Automated insulin delivery: benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association.

A technological solution for the management of diabetes in people who require intensive insulin therapy has been sought for decades. The last 10 years have seen substantial growth in devices that can be integrated into clinical care. Driven by the availability of reliable systems for continuous glucose monitoring, we have entered an era in which insulin delivery through insulin pumps can be modulated based on sensor glucose data. Over the past few years, regulatory approval of the first automated insulin delivery (AID) systems has been granted, and these systems have been adopted into clinical care. Additionally, a community of people living with type 1 diabetes has created its own systems using a do-it-yourself approach by using products commercialised for independent use. With several AID systems in development, some of which are anticipated to be granted regulatory approval in the near future, the joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association has created this consensus report. We provide a review of the current landscape of AID systems, with a particular focus on their safety. We conclude with a series of recommended targeted actions. This is the fourth in a series of reports issued by this working group. The working group was jointly commissioned by the executives of both organisations to write the first statement on insulin pumps, which was published in 2015. The original authoring group was comprised by three nominated members of the American Diabetes Association and three nominated members of the European Association for the Study of Diabetes. Additional authors have been added to the group to increase diversity and range of expertise. Each organisation has provided a similar internal review process for each manuscript prior to submission for editorial review by the two journals. Harmonisation of editorial and substantial modifications has occurred at both levels. The members of the group have selected the subject of each statement and submitted the selection to both organisations for confirmation.

Performance of intermittently scanned continuous glucose monitoring systems in people with type 1 diabetes: A pooled analysis.

AIMS: To conduct a pooled analysis to assess the performance of intermittently scanned continuous glucose monitoring (isCGM) in association with the rate of change in sensor glucose in a cohort of children, adolescents, and adults with type 1 diabetes. MATERIAL AND METHODS: In this pooled analysis, isCGM system accuracy was assessed depending on the rate of change in sensor glucose. Clinical studies that have been investigating isCGM accuracy against blood glucose, accompanied with collection time points were included in this analysis. isCGM performance was assessed by means of median absolute relative difference (MedARD), Parkes error grid (PEG) and Bland-Altman plot analyses. RESULTS: Twelve studies comprising 311 participants were included, with a total of 15 837 paired measurements. The overall MedARD (interquartile range) was 12.7% (5.9-23.5) and MedARD differed significantly based on the rate of change in glucose (P < 0.001). An absolute difference of -22 mg/dL (-1.2 mmol/L) (95% limits of agreement [LoA] 60 mg/dL (3.3 mmol/L), -103 mg/dL (-5.7 mmol/L)) was found when glucose was rapidly increasing (isCGM glucose minus reference blood glucose), while a -32 mg/dL (1.8 mmol/L) (95% LoA 116 mg/dL (6.4 mmol/L), -51 mg/dL (-2.8 mmol/L)) absolute difference was observed in periods of rapidly decreasing glucose. CONCLUSIONS: The performance of isCGM was good when compared to reference blood glucose measurements. The rate of change in glucose for both increasing and decreasing glucose levels diminished isCGM performance, showing lower accuracy during high rates of glucose change.

Patient-reported outcomes in adults with type 1 diabetes in global real-world clinical practice: The SAGE study.

