Comparing real-time and intermittently scanned continuous glucose monitoring in adults with type 1 diabetes (ALERTT1): a 6-month, prospective, multicentre, randomised controlled trial.

BACKGROUND: People with type 1 diabetes can continuously monitor their glucose levels on demand (intermittently scanned continuous glucose monitoring [isCGM]), or in real time (real-time continuous glucose monitoring [rtCGM]). However, it is unclear whether switching from isCGM to rtCGM with alert functionality offers additional benefits. Therefore, we did a trial comparing rtCGM and isCGM in adults with type 1 diabetes (ALERTT1). METHODS: We did a prospective, double-arm, parallel-group, multicentre, randomised controlled trial in six hospitals in Belgium. Adults with type 1 diabetes who previously used isCGM were randomly assigned (1:1) to rtCGM (intervention) or isCGM (control). Randomisation was done centrally using minimisation dependent on study centre, age, gender, glycated haemoglobin (HbA1c), time in range (sensor glucose 3·9-10·0 mmol/L), insulin administration method, and hypoglycaemia awareness. Participants, investigators, and study teams were not masked to group allocation. Primary endpoint was mean between-group difference in time in range after 6 months assessed in the intention-to-treat sample. This trial is registered with ClinicalTrials.gov, NCT03772600. FINDINGS: Between Jan 29 and Jul 30, 2019, 269 participants were recruited, of whom 254 were randomly assigned to rtCGM (n=127) or isCGM (n=127); 124 and 122 participants completed the study, respectively. After 6 months, time in range was higher with rtCGM than with isCGM (59·6% vs 51·9%; mean difference 6·85 percentage points [95% CI 4·36-9·34]; p<0·0001). After 6 months HbA1c was lower (7·1% vs 7·4%; p<0·0001), as was time <3·0 mmol/L (0·47% vs 0·84%; p=0·0070), and Hypoglycaemia Fear Survey version II worry subscale score (15·4 vs 18·0; p=0·0071). Fewer participants on rtCGM experienced severe hypoglycaemia (n=3 vs n=13; p=0·0082). Skin reaction was more frequently observed with isCGM and bleeding after sensor insertion was more frequently reported by rtCGM users. INTERPRETATION: In an unselected adult type 1 diabetes population, switching from isCGM to rtCGM significantly improved time in range after 6 months of treatment, implying that clinicians should consider rtCGM instead of isCGM to improve the health and quality of life of people with type 1 diabetes. FUNDING: Dexcom.

Sustained Impact of Intermittently Scanned Continuous Glucose Monitoring on Treatment Satisfaction and Severe Hypoglycemia in Adults with Type 1 Diabetes (FUTURE): An Analysis in People with Normal and Impaired Awareness of Hypoglycemia.

Objective: Nationwide reimbursement of intermittently scanned continuous glucose monitoring (isCGM) was introduced in Belgium (2016). This real-world observational study investigates the impact of isCGM over 24 months on adults with type 1 diabetes with impaired or normal awareness of hypoglycemia (IAH or NAH). Methods: We included 1905 people who started first-generation 14-day FreeStyle Libre (without alerts). Sixteen percent had IAH. Primary endpoint was evolution of quality of life (QOL); secondary endpoints were evolution of severe hypoglycemia, work absenteeism, glycated hemoglobin (HbA1c), and sensor-measured outcomes. Results: At baseline, people with IAH (n = 308) had significantly worse QOL than people with NAH (n = 1594). Only people with IAH improved on the hypoglycemia fear survey-worry subscale after 24 months (22.8 [95% confidence interval: 21.4-24.2] at baseline; 20.6 [19.0-22.1] at 24 months, P = 0.002). For both groups, Diabetes Treatment Satisfaction Scale improved over 24 months (IAH: +3.1 [2.1-4.1], P < 0.001; NAH: +2.3 [1.9-2.7], P < 0.001), whereas general QOL, diabetes distress, and HbA1c remained stable. People with IAH showed the strongest decline in work absenteeism and severe hypoglycemia (36.4% having an event 6 months before isCGM initiation; 16.0% having an event during last 6 months of follow-up, P < 0.001), with similar observations for hypoglycemia hospitalization and hypoglycemia coma. Over 24 months, people with IAH spent more time in hypoglycemia, but less time in hyperglycemia than people with NAH. Conclusion: These data show sustained improvement of severe hypoglycemia, work absenteeism, and hypoglycemia fear after isCGM reimbursement, mostly driven by people with IAH. Together with improved treatment satisfaction, irrespective of hypoglycemia awareness level, isCGM without alerts is a valuable tool under long-term real-world conditions. Clinical Trial Registration number: NCT02898714.

Effect of switching from intermittently scanned to real-time continuous glucose monitoring in adults with type 1 diabetes: 24-month results from the randomised ALERTT1 trial.

