Target Glucose Range Research Articles

Time in tight range: A key metric for optimal glucose control in the era of advanced diabetes technologies and therapeutics.

Compared to glycated haemoglobin A1c (HbA1c), the rapidly developing continuous glucose monitoring (CGM) technology provides more detailed information about glycemic control. Amongst the new glucose metrics derived from CGM, time in target range of 3.9-10.0 mmol/L (time in range, TIR) has been widely used for the assessment of glucose control. In recent years, the rise of new technologies and therapies including advanced hybrid closed-loop automated insulin delivery systems and new hypoglycemic drugs has made it possible to achieve better glycemic control. In this context, the concept of time in tight range (TITR), defined as the percentage of time spent in target glucose range of 3.9-7.8 mmol/L, has gained increasing attention. Whilst TITR is highly correlated with TIR, there are still differences between the two metrics. These differences make TITR a more appropriate indicator in certain situations, such as when glucose levels are close to normal or when tighter glycemic control is required. This review summarizes recent studies related to TITR.

Novel Protocol for the Use of Advanced Hybrid Closed-Loop System in Adolescents Engaged in Contact Sports.

Managing exercise remains challenging for adolescent athletes with type 1 diabetes (T1D), especially in contact sports. Even the use of hybrid closed loops can cause problems due to the need to disconnect the pump during some training or competitions. This study evaluated the efficacy of a novel protocol for the use of an Advanced Hybrid Closed-Loop System in adolescent football players with T1D during a sports camp. Eleven boys aged 14.9 years (25-75th percentile: 14-15.5), with a diabetes duration of 5.7 years (5.2-7) and regular training schedules in junior football leagues, participated in the study. They started AHCL (MiniMed780G, Medtronic) therapy a month before a week-long sports camp and were observed during the sports camp and the preceding week. Daily camp activities included two 1.5-hour training sessions. Protocol included a 90-minute temporary target of 150 mg/dL before and insulin pump disconnection during training. Physical activity was tracked using wGT3X-BT Actigraph monitors. The camp provided conditions of demanding physical activity (6.6[6-6.9] hours/day of moderate-to-vigorous intensity). After starting AHCL, the average participant time spent in the target glucose range (70-180mg/dL) was 79.34±8.46%, and no significant change was observed during the camp (mean difference +0.79±8.24%, p=0.7581). Median glucose levels dropped by 10.91±12.08mg/dL (p=0.0134), and time in the tight target range increased by 11.41±11.60% (p=0.0008) without increasing the time below range (<70mg/dL) or glycemic variability. During the camp, daily insulin dose and basal/bolus ratio remained comparable with baseline, but the relative amount of automated bolus insulin decreased by 14.24±4.65% (p<0.0001). The predefined regimen, including a temporary target before and disconnection of AHCL during football training, was safe and may provide satisfactory glucose control in active adolescents with T1D. This protocol could be adapted for use in other intensive contact sports.

Impact of Ultra-Rapid Insulin on Boost and Ease-Off in the Cambridge Hybrid Closed-Loop System for Individuals With Type 1 Diabetes.

The objective was to evaluate the safety and efficacy of ultra-rapid-acting insulin with the Boost and Ease-off features of the Cambridge hybrid closed-loop system. A secondary analysis of Boost and Ease-off from two double-blind, randomized, crossover hybrid closed-loop studies comparing (1) Fiasp to insulin aspart (n = 25), and (2) Lyumjev to insulin lispro (n = 26) was carried out. Mean glucose on initialization of Boost and Ease-off, change in glucose 60 and 120 minutes after initialization, duration and frequency of use, mean glucose, and time in, above, and below target glucose range were calculated for periods of Boost use, Ease-off use, or neither. Participants used Boost for longer with Fiasp than insulin aspart (median [interquartile range, IQR] = 75 [53-125] minutes vs 60 [49-75] minutes; P = .01). Mean glucose on Boost initialization with Fiasp was 238 ± 62 mg/dL compared with 218 ± 45 mg/dL with insulin aspart (P = .08). Fiasp use resulted in a greater glucose reduction 120 minutes after Boost initialization [-59 ± 34 mg/dL vs -43 ± 31 mg/dL; P = .02]. There were no statistically significant differences in sensor glucose endpoints during Boost or Ease-off periods between Fiasp and aspart. There were no statistically significant differences during Boost or Ease-off periods when comparing Lyumjev with insulin lispro. There were no safety issues when using Boost and Ease-off with ultra-rapid insulins. The use of Fiasp and Lyumjev during Boost or Ease-off resulted in comparable safety and efficacy to using insulin aspart and lispro.