AIMS: To conduct a secondary analysis of the SAGE study to evaluate the association between glycaemic control and patient-reported outcomes (PROs), in adults with type 1 diabetes (T1DM) across different age groups and regions. MATERIALS AND METHODS: SAGE was a multinational, cross-sectional, observational study in adults with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64, and ≥65 years), and reported across different regions. PRO questionnaires were applied to assess hypoglycaemia fear (Hypoglycemia Fear Survey-II), diabetes-related distress (Problem Areas In Diabetes questionnaire), insulin treatment satisfaction (Insulin Treatment Satisfaction Questionnaire), and diabetes-specific quality of life (QoL; Audit of Diabetes-Dependent Quality of Life). Multivariable analysis was performed to evaluate the relationship between glycated haemoglobin (HbA1c) target achievement (<7% and individualised targets) with PRO scores. RESULTS: The PRO scores showed relatively low levels of diabetes-related emotional distress and fear of hypoglycaemia, moderate to high treatment satisfaction, and low diabetes-related impact on QoL. Results were generally comparable across age groups with some regional variability. Achievement of the HbA1c <7% target was associated with less worry about hypoglycaemia, lower diabetes-related emotional distress, higher insulin treatment satisfaction, and higher QoL. Achievement of individualised HbA1c targets was associated with lower diabetes-related emotional distress and higher insulin treatment satisfaction. CONCLUSIONS: Better glycaemic control was most closely associated with low emotional distress due to diabetes and high patient-reported insulin treatment satisfaction.

Comparing the accuracy of transcutaneous sensor and 90-day implantable glucose sensor.

BACKGROUND AND AIMS: Continuous glucose monitoring improves glycemic control in diabetes. This study compared the accuracy of the Dexcom G5 Mobile (Dexcom, San Diego, CA) transcutaneous sensor (DG5) and the first version of Eversense (Senseonics,Inc., Germantown, MD) implantable sensor (EVS). METHODS AND RESULTS: Subjects with type 1 diabetes (T1D) and using EVS wore simultaneously DG5 for seven days. At day 3, patients were admitted to a clinical research center (CRC) to receive breakfast with delayed and increased insulin bolus to induce glucose excursions. At CRC, venous glucose was monitored every 15 min (or 5 min during hypoglycemia) for 6 h by YSI 2300 STAT PLUS™ glucose and lactate analyzer. At home patients were requested to perform 4 fingerstick glucose measurements per day. Eleven patients (9 males, age 47.4 ± 11.3 years, M±SD) were enrolled. During home-stay the median [25th-75th percentile] absolute relative difference (ARD) over all CGM-fingerstick matched-pairs was 11.64% [5.38-20.65]% for the DG5 and 10.75% [5.15-19.74]% for the EVS (p-value = 0.58). At CRC, considering all the CGM-YSI matched-pairs, the DG5 showed overall smaller median ARD than EVS, 7.91% [4.14-14.30]% vs 11.4% [5.04-18.54]% (p-value<0.001). Considering accuracy during blood glucose swings, DG5 performed better than EVS when glucose rate-of-change was -0.5 to -1.5 mg/dL/min, with median ARD of 7.34% [3.71-12.76]% vs 13.59% [4.53-20.78]% (p-value<0.001), and for rate-of-change < -1.5 mg/dl/min, with median ARD of 5.23% [2.09-15.29]% vs 12.73% [4.14-20.82]% (p-value = 0.02). CONCLUSIONS: DG5 was more accurate than EVS at CRC, especially when glucose decreased. No differences were found at home.

Diabetic ketoacidosis: A consensus statement of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology and Pediatric Diabetoloy (SIEDP).

BACKGROUND AND AIM: Diabetic ketoacidosis (DKA) is a serious medical emergency once considered typical of type 1 diabetes (T1DM), but now reported to occur in type 2 and GDM patients as well. DKA can cause severe complications and even prove fatal. The aim of our study was to review recent international and national guidelines on diagnosis, clinical presentation and treatment of diabetic ketoacidosis, to provide practical clinical recommendations. METHODS AND RESULTS: Electronic databases (MEDLINE (via PUB Med), Scopus, Cochrane library were searched for relevant literature. Most international and national guidelines indicate the same accurate flow chart to diagnose, to evaluate from clinical and laboratory point of view, and treat diabetic ketoacidosis. CONCLUSION: Prompt diagnosis, rapid execution of laboratory analysis and correct treatment are imperative to reduce the mortality related to diabetic ketoacidosis. These recommendations are designed to help healthcare professionals reduce the frequency and burden of DKA.