BACKGROUND: Comparing Continuous With Flash Glucose Monitoring In Adults With Type 1 Diabetes (ALERTT1) examined whether switching from first-generation intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time continuous glucose monitoring (rtCGM) with alert functionality offers additional benefits to adults with type 1 diabetes. The extension of the randomised ALERTT1 trial assessed the effect of switching from isCGM to rtCGM up to 24 months. METHODS: In this 6-month, double-arm, parallel-group, non-masked, randomised, controlled trial, done across six hospitals in Belgium, 254 adults aged 18 years or older with type 1 diabetes previously using isCGM were randomly assigned (1:1) to rtCGM with alerts (intervention; n=127) or isCGM without alerts (control; n=127). Upon completion of the 6-month trial, the control group switched to rtCGM (is-rtCGM group), and the intervention group continued rtCGM (rt-rtCGM group). The extension focused on within-group changes in time in range (TIR; 3·9-10·0 mmol/L; primary outcome), HbA1c, time in clinically significant hypoglycaemia (<3·0 mmol/L), and Hypoglycaemia Fear Survey worry (HFS-worry) score (all prespecified key secondary outcomes). Mean within-group change versus the start of rtCGM is reported, with a positive value referring to a lower value at start of rtCGM. This trial is registered at ClinicalTrials.gov (NCT03772600). FINDINGS: 119 participants were assigned to the is-rtCGM group of whom 112 (94%) completed the 24-month trial, and 123 participants were assigned to the rt-rtCGM group of whom 117 (95%) completed the 24-month trial. TIR increased from 51·8% (95% CI 49·1-54·5) at start of rtCGM (month 6) to 63·5% (60·7-66·3) at month 12 in the is-rtCGM group, and remained stable up to month 24 (change 11·7 percentage points [pp] [9·4-14·0; p<0·0001). In the rt-rtCGM group, TIR increased from 52·5% (95% CI 49·8-55·1) at start of rtCGM (month 0) to 63·0% (60·3-65·8) at month 12, also remaining stable up to month 24 (change 10·5 pp [8·2-12·8]; p<0·0001). HbA1c decreased from 7·4% (57 mmol/mol; month 6) to 6·9% (52 mmol/mol) at month 24 (change -0·54 pp [95% CI -0·64 to -0·44]; -5 mmol/mol [95% CI -6 to -4]; p<0·0001) in the is-rtCGM group, and from 7·4% (57 mmol/mol; month 0) to 7·0% (53 mmol/mol) at month 24 (change -0·43 pp [95% CI -0·53 to -0·33]; -4 mmol/mol [95% CI -5 to -3]; p<0·0001) in the rt-rtCGM group. The change in HFS-worry score was -2·67 (month 24 vs month 6; p=0·0008) in the is-rtCGM group and -5·17 points (month 24 vs month 0; p<0·0001) in the rt-rtCGM group. Time in clinically significant hypoglycaemia was unchanged in both groups after month 12. Severe hypoglycaemia decreased from 31·0 to 3·3 per 100 patient-years after switching to rtCGM. INTERPRETATION: Glycaemic control and hypoglycaemia worry improved significantly up to 24 months after switching from isCGM without alerts to rtCGM with alerts, supporting the use of rtCGM in the care of adults with type 1 diabetes. FUNDING: Dexcom.

The Impact of Baseline User Characteristics on the Benefits of Real-Time Versus Intermittently Scanned Continuous Glucose Monitoring in Adults With Type 1 Diabetes: Moderator Analyses of the ALERTT1 Trial.

BACKGROUND: ALERTT1 showed that switching from intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time CGM (rtCGM) with alert functionality improved time in range (TIR; 70-180 mg/dL), glycated hemoglobin (HbA1c), time <54 mg/dL, and Hypoglycemia Fear Survey version II worry subscale (HFS-worry) score after six months in adults with type 1 diabetes (T1D). Moderator analyses aimed to identify certain subgroups that would benefit more from switching to rtCGM than others. METHODS: Post hoc analyses of ALERTT1 evaluated the impact of 14 baseline characteristics on the difference (delta) in mean TIR, HbA1c, time <54 mg/dL, and HFS-worry score at six months between rtCGM and isCGM. Therefore, the delta was allowed to depend on each of these variables by including interactions in the moderator analysis model. Analyses were performed separately for each variable; variables with P < .10 in the univariable analysis were combined into a single model. RESULTS: Univariable analyses showed no dependency of delta TIR, HbA1c, or time <54 mg/dL on variables other than CGM type. Only delta HFS-worry score depended on baseline HbA1c (P = .0059), indicating less worries with rtCGM in people with baseline HbA1c <6.5% or ≥8%. Given P < .10 for dependency of delta TIR on insulin therapy type (favoring multiple daily injections), baseline HbA1c, and baseline TIR, these variables were combined into a multivariable analysis; interactions were not statistically significant. CONCLUSIONS: Except for HFS-worry score, no interactions between 14 baseline characteristics and the six-month intervention effect of rtCGM on TIR, HbA1c, or time <54 mg/dL were observed, supporting the conclusion of ALERTT1 that switching from isCGM without alerts to rtCGM with alert functionality is beneficial for a wide range of people with T1D.