Predicting the Risk of Adverse Neonatal Outcomes in Women With Insulin-Treated Diabetes: Is It Time for a Pregnancy-Specific Glycemic Risk Index (GRI)?

The Glycemia Risk Index (GRI) describes the quality of glycemic control, emphasizing extreme hypoglycemia and hyperglycemia more than less extreme values. However, a pregnancy-specific GRI (pGRI), tailored to the tighter target glucose range required during pregnancy, has not been established. We retrospectively evaluated clinical, metabolic, and Continuous Glucose Monitoring (CGM) data across pregnancy in women with insulin-treated diabetes, managed between September 2021 and March 2024 at the University Hospital of Pisa. First and second levels of hyperglycemia (TAR1: 140-180 mg/dL, TAR2: >180 mg/dL) and hypoglycemia (TBR1: 63-54 mg/dL, TBR2: <54 mg/dL) were used to calculate the pGRI at each trimester. Logistic regression analysis investigated the association between pGRI and risk of at least one adverse neonatal outcome (among preterm delivery, macrosomia, large for gestational age, small for gestational age, neonatal hypoglycemia, neonatal jaundice, and neonatal intensive care unit admission). Of 45 pregnant women, 25 (56%) experienced at least one adverse neonatal outcome. In the third trimester, women with adverse outcomes had significantly higher total TAR (26 [12-32]% vs 10 [4-23]%, P = .018) and lower TIR (71 [64-83]% vs 88 [75-92]%, P = .007). Specifically, the difference was notable in TAR2 (6 [2-15]% vs 1 [0-4]%, P = .004), whereas TAR1 was comparable between the 2 groups. Accordingly, third trimester pGRI was higher in women with adverse neonatal outcomes (38 [18-49]% vs 18 [10-31]%, P = .013) and, at logistic regression, slightly but significantly increased the risk of adverse neonatal outcomes (1.044 [1.004-1.086], P = .024). Pregnant women with insulin-treated diabetes reporting adverse neonatal outcomes spent more time in hyperglycemia, particularly in extreme hyperglycemia. Therefore, the level of hyperglycemia should always be assessed during pregnancy. The pGRI, emphasizing extreme hyperglycemia, may be a novel comprehensive tool for assessing the risk of adverse neonatal outcomes.

8395 Exploring the Relationship of Dietary Advanced Glycation End-products (AGEs) with Glycemic Control among Adults with Type 1 Diabetes (T1D)