Performance of the Steno type 1 risk engine for cardiovascular disease prediction in Italian patients with type 1 diabetes.

BACKGROUND AND AIMS: Premature cardiovascular disease cause excess mortality in type 1 diabetes (T1D). The Steno T1D Risk Engine was developed and validated in northern European countries but its validity in other populations is unknown. We evaluated the performance of the Steno T1D Risk Engine in Italian patients with T1D. MATERIALS AND METHODS: We included patients with T1D with a baseline visit between July 2013 and April 2014, who were free of cardiovascular disease and had complete information to estimate risk. The estimated cardiovascular risk score was compared with the 5-year rate of cardiovascular events by means of logistic regression. RESULTS: Among 223 patients (mean age 43 ± 13 years, 34.5% male, mean duration of diabetes 22 ± 12 years) the mean estimated cardiovascular risk at 5 years was 5.9% (95% C.I. 5.2-6.5%). At baseline, high estimated risk discriminated the presence of asymptomatic atherosclerosis better than microangiopathy, and was not associated with markers of inflammation or endothelial activation. After a mean follow-up of 4.7 ± 0.5 years, only 3 cardiovascular events were observed and nonetheless the risk score was significantly associated with their incidence (OR 1.22; 95% C.I. 1.08-1.39, p = 0.001). However, the observed event rate was significantly lower than the estimated one (3 vs 13; 95% C.I. 12-14; p < 0.001). CONCLUSION: The Steno T1D Risk Score identified subjects with subclinical atherosclerosis and high cardiovascular risk in an Italian T1D population. However, the absolute risk was significantly overestimated. Further studies in larger population are needed to confirm these results.

A High-Fiber Diet Decreases Postabsorptive Protein Turnover but Does Not Alter Insulin Sensitivity in Men with Type 1 Diabetes Mellitus.

BACKGROUND: High-fiber diets (HFDs) are recommended in the diet of persons with diabetes, yet such diets can impair macronutrient digestion and/or absorption, modify insulin sensitivity, and reset metabolism. OBJECTIVES: We studied the effects of a HFD on the kinetics of whole-body protein, a macronutrient that could be affected by dietary fiber, in type 1 diabetes mellitus (T1DM), under both basal-low insulinemic and hyperinsulinemic conditions. METHODS: Eight men with T1DM (body mass index range: 21.8-27.8 kg/m2) were studied twice - before and after the addition of guar gum (∼15 g/d) to their usual diet for ∼4 mo. Whole-body protein degradation (i.e., the rate of appearance [Ra] of endogenous leucine), leucine disposal to protein synthesis (PS), deamination, and reamination, were determined before and after the HFD, both in the postabsorptive state and following a euglycemic, hyperinsulinemic, hyperaminoacidemic clamp, using isotope dilution methods. RESULTS: After the HFD, mean values (± SEs) for postabsorptive leucine Ra decreased by ∼20%: from 2.52 (0.15) to 2.03 (0.16) µmol x kg-1 x min-1, P < 0.049, after vs. before the HFD respectively. PS also decreased, by ∼25%: from 2.03 (0.15) to 1.57 (0.15), P < 0.045. Leucine concentration (P = 0.1) and reamination (P = 0.095) decreased moderately, whereas deamination was unchanged. Following the clamp, plasma amino acid concentrations (P < 0.001), leucine deamination (+ ∼50%, P < 0.00002), reamination (+ ∼30%, P < 0.0007), and PS (+ ∼35%, P < 0.00001) were all increased compared with postabsorptive state values, whereas endogenous leucine Ra was suppressed (by 15%, P < 0.00001, and by 25%, P < 0.001, with the primary or the reciprocal pool models, respectively). No significant differences in these insulin effects before compared with after the HFD were observed. Metabolic control (glycated hemoglobin), daily insulin requirement, and insulin-mediated glucose disposal were unchanged after the HFD. CONCLUSIONS: A HFD downregulates postabsorptive protein turnover in men with T1DM, by decreasing both protein degradation and synthesis, possibly due to a subtle decrease and/or delay in amino acid absorption. It does not significantly affect the insulin (and amino acid sensitivity) to protein turnover, glucose disposal, and metabolic control.

