospital Colorado to evaluate continuous glycemia in this population. CGM occurred up to 7 days before and 60 days after HSCT, during hospitalization only. In a secondary analysis of this data, blood glucoses collected during routine HSCT care were compared with CGM values to evaluate accuracy. Adverse events and patient refusal to wear CGM device were monitored to assess safety and tolerability. Results: Participants (n = 29; median age 13.1 years, [interquartile range] [4.7, 16.6] years) wore 84 sensors for an average of 25 [21.5, 30.0] days per participant. Paired serum-sensor values (n = 893) demonstrated a mean absolute relative difference of 20% ± 14% with Clarke Error Grid analysis showing 99% of pairs in the clinically acceptable Zones (A+B). There were four episodes of self-limited bleeding (4.8% of sensors); no other adverse events occurred. Six patients (20.7%) refused subsequent CGM placements. Conclusions: CGM use appears safe and feasible although with suboptimal accuracy in the hospitalized pediatric HSCT population. Few adverse events occurred, all of which were low grade.

Differences Between Flash Glucose Monitor and Fingerprick Measurements.

Freestyle Libre (FL) is a factory calibrated Flash Glucose Monitor (FGM). We investigated Mean Absolute Relative Difference (MARD) between Self Monitoring of Blood Glucose (SMBG) and FL measurements in the first day of sensor wear in 39 subjects with Type 1 diabetes. The overall MARD was 12.3%, while the individual MARDs ranged from 4% to 25%. Five participants had a MARD ≥ 20%. We estimated bias and lag between the FL and SMBG measurements. The estimated biases range from -1.8 mmol / L to 1.4 mmol / L , and lags range from 2 min to 24 min . Bias is identified as a main cause of poor individual MARDs. The biases seem to persist in days 2⁻7 of sensor usage. All cases of MARD ≥ 20% in the first day are eliminated by bias correction, and overall MARD is reduced from 12.3% to 9.2%, indicating that adding support for voluntary user-supplied bias correction in the FL could improve its performance.

A Clinical Trial of the Accuracy and Treatment Experience of the Flash Glucose Monitor FreeStyle Libre in Adults with Type 1 Diabetes.

BACKGROUND: In Sweden, FreeStyle Libre a flash glucose monitoring system came onto the market in 2014 as a complement to self-monitoring of blood glucose. The aim of this study was to evaluate the accuracy and treatment experience of the FreeStyle Libre system. METHODS: Fifty-eight adults with type 1 diabetes used FreeStyle Libre for 10-14 days and measured capillary blood glucose levels with the HemoCue blood glucose measurement system at least six times a day simultaneously. RESULTS: For the entire study period, the mean absolute relative difference (MARD) was 13.2% (95% confidence interval [CI] 12.0%-14.4%). MARD was 13.6% (95% CI 12.1%-15.4%) during week 1 and 12.7% (95% CI 11.5%-13.9%) during week 2. The mean absolute difference (MAD) for the whole study period was 19.8 mg/dL (1.1 mmol/L) (95% CI 17.8-21.8 mg/dL), including 20.5 mg/dL (1.14 mmol/L) during week 1 and 19.0 mg/dL (1.05 mmol/L) during week 2. The overall correlation coefficient was 0.96. For glucose values <72, 72-180, and >180 mg/dL (<4, 4-10, and >10 mmol/L), the MARD was 20.3% (95% CI 17.7%-23.1%), 14.7% (95% CI 13.4%-16%), and 9.6% (95% CI 8.5%-10.8%), respectively, and respective MAD values were 12.3, 17.8, and 23.6 mg/dL (0.69, 0.99, and 1.31 mmol/L). Using the 10-item visual analog scale, patients rated their experience with FreeStyle Libre as generally positive, with mean values ranging from 8.22 to 9.8. CONCLUSIONS: FreeStyle Libre had a similar overall MARD as continuous blood glucose monitoring systems in earlier studies when studied in similar at-home conditions. The overall patient satisfaction was high.