Abstract Disclosure: C.E. Nevarez: None. A.B. Murthy: None. G. Jung: None. B. Gray: None. E. Cagliero: None. V. Aroda: None. E.W. Yu: None. Introduction: Accumulation of advanced glycation end products (AGEs) are thought to play a crucial role in the pathophysiology of diabetic complications, yet the contributions of dietary AGE (dAGE) intake to systemic AGE levels and glycemic control have not been established. Utilizing a newly developed methodology for evaluating dAGEs, our objective was to test whether dAGE impact systemic AGEs and glycemic outcomes in adults with longstanding Type 1 Diabetes (T1D). Methods: We examined adults aged 50+ years participating in the T1D BEACON cohort (n=97 T1D, n=53 non-diabetic controls). We developed a novel algorithm to quantify dietary AGE intake by associating items from the 2014 Block Food Frequency Questionnaire with their AGE content (as determined by ELISA from a previously published dataset; Urribarri et al., 2010). Daily dAGE intake was normalized using the nutrient density method (Willett et al., 1997). Additional measurements included autofluorescent skin AGEs (AGE Reader, DiagnOptics Technologies), diabetic history, hemoglobin A1C and 14-day continuous glucose monitoring to assess percentage time in glucose target range (70-180 mg/dL). We compared dAGEs between T1D and controls and evaluated associations of dAGEs with outcomes using independent t-tests, Pearson’s correlations, and multivariate linear regression with adjustments for age, sex, and body mass index (BMI). Results: Mean age and sex distribution was similar in the T1D and control groups (63.54 ± 6.7 yrs, 50.7% female). BMI was higher in the T1D group (27.9 ± 5.0 vs. 26.0 ± 4.9 kg/m^2, p = 0.031). The mean ± SD duration of diabetes in the T1D cohort was 46.1 ± 9.8 yrs, with A1c of 7.1 ± 1.0%. Utilizing our novel algorithm, the mean daily normalized dAGE intake was higher in the T1D than control groups (8.8 ± 2.3 kU/kcal vs. 7.9 ± 2.5 kU/kcal, p = 0.046) although this did not remain significant after multivariate adjustment (adj p = 0.123). Skin AGEs were higher in the T1D group (3.0 vs 2.5 AU, adj p&amp;lt;0.001). Within the full cohort, dAGE intake was significantly correlated with skin AGEs (r = 0.32, adj. p = 0.003), which was driven primarily by association within the T1D group (r = 0.32, adj p = 0.002). Additionally, dAGE intake was associated with higher A1C values within the full cohort (r = 0.27, adj. p = 0.019), and there was a trend that higher dAGE correlated with decreased time in target glucose range (r = -0.22, adj p = 0.062). Conclusion: Our analyses have revealed novel associations between dAGE intake, skin AGEs, and glycemic outcomes among adults with type 1 diabetes, underscoring the contribution of dietary patterns to systemic AGEs and physiological outcomes within diabetic populations. Future investigations will be needed to validate this novel dAGE assessment in external cohorts and to evaluate the potential impact of dietary AGE intake upon diabetic complications. Presentation: 6/1/2024

Development and Validation of a Nocturnal Hypoglycaemia Risk Model for Patients With Type 2 Diabetes Mellitus.

To develop and test different machine learning algorithms for predicting nocturnal hypoglycaemia in patients with type 2 diabetes mellitus. A retrospective study. We collected data from dynamic blood glucose monitoring of patients with T2DM admitted to the Department of Endocrinology and Metabolism at a hospital in Shanghai, China, from November 2020 to January 2022. Patients undergone the continuous glucose monitoring (CGM) for ≥ 24 h were included in this study. Logistic regression, random forest and light gradient boosting machine algorithms were employed, and the models were validated and compared using AUC, accuracy, specificity, recall rate, precision, F1 score and the Kolmogorov-Smirnov test. A total of 4015 continuous glucose-monitoring data points from 440 patients were included, and 28 variables were selected to build the risk prediction model. The 440 patients had an average age of 62.7 years. Approximately 48.2% of the patients were female and 51.8% were male. Nocturnal hypoglycaemia appeared in 573 (14.30%) of 4015 continuous glucose monitoring data. The light gradient boosting machine model demonstrated the highest predictive performances: AUC (0.869), specificity (0.802), accuracy (0.801), precision (0.409), recall rate (0.797), F1 score (0.255) and Kolmogorov (0.603). The selected predictive factors included time below the target glucose range, duration of diabetes, insulin use before bed and dynamic blood glucose monitoring parameters from the previous day. No Patient or Public Contribution.

Automated Insulin Delivery for Young People with Type 1 Diabetes and Elevated A1c

BackgroundAutomated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels.MethodsIn this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non-automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks.ResultsA total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, −2.5 percentage points; 95% confidence interval [CI], −3.1 to −1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group.ConclusionsIn this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.)

Effects of postprandial exercise timing on blood glucose and fluctuations in patients with type 2 diabetes mellitus.