Metabolic control and complications in Italian people with diabetes treated with continuous subcutaneous insulin infusion.

BACKGROUND AND AIM: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). METHODS AND RESULTS: Questionnaires investigating the organisation of diabetes care centres, individuals' clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. <58 mmol/mol for age <18 years and <53 mmol/mol for age >18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. CONCLUSIONS: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. CLINICAL TRIAL REGISTRATION NUMBER: NCT 02620917 (ClinicalTrials.gov).

The GesTIO protocol experience: safety of a standardized order set for subcutaneous insulin regimen in elderly hospitalized patients.

BACKGROUNDS: In non-critical hospitalized patients with diabetes mellitus, guidelines suggest subcutaneous insulin therapy with basal-bolus regimen, even in old and vulnerable inpatients. AIM: To evaluate safety, efficacy, and benefit on clinical management of the GesTIO protocol, a set of subcutaneous insulin administration rules, in old and vulnerable non-ICU inpatients. METHODS: Retrospective, observational study. Patients admitted to Geriatric Clinic of Padua were studied. 88 patients matched the inclusion criteria: type 2 diabetes or hospital-related hyperglycemia, ≥65 years, regular measurements of capillary glycemia, and basal-bolus subcutaneous insulin regimen managed by "GesTIO protocol" for five consecutive days. MAIN OUTCOME MEASURES: ratio of patients with blood glucose (BG) <3.9 mmol/l; number of BG per patient in target range (5-11.1 mmol/l); daily mean BG; and calls to physicians for adjusting insulin therapy. RESULTS: Mean age was 82 ± 7 years. 9.1% patients experienced mild hypoglycaemia, and no severe hypoglycaemia was reported. The median number of BG per patients in target range increased from 2.0 ± 2 to 3.0 ± 2 (p < 0.001). The daily mean BG decreased from 11.06 ± 3.03 to 9.64 ± 2.58 mmol/l (-12.8%, p < 0.005). The mean number of calls to physicians per patient decreased from 0.83 to 0.45 (p < 0.05). CONCLUSIONS: Treatment with GesTIO protocol allows a safe and effective treatment even in very old and vulnerable inpatients with a faster management insulin therapy.

Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems.

Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC) that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively, and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels are suggested that enable the collection of comparator data with these characteristics. This work is an important step toward establishing a future standard for the performance evaluation of CGM systems.

Methods for Insulin Bolus Adjustment Based on the Continuous Glucose Monitoring Trend Arrows in Type 1 Diabetes: Performance and Safety Assessment in an In Silico Clinical Trial.

BACKGROUND: Providing real-time magnitude and direction of glucose rate-of-change (ROC) via trend arrows represents one of the major strengths of continuous glucose monitoring (CGM) sensors in managing type 1 diabetes (T1D). Several literature methods were proposed to adjust the standard formula (SF) used for insulin bolus calculation by accounting for glucose ROC, but each of them provides different suggestions, making it difficult to understand which should be applied in practice. This work aims at performing an extensive in-silico assessment of their performance and safety. METHODS: The methods of Buckingham (BU), Scheiner (SC), Pettus/Edelman (PE), Klonoff/Kerr (KL), Aleppo/Laffel (AL), Ziegler (ZI), and Bruttomesso (BR) were evaluated using the UVa/Padova T1D simulator, in single-meal scenarios, where ROC and glucose at mealtime varied between [-2,+2] mg/dL/min and [80,200] mg/dL, respectively. Efficacy of postprandial glucose control was quantitatively assessed by time in, above and below range (TIR, TAR, and TBR, respectively). RESULTS: For negative ROCs, all methods proved to increase TIR and decrease TAR and TBR vs SF, with KL, PE, and BR being the most effective. For positive ROCs, a general worsening of the performances is present, only BR improved the glycemic control when mealtime glucose was close to hypoglycemia, while SC resulted the safest in the other conditions. CONCLUSIONS: Insulin bolus adjustment methods are effective for negative ROCs, but they generally appear to overdose for positive ROCs, calling for safer strategies in such a scenario. These results can be useful in outlining guidelines to identify which adjustment to apply based on the mealtime condition.