Quality of Life and Glucose Control After 1 Year of Nationwide Reimbursement of Intermittently Scanned Continuous Glucose Monitoring in Adults Living With Type 1 Diabetes (FUTURE): A Prospective Observational Real-World Cohort Study.

OBJECTIVE: In 2016, nationwide reimbursement of intermittently scanned continuous glucose monitoring (isCGM) for people living with type 1 diabetes treated in specialist diabetes centers was introduced in Belgium. We undertook a 12-month prospective observational multicenter real-world study to investigate impact of isCGM on quality of life and glycemic control. RESEARCH DESIGN AND METHODS: Between July 2016 and July 2018, 1,913 adults with type 1 diabetes were consecutively recruited in three specialist diabetes centers. Demographic, metabolic, and quality of life data were collected at baseline, 6 months, and 12 months of standardized clinical follow-up. The primary end point was evolution of quality of life from baseline to 12 months. Secondary outcome measures were, among others, change in HbA1c, time spent in different glycemic ranges, occurrence of acute diabetes complications, and work absenteeism. RESULTS: General and diabetes-specific quality of life was high at baseline and remained stable, whereas treatment satisfaction improved (P < 0.0001). Admissions for severe hypoglycemia and/or ketoacidosis were rare in the year before study (n = 63 out of 1,913; 3.3%), but decreased further to 2.2% (n = 37 out of 1,711; P = 0.031). During the study, fewer people reported severe hypoglycemic events (n = 280 out of 1,913 [14.6%] vs. n = 134 out of 1,711 [7.8%]; P < 0.0001) or hypoglycemic comas (n = 52 out of 1,913 [2.7%] vs. n = 18 out of 1,711 [1.1%]; P = 0.001) while maintaining HbA1c levels. Fewer people were absent from work (n = 111 out of 1,913 [5.8%] vs. n = 49 out of 1,711 [2.9%]; P < 0.0001). Time spent in hypoglycemia significantly decreased in parallel with less time in range and more time in hyperglycemia. Eleven percent (n = 210) of participants experienced skin reactions, leading to stopping of isCGM in 22 participants (1%). CONCLUSIONS: Nationwide unrestricted reimbursement of isCGM in people with type 1 diabetes treated in specialist diabetes centers results in higher treatment satisfaction, less severe hypoglycemia, and less work absenteeism, while maintaining quality of life and HbA1c.

Dietary restriction and exercise for diabetic patients with chronic kidney disease: a systematic review.

BACKGROUND: Obesity and sedentary lifestyle are major health problems and key features to develop cardiovascular disease. Data on the effects of lifestyle interventions in diabetics with chronic kidney disease (CKD) have been conflicting. STUDY DESIGN: Systematic review. POPULATION: Diabetes patients with CKD stage 3 to 5. SEARCH STRATEGY AND SOURCES: Medline, Embase and Central were searched to identify papers. INTERVENTION: Effect of a negative energy balance on hard outcomes in diabetics with CKD. OUTCOMES: Death, cardiovascular events, glycaemic control, kidney function, metabolic parameters and body composition. RESULTS: We retained 11 studies. There are insufficient data to evaluate the effect on mortality to promote negative energy balance. None of the studies reported a difference in incidence of Major Adverse Cardiovascular Events. Reduction of energy intake does not alter creatinine clearance but significantly reduces proteinuria (mean difference from -0.66 to -1.77 g/24 h). Interventions with combined exercise and diet resulted in a slower decline of eGFR (-9.2 vs. -20.7 mL/min over two year observation; p<0.001). Aerobic and resistance exercise reduced HbA1c (-0.51 (-0.87 to -0.14); p = 0.007 and -0.38 (-0.72 to -0.22); p = 0.038, respectively). Exercise interventions improve the overall functional status and quality of life in this subgroup. Aerobic exercise reduces BMI (-0.74% (-1.29 to -0.18); p = 0.009) and body weight (-2.2 kg (-3.9 to -0.6); p = 0.008). Resistance exercise reduces trunk fat mass (-0,7±0,1 vs. +0,8 kg ±0,1 kg; p = 0,001-0,005). In none of the studies did the intervention cause an increase in adverse events. LIMITATIONS: All studies used a different intervention type and mixed patient groups. CONCLUSIONS: There is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Overall, these interventions have beneficial effects on glycaemic control, BMI and body composition, functional status and quality of life, and no harmful effects were observed.