The aim of this study was to assess how moderate-intensity aerobic exercise performed 45 minutes and 90 minutes after a meal affects blood glucose levels and fluctuations in individuals diagnosed with type 2 diabetes mellitus (T2DM). Twenty-two patients with T2DM, who were solely receiving oral hypoglycemic medication, were enrolled and divided randomly into two categories: those exercising 45 minutes after a meal (45-minute postprandial exercise group) and those exercising 90 minutes post-meal (90-minute postprandial exercise group). Both groups engaged in a 30-minute session of moderate-intensity aerobic stationary bike exercise following breakfast. This aerobic exercise regimen consisted of two stages, with the groups switching exercise timings after the initial phase. Continuous glucose monitoring (CGM) was utilized to evaluate the blood glucose levels and fluctuations in the participants. After breakfast, both overall daily blood glucose levels and the area under the curve for blood glucose following breakfast were reduced in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. The 45-minute postprandial exercise group demonstrated greater time spent within the target glucose range and less time above the target range than the 90-minute postprandial exercise group. Additionally, measures such as standard deviation, mean amplitude of glycemic excursions, largest amplitude of glycemic excursions, and postprandial glucose excursion for breakfast, peak postprandial glucose levels, and duration of elevated glucose levels were all lower in the 45-minute postprandial exercise group compared to the 90-minute postprandial exercise group. Moderate-intensity aerobic exercise lasting 45 minutes after meals was found to be more efficient in decreasing blood glucose levels and minimizing fluctuations compared to exercising 90 minutes after meals in patients with T2DM. Additionally, it notably reduced the peak in blood glucose levels after meals.

Value of Glycemic Indices for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Single-Center Study.

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70-140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier.

Impact of Missed and Late Meal Boluses on Glycemic Outcomes in Automated Insulin Delivery-Treated Children and Adolescents with Type 1 Diabetes: A Two-Center, Population-Based Cohort Study.

Objective: To evaluate the impact of missed or late meal boluses (MLBs) on glycemic outcomes in children and adolescents with type 1 diabetes using automated insulin delivery (AID) systems. Research Design and Methods: AID-treated (Tandem Control-IQ or Medtronic MiniMed 780G) children and adolescents (aged 6-21 years) from Stanford Medical Center and Steno Diabetes Center Copenhagen with ≥10 days of data were included in this two-center, binational, population-based, retrospective, 1-month cohort study. The primary outcome was the association between the number of algorithm-detected MLBs and time in target glucose range (TIR; 70-180 mg/dL). Results: The study included 189 children and adolescents (48% females with a mean ± standard deviation age of 13 ± 4 years). Overall, the mean number of MLBs per day in the cohort was 2.2 ± 0.9. For each additional MLB per day, TIR decreased by 9.7% points (95% confidence interval [CI] 11.3; 8.1), and compared with the quartile with fewest MLBs (Q1), the quartile with most (Q4) had 22.9% less TIR (95% CI: 27.2; 18.6). The age-, sex-, and treatment modality-adjusted probability of achieving a TIR of >70% in Q4 was 1.4% compared with 74.8% in Q1 (P < 0.001). Conclusions: MLBs significantly impacted glycemic outcomes in AID-treated children and adolescents. The results emphasize the importance of maintaining a focus on bolus behavior to achieve a higher TIR and support the need for further research in technological or behavioral support tools to handle MLBs.

Glucose evaluation and management in the ICU (GEM-ICU): Protocol for a bi-centre cohort study.

Hyperglycaemia is common in intensive care unit (ICU) patients. Glycaemic monitoring and effective glycaemic control with insulin are crucial in the ICU to improve patient outcomes. However, glycaemic control and insulin use vary between ICU patients and hypo- and hyperglycaemia occurs. Therefore, we aim to provide contemporary data on glycaemic control and management, and associated outcomes, in adult ICU patients. We hypothesise that the occurrence of hypoglycaemia in acutely admitted ICU patients is lower than that of hyperglycaemia. We will conduct a bi-centre cohort study of 300 acutely admitted adult ICU patients. Routine data will be collected retrospectively at baseline (ICU admission) and daily during ICU stay up to a maximum of 30 days. The primary outcome will be the number of patients with hypoglycaemia during their ICU stay. Secondary outcomes will be occurrence of severe hypoglycaemia, occurrence of hyperglycaemia, time below blood glucose target range, time above target range, all-cause mortality at Day 30, number of days alive without life support at Day 30 and number of days alive and out of hospital at Day 30. Process outcomes include the number of in-ICU days, glucose measurements (number of measurements and method) and use of insulin (including route of administration and dosage). All statistical analyses will be descriptive. This cohort study will provide a contemporary overview of glucose evaluation and management practices in adult ICU patients and, thus, highlight potential areas for improvement through future clinical trials in this area.