Switching from predictive low glucose suspend to advanced hybrid closed loop control: Effects on glucose control and patient reported outcomes.

AIMS: Automated insulin delivery improves glucose control. Aim of this study was to compare in real life the effects on glucose control and patient reported outcomes of an advanced hybrid closed loop system (Control-IQ), versus a simpler system with predictive low glucose suspend function (Basal-IQ). METHODS: Thirty-one type 1 diabetic subjects were studied during Basal-IQ and after switching to Control-IQ. Variables analyzed were time spent in range (70-180 mg/dL), in tight range (70-140 mg/dL), above range (>180 mg/dL), below range (<70 mg/dL), mean glucose, coefficient of variation and glycated hemoglobin. Questionnaires were administered regarding therapy satisfaction (Diabetes Treatment Satisfaction Questionnaire in status/change form), fear of hypoglycemia (Hypoglycemia Fear Survey), quality of sleep (Pittsburgh Sleep Quality Index). RESULTS: After 12 weeks of Control-IQ, time in range increased from 62.7 to 74.0%, p < 0.0001, time in tight range increased from 37.1 to 44.6 %, p < 0.001, time above range decreased from 35.6 to 24.4% p < 0.0001. Improvements were observed in mean glucose and glucose variability. Glycated hemoglobin decreased from 7.0% (53 mmol/mol) to 6.6% (49 mmol/mol), p < 0.0001. Subjects using Control-IQ manifested greater satisfaction and less fear of hypoglycemia. CONCLUSION: Compared to Basal-IQ, Control-IQ improves glucose control and therapy satisfaction.

Effectiveness of adding alarms to flash glucose monitoring in adults with type 1 diabetes under routine care.

AIM: Whether glucose sensor alarms improve metabolic control and are accepted by individuals with diabetes is unclear. Here, we investigated whether switching from a standard flash glucose monitoring system (FGM1) to a system equipped with hypo- and hyperglycemia alarms (FGM2) improves glycemic control and psychological outcomes in adults with type 1 diabetes (T1D). METHODS: Subjects with T1D and > 4% of time in hypoglycemia or > 40% of time in hyperglycemia were studied while wearing FGM1 (4 weeks) and after switching to FGM2 for 8 weeks. The primary endpoint was the change in time in range (TIR 70-180 mg/dl [3.9-10.0 mmol/L]) after 4 weeks of FGM2 use. Time below range (TBR), time above range (TAR), mean glucose, coefficient of variation (CV), sensor scans, treatment satisfaction, and hypoglycemia fear were secondary outcomes. RESULTS: We included 38 subjects aged 33.7 ± 12.6 year. During 4 weeks of FGM2 use, TIR increased from 52.8 to 57.0% (p = 0.001), TBR decreased from 6.2 to 3.4% (p < 0.0001) as did time < 54 mg/dl (from 1.4 to 0.3%, p < 0.0001) and CV (from 39.6% to 36.1%, p < 0.0001). These changes were confirmed after 8 weeks of FGM2 use. Treatment satisfaction improved and fear of hypoglycemia decreased. Subjects who had > 4% of time in hypoglycemia at baseline showed the greatest improvements in glucose control and treatment satisfaction. CONCLUSION: Switching from FGM1 to FGM2 improved TIR and treatment satisfaction and reduced fear of hypoglycemia. Participants who benefited most from switching from FGM1 to FGM2 were those prone to hypoglycemia.

