Efficacy and safety of sensor augmented insulin pump therapy with low-glucose suspend feature in older adults: A retrospective study in Bogota, Colombia.

BACKGROUND AND AIMS: The literature has supported the efficacy and safety of insulin pump therapy in young adults diagnosed with type 1 diabetes (DM1). However, there is limited evidence in older adults with DM1 and DM2. METHODS: A retrospective cohort study was conducted in patients ≥60 years-old with DM1 and DM2, who started Sensor Augmented Insulin Pump therapy with low-glucose suspend feature (SAP + LGS) at Hospital Universitario San Ignacio diabetes center in Bogotá, Colombia. Patients were evaluated between 2009 and 2019 and were treated with Paradigm VEO or Medtronic MiniMed 640 insulin pumps and continuous glucose monitoring system. Glycated hemoglobin (A1c), severe hypoglycemia and hypoglycemia unawareness were assessed at least every 3 months, and hospitalizations and ketoacidosis episodes incidence were assessed yearly. RESULTS: 36 patients were analyzed, (67.36 ± 4.88 years-old) (body mass index 25.48 ± 4.61 kg/m2). The most common indications for starting SAP + LGS were hypoglycemia (58.3%), high glycemic variability (25.0%) and poor metabolic control (16.7%). 26 patients used VEO (72.2%) whereas 27.8% started 640 insulin pump. Data from 32 participants showed A1c decreased from 8.57 ± 1.73% to 7.42 ± 0.96 after a year of therapy (Mean difference -1.15%, p < 0.05); 28.12% reached A1c levels <7% and 42.85% < 7.5%. There was a significant decrease in the proportion of patients with at least one severe hypoglycemia (56.7 vs 3.3%), one or more hospitalizations (20 vs 3.3%), and hypoglycemia unawareness after the first year of follow-up (p < 0.05). CONCLUSIONS: These results suggest that SAP + LGS is safe and effective in people 60 years or older after one year of therapy. Future randomized clinical trials are needed in the elderly.

Lower versus standard sucrose dose for treating hypoglycemia in patients with type 1 diabetes mellitus in therapy with predictive low glucose suspend (PLGS) augmented insulin pumps: A randomized crossover trial in Santiago, Chile.

BACKGROUND AND AIMS: Recommended hypoglycemia treatment in adults with T1D consists of 15 g of rapid absorption carbohydrates. We aimed to evaluate the response to fewer carbohydrates for treating hypoglycemia in patients with T1D on insulin pumps with predictive suspension technology (PLGS). METHODS: T1D patients on insulin pumps with PLGS were randomized to receive 10 or 15 g of sucrose per hypoglycemia for two weeks (S10 and S15 groups, respectively) when capillary blood glucose (BG) was <70 mg/dL, with crossover after two weeks. Evolution of capillary BG, active insulin, and suspension time were assessed. RESULTS: 59 hypoglycemic episodes were analyzed, 33 in S10 and 26 in S15. Baseline BG in S10 was 54.3 ± 7.7 mg/dL versus 56.9 ± 8.8 in S15 (p = 0,239). Active insulin, present in 85% of the episodes, and PLGS suspension time were similar between groups. BG at 15 min was 77 mg/dL in S10 and 95 mg/dL in S15 (p = 0.0007). In S10, 21% of the episodes required to repeat the treatment after 15 min compared with none on S15, with a RR of 0,79 (95% CI 0.66, 0.940, p = 0,014) for successfully treating the episode. Sensor glucose was significantly different from BG at the moment of the hypoglycemia and control 15 min after treatment. No severe hypoglycemia and no rebound hyperglycemia occurred in neither group. CONCLUSIONS: A hypoglycemia treatment protocol with a lower dose of sucrose might be insufficient despite PLGS technology. Our data suggest that standard doses of sucrose should still be recommended.

A prospective randomized trial comparing computerized columnar insulin dosing chart (the Atlanta protocol) versus the joint British diabetes societies for inpatient care protocol in management of hyperglycemia in patients with acute coronary syndrome admitted to cardiac care