Extended-Release Versus Immediate-Release Triamcinolone Acetonide in Patients Who Have Knee Osteoarthritis and Type 2 Diabetes Mellitus

BackgroundIntra-articular corticosteroid injections may cause hyperglycemia (glucose level >180 mg/dL). In a phase 2 study of 33 patients who had osteoarthritis of the knee and type 2 diabetes mellitus, triamcinolone acetonide extended-release (TA-ER) was associated with minimal glycemic control disruption compared with triamcinolone acetonide immediate-release (TA-IR). This post hoc analysis characterizes the clinical relevance of these results. MethodsPatients who had symptomatic osteoarthritis of the knee for ≥6 months, type 2 diabetes mellitus for ≥1 year, and hemoglobin A1c ≥6.5 and ≤9.0% were randomized to receive an intra-articular injection of either TA-ER or TA-IR. Changes in continuous glucose monitor daily glucose level, percentage of time in or above the target glucose range (>70 to 180 mg/dL), time to glucose level 250 mg/dL and maximum glucose level >250 mg/dL, and glycemic variability were evaluated. ResultsAcross postinjection days 1 to 3, the TA-ER group (n = 18) had a lower median change from baseline in maximum glucose level (92.3 versus 169.1 mg/dL), a reduced percentage of time with a glucose level >250 mg/dL (12 versus 26%), a smaller proportion of patients who had a maximum glucose level >250 mg/dL (50 versus 93%), and a greater percentage of time in the target glucose range (62 versus 48%) versus the TA-IR group (n = 15). There was less glycemic variability and lower glucose spikes in the TA-ER versus TA-IR group. Median times to glucose level 250 mg/dL (44 versus 6 hours) and maximum glucose level (34 versus 13 hours) were significantly longer in the TA-ER versus TA-IR group. ConclusionsUse of TA-ER was associated with a clinically meaningful reduction in hyperglycemia versus TA-IR.

Real time continuous glucose monitoring in high-risk people with insulin-requiring type 2 diabetes: A randomised controlled trial.

To investigate the impact of real-time continuous glucose monitoring (rtCGM) on glycaemia in a predominantly indigenous (Māori) population of adults with insulin-requiring type 2 diabetes (T2D) in New Zealand. Twelve-week, multicentre randomised controlled trial (RCT) of adults with T2D using ≥0.2 units/kg/day of insulin and elevated glycated haemoglobin (HbA1c) ≥64 mmol/mol (8.0%). Following a 2-week blinded CGM run-in phase, participants were randomised to rtCGM or control (self-monitoring blood glucose [SMBG]). The primary outcome was time in the target glucose range (3.9-10 mmol/L; TIR) during weeks 10-12, with data collected by blinded rtCGM in the control group. Sixty-seven participants entered the RCT phase (54% Māori, 57% female), median age 53 (range 16-70 years), HbA1c 85 (IQR 74, 94) mmol/mol (9.9 [IQR 8.9, 10.8]%), body mass index (36.7 ± 7.7 kg/m2). Mean (±SD) TIR increased from 37 (24)% to 53 (24)% [Δ 13%; 95% CI 4.2 to 22; P = 0.007] in the rtCGM group but did not change in the SMBG group [45 (21)% to 45 (25)%, Δ 2.5%, 95% CI -6.1 to 11, P = 0.84]. Baseline-adjusted between-group difference in TIR was 10.4% [95% CI -0.9 to 21.7; P = 0.070]. Mean HbA1c (±SD) decreased in both groups from 85 (18) mmol/mol (10.0 [1.7]%) to 64 (16) mmol/mol (8.0 [1.4]%) in the rtCGM arm and from 81 (12) mmol/mol (9.6 [1.1]%) to 65 (13) mmol/mol (8.1 [1.2]%) in the SMBG arm (P < 0.001 for both). There were no severe hypoglycaemic or ketoacidosis events in either group. Real-time CGM use in a supportive treat-to-target model of care likely improves glycaemia in a population with insulin-treated T2D and elevated HbA1c.