An Integrated Mobile Platform for Automated Data Collection and Real-Time Patient Monitoring in Diabetes Clinical Trials.

We present a new mobile platform to be used in clinical trials aimed at both collecting data and assessing new technologies and treatments for diabetes care. The main components of the platform are a mobile app, that automatically collects data from continuous glucose monitoring sensors and activity trackers, and also allows users to manually log daily events; a cloud database for safe data storage; a web interface, which allows clinicians to monitor patients' status in real-time. The platform is modular and highly customizable for a multitude of purposes in clinical research. Preliminary tests performed for daily-life data gathering by both clinicians and users are extremely encouraging.

Automated Insulin Delivery: Benefits, Challenges, and Recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association.

A technological solution for the management of diabetes in people who require intensive insulin therapy has been sought for decades. The last 10 years have seen substantial growth in devices that can be integrated into clinical care. Driven by the availability of reliable systems for continuous glucose monitoring, we have entered an era in which insulin delivery through insulin pumps can be modulated based on sensor glucose data. Over the past few years, regulatory approval of the first automated insulin delivery (AID) systems has been granted, and these systems have been adopted into clinical care. Additionally, a community of people living with type 1 diabetes has created its own systems using a do-it-yourself approach by using products commercialized for independent use. With several AID systems in development, some of which are anticipated to be granted regulatory approval in the near future, the joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association has created this consensus report. We provide a review of the current landscape of AID systems, with a particular focus on their safety. We conclude with a series of recommended targeted actions. This is the fourth in a series of reports issued by this working group. The working group was jointly commissioned by the executives of both organizations to write the first statement on insulin pumps, which was published in 2015. The original authoring group was comprised by three nominated members of the American Diabetes Association and three nominated members of the European Association for the Study of Diabetes. Additional authors have been added to the group to increase diversity and range of expertise. Each organization has provided a similar internal review process for each manuscript prior to submission for editorial review by the two journals. Harmonization of editorial and substantial modifications has occurred at both levels. The members of the group have selected the subject of each statement and submitted the selection to both organizations for confirmation.

Efficacy of telemedicine for persons with type 1 diabetes during Covid19 lockdown.

BACKGROUND: Starting March 2020 the Italian Government imposed a lockdown to limit the spread of SARS-CoV-2. During lockdown outpatient visits were limited and telemedicine (TM) was encouraged. METHODS: We retrospectively analyzed data from continuous or flash glucose monitoring systems shared through different cloud systems during the lockdown by subjects with type 1 diabetes and compared data obtained 4 weeks before and 4 weeks after structured telephonic visit. Variables considered were mean glucose, time spent in target (70-180 mg/dl), hypoglycemia (<70 mg/dl) and hyperglycemia (>180 mg/dl), coefficient of variation, and length of sensor use. RESULTS: During the 4 weeks following the telephonic visit there was an improvement of glycemic control, with a significant reduction of mean glucose values (161.1 before vs 156.3 mg/dl after, p = 0.001), an increase of the time spent in target (63.6 vs 66.3, p = 0.0009) and a reduction of time spent in hyperglycemia (33.4 vs 30.5, p = 0.002). No changes were observed regarding glucose variability, time spent in hypoglycemia, and length of sensor use. Similar results were observed in subjects treated with multiple daily injections or continuous subcutaneous insulin infusion. CONCLUSIONS: A structured telephonic visit appears to be an effective way to replace or integrate routine visits in particular conditions.

Comparative Effectiveness of Switching From First-Generation Basal Insulin to Glargine 300 U/ml or Degludec 100 U/ml in Type 1 Diabetes: The RESTORE-1 Study.