The effect of closed-loop glucose control on C-peptide secretion in youth with newly diagnosed type 1 diabetes: the CLOuD RCT

Background We assessed whether a sustained period of intensive glucose control with hybrid closed-loop for 12 months following diagnosis of type 1 diabetes in children and adolescents can preserve C-peptide secretion compared to standard insulin therapy. Methods In an open-label, multicentre, randomised, parallel trial, youth aged 10–16.9 years were randomised within 21 days of type 1 diabetes diagnosis to hybrid closed-loop or standard insulin therapy (control). Primary end point was the difference in mixed-meal C-peptide area under the curve 12 months post diagnosis. Key secondary end points included time spent in target glucose range, glycated haemoglobin and time spent below target glucose range at 12 months. Analysis was by intention to treat. The Closed Loop from Onset in Type 1 Diabetes consortium secured external funding for participants to continue on beyond 12 months, but the funding by National Institute for Health and Care Research and the results reported here refer only to the 12 months follow-up. Results We randomised 97 participants (mean ± standard deviation age 12 ± 2 years), 51 to closed-loop and 46 to control therapy. There was no difference in C-peptide area under the curve at 12 months between groups [geometric mean (interquartile range) closed-loop (n = 46): 0.35 pmol/ml (0.16, 0.49) vs. control (n = 37): 0.46 pmol/ml (0.22, 0.69); mean adjusted difference –0.06 (95% confidence interval –0.14 to 0.03); p = 0.19]. The proportion of time in target range 3.9–10.0 mmol/l based on 14-day masked LibrePro (Abbott Diabetes Care, Maidenhead, UK) sensor glucose data at 12 months was 10 percentage points (95% confidence interval 2 to 17) higher in the closed-loop group (64 ± 14%) compared to control group (54 ± 23%). Arithmetic mean glycated haemoglobin A1c was lower in the closed-loop group by 4 mmol/mol (0.4%) [95% confidence interval 0 to 8 mmol/mol (0.0% to 0.7%)] at 12 months. The mean difference in time spent &lt; 3.9 mmol/l between groups was 0.9 percentage points (95% confidence interval –1.0 to 2.8). Three severe hypoglycaemic events occurred in the closed-loop group (two participants), and one in the control group; one diabetic ketoacidosis occurred in the closed-loop group. Conclusions A sustained period of hybrid closed-loop glucose control following diagnosis of type 1 diabetes in children and adolescents does not slow down the decline in residual C-peptide secretion compared with standard insulin therapy. Despite the lack of effect on C-peptide, glycaemic control was sustained in the closed-loop group, whereas glycaemic control deteriorated in the control group 6 to 9 months after diagnosis and closed-loop safely accommodated the variability in exogenous insulin requirements which occur with beta-cell recovery post diagnosis. Limitations of the study included no central measurement of auto-antibodies at diagnosis. There was imbalance in the rate of diabetic ketoacidosis at diagnosis which is associated with a more rapid decline in C-peptide secretion, but this was adjusted for in the analyses. This highlights the need for improved therapies to allow youth to achieve recommended glycaemic targets from onset of type 1 diabetes irrespective of the lack of effect on residual C-peptide secretion. Future work includes ongoing follow-up of the study population for up to 4 years after diagnosis to observe how any differences in glycaemic control between treatment groups develop over time. Trial registration This trial is registered as Clinicaltrials.gov NCT02871089. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 14/23/09), the Helmsley Trust (2016PG-T1D045 and 2016PG-T1D046), and JDRF (22-2013-266 and 2-RSC-2019-828-M-N), and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 8. See the NIHR Funding and Awards website for further award information. Additional support for the artificial pancreas work was from the NIHR Cambridge Biomedical Research Centre and NIHR Oxford Biomedical Research Centre. Abbott Diabetes Care supplied free glucose monitoring devices, and Dexcom supplied discounted continuous glucose monitoring devices. Medtronic supplied discounted insulin pumps, phone enclosures, continuous glucose monitoring devices, and pump consumables.

Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial

Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. Diabetes Liga Research Fund and Medtronic.

Evaluating the efficacy and safety of weekly Insulin Icodec vs. Daily Insulin Glargine in type 2 Diabetes Mellitus: a systematic review and meta-analysis.

Various insulin therapies for Diabetes Mellitus offer different benefits while having potential risks. We aim to compare Insulin Icodec, a novel Insulin analogue with the ease of once-weekly administration, to the once-daily Insulin Glargine U100 regarding glycemic control and safety profile. We performed a systematic literature search of electronic databases for peer-reviewed articles from inception until September 1 2023. A total of 2215 type 2 diabetic patients were included, of which 1209 received Insulin Icodec and1048 recieved Insulin Glargine U100. In terms of glycemic control, Insulin Icodec showed a significantly longer time in the target glucose range (MD: 0.304, CI: 0.069, P = 0.000) and a more significant reduction in HbA1c (MD: -0.154, CI: 0.003, P = 0.005) compared to Insulin Glargine U100. Fasting Plasma Glucose did not differ significantly. Insulin Icodec led to a more significant increase in body weight (MD: 0.161kg, P = 0.029), while Insulin Glargine required a higher insulin dose (MD: 1.920IU, P = 0.000). Regarding safety, the two groups had no significant differences in hypoglycemic events or adverse outcomes. Once-weekly Insulin Icodec demonstrates superior glycemic control with a reduced HbA1c compared to Once-Daily Insulin Glargine U100 while maintaining similar safety profiles. The online version contains supplementary material available at 10.1007/s40200-024-01431-5.

Automated closed-loop insulin delivery for the management of type 1 diabetes during pregnancy: the AiDAPT RCT

Background There are over 2000 pregnancies annually in women with type 1 diabetes in the UK. Despite recent improvements in diabetes technology, most women cannot achieve and maintain the recommended pregnancy glucose targets. Thus, one in two babies experience complications requiring neonatal care unit admission. Recent studies demonstrate that hybrid closed-loop therapy, in which algorithms adjust insulin delivery according to continuous glucose measurements, is effective for managing type 1 diabetes outside of pregnancy, but efficacy during pregnancy is unclear. Objective To examine the clinical efficacy of hybrid closed-loop compared to standard insulin therapy in pregnant women with type 1 diabetes. Design A multicentre, parallel-group, open-label, randomised, controlled trial in pregnant women with type 1 diabetes. Setting Nine antenatal diabetes clinics in England, Scotland and Northern Ireland. Participants Pregnant women with type 1 diabetes and above-target glucose levels, defined as glycated haemoglobin A1c of ≥ 48 mmol/mol (6.5%) in early pregnancy. Interventions A hybrid closed-loop system compared to standard insulin delivery (via insulin pump or multiple daily injections) with continuous glucose monitoring. Outcome measures The primary outcome is the difference between the intervention and control groups in percentage time spent in the pregnancy glucose target range (3.5–7.8 mmol/l) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Secondary outcomes include overnight time in range, time above range (&gt; 7.8 mmol/l), glycated haemoglobin A1c, safety outcomes (diabetic ketoacidosis, severe hypoglycaemia, adverse device events), psychosocial functioning obstetric and neonatal outcomes. Results The percentage of time that maternal glucose levels were within target range was higher with closed-loop than standard insulin therapy: 68.2 ± 10.5 in closed-loop and 55.6 ± 12.5 in the control group (mean‑adjusted difference 10.5 percentage points, 95% confidence interval 7.0 to 14.0; p &lt; 0.001). Results were consistent in secondary outcomes, with less time above range (−10.2%, 95% confidence interval −13.8 to −6.6%; p &lt; 0.001), higher overnight time in range (12.3%, 95% confidence interval 8.3 to 16.2%; p &lt; 0.001) and lower glycated haemoglobin A1c (−0.31%, 95% confidence interval −0.50 to −0.12%; p &lt; 0.002) all favouring closed-loop. The treatment effect was apparent from early pregnancy and consistent across clinical sites, maternal glycated haemoglobin A1c categories and previous insulin regimen. Maternal glucose improvements were achieved with 3.7 kg less gestational weight gain and without additional hypoglycaemia or total daily insulin dose. There were no unanticipated safety problems (six vs. five severe hypoglycaemia cases, one diabetic ketoacidosis per group) and seven device-related adverse events associated with closed-loop. There were no between-group differences in patient-reported outcomes. There was one shoulder dystocia in the closed-loop group and four serious birth injuries, including one neonatal death in the standard care group. Limitations Our results cannot be extrapolated to closed-loop systems with higher glucose targets, and our sample size did not provide definitive data on maternal and neonatal outcomes. Conclusions Hybrid closed-loop therapy significantly improved maternal glycaemia during type 1 diabetes pregnancy. Our results support National Institute for Health and Care Excellence guideline recommendations that hybrid closed-loop therapy should be offered to all pregnant women with type 1 diabetes. Future work Future trials should examine the effectiveness of hybrid closed-loop started before pregnancy, or as soon as possible after pregnancy confirmation. Trial registration This trial is registered as ISRCTN56898625. Funding This award was funded by the National Institute of Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 16/35/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 7. See the NIHR Funding and Awards website for further award information. Dexcom supplied the continuous glucose monitoring systems used by AiDAPT intervention- and control-arm participants at reduced cost.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Glycemic Outcomes with Closed-Loop Insulin Delivery.