INTRODUCTION: Following pivotal trials, real-world evidence is important to assess the impact of new drugs in everyday clinical practice. The RESTORE-1 study aimed to compare effectiveness and safety of the second-generation basal insulins (2BI), i.e., insulin glargine 300 U/ml (Gla-300) vs. degludec 100 U/ml (IDeg-100), in type 1 diabetes (T1D). METHODS: Retrospective, non-inferiority, multicenter study, based on electronic medical records. All patients switching to Gla-300 or IDeg-100 from first-generation basal insulins (1BI) were 1:1 propensity score matched (PSM). Changes during 6 months in HbA1c (primary endpoint), fasting plasma glucose (FPG), body weight, and insulin doses were assessed using linear mixed models for repeated measures. Incidence rates (IR) of hypoglycemic events were assessed. RESULTS: Overall, 19 centers provided data on 585 patients in each PSM cohort. For both groups, statistically significant reductions in HbA1c from baseline to 6 months were documented: - 0.20%; (95% CI - 0.32; - 0.08) in the Gla-300 group and - 0.14%; (95% CI - 0.24; - 0.04) in the IDeg-100 group. The non-inferiority of Gla-300 vs. IDeg-100 was confirmed (non-inferiority margin of 0.30%; upper 95% CI at 6 months, 0.09%). No statistically significant between-group differences emerged in FPG and body weight. Dose changes of basal and short-acting insulin were small in both groups, but higher in the Gla-300 group than in the Deg-100 group (p < 0.006). Incidence rates (IR) of hypoglycemia (blood glucose ≤ 70 mg/dl and < 54 mg/dl) during the 6-month follow-up by treatment were slightly lower in the Gla-300 group than in the Deg-100 group [IR ratios 0.82 (95% CI 0.55; 1.22) and 0.83; (95% CI 0.38; 1.83), respectively]. Hypoglycemic events (blood glucose < 54 mg/dl) decreased at 6 months in both groups (p = 0.01 for Gla-300 and p < 0.001 for IDeg-100). There were no severe hypoglycemic events for Gla-300 and seven events for IDeg-100 (p = 0.02). CONCLUSIONS: Switching from 1BI to 2BI in adults with T1D was associated with similar improvements in glycemic control and overall significant decrease in hypoglycemia, with no severe events with Gla-300. Effectiveness of both insulins was limited by under-titration.

Assessment of the effect of pregnancy planning in women with type 1 diabetes treated by insulin pump.

BACKGROUND: Pregnant women with type 1 diabetes (T1D) have high risk of complications despite improved care based on technology advancements. OBJECTIVE: To assess the effects of pregnancy planning on fetal and maternal outcomes in T1D women treated with continuous subcutaneous insulin infusion (CSII). STUDY DESIGN: We retrospectively assessed maternal and neonatal outcomes in T1D women using CSII who had planned or unplanned pregnancies between 2002 and 2018. The study was done in two European countries with similar sustained programs for pregnancy planning over the study period. RESULTS: Data from 107 pregnancies and newborn babies were collected. Seventy-nine pregnancies (73.8%) had been planned. HbA1c was lower in planned versus unplanned pregnancy before and during all three trimesters of pregnancy (p < 0.0001). Pregnancy planning was associated with a reduction in the occurrence of iatrogenic preterm delivery (RR 0.44, 95% CI 0.23-0.95; p = 0.01). Risk reduction persisted after adjustments for mother's age above 40 years and preeclampsia. High HbA1c before or during pregnancy was associated with an increased risk of iatrogenic preterm delivery (RR 3.05, 95% CI 1.78-5.22, p < 0.0001). Premature newborns needed intensive care more often than those at term (RR 3.10, 95% CI 1.53-4.31; p = 0.002). CONCLUSIONS: Pregnancy planning in T1D women using CSII was associated with better glucose control and decreased risk of iatrogenic preterm delivery. Hence preconception care also improves pregnancy outcome in patients using an advanced mode of insulin delivery. Planned pregnancies could further benefit from the use of new metrics of glucose control.