The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9-10.0 mmol/L (70-180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis.

Safety and Efficacy of Insulins in Critically Ill Patients Receiving Continuous Enteral Nutrition

ObjectiveThere is a relative lack of consensus regarding the optimal management of hyperglycemia in patients receiving continuous enteral nutrition (EN), with or without a diagnosis of diabetes. MethodsThis retrospective study examined 475 patients (303 with known diabetes) hospitalized in critical care setting units in 2019 in a single center who received continuous EN. Rates of hypoglycemia, hyperglycemia, and glucose levels within the target range (70-180 mg/dL) were compared between patients with and without diabetes, and among patients treated with intermediate-acting (IA) biphasic neutral protamine Hagedorn 70/30, long-acting (LA) insulin, or rapid-acting insulin only. ResultsAmong those with type 2 diabetes mellitus, IA and LA insulin regimens were associated with a significantly higher proportion of patient-days in the target glucose range and fewer hyperglycemic days. Level 1 (<70 mg/dL) and level 2 (<54 mg/dL) hypoglycemia occurred rarely, and there were no significant differences in level 2 hypoglycemia frequency across the different insulin regimens. ConclusionAdministration of IA and LA insulin can be safe and effective for those receiving insulin doses for EN-related hyperglycemia.

Insulin Infusion Protocols for Blood Glucose Management in Critically Ill Patients: A Scoping Review.

Continuous insulin infusion is a method for maintaining blood glucose stability in critically ill patients with hyperglycemia. Many insulin infusion protocols have been applied in intensive care units. Understanding the content of these protocols can help clinical staff choose the most appropriate and convenient protocol and promote best practices in managing glucose levels in critically ill adult patients. To examine the types of insulin infusion therapies performed for blood glucose management in critically ill patients. For this scoping review, 3 Chinese-language and 8 English-language databases were searched for articles published from May 25, 2016, to October 25, 2022. Twenty-one articles met the inclusion criteria. Twenty-one insulin infusion protocols were examined. Most of the insulin infusion protocols were paper protocols. Fourteen glucose management indicators were included in the 21 protocols. The glucose target range for all 21 protocols ranged from 70 to 180 mg/dL (3.9-10.0 mmol/L). Nurses were primarily responsible for protocol implementation in most protocol development processes. The roles of nurses differed in nurse-led insulin infusion protocols and non-nurse-led insulin infusion protocols. This scoping review indicates an urgent need for more comprehensive glycemic control guidelines for patients receiving critical care. Because insulin infusion protocols are core aspects of blood glucose management guidelines, different population subgroups should also be considered. Nurse-led guidelines must be based on the best available evidence and should include other variables related to glucose management (eg, patient disease type, medication, and nutrition) in addition to insulin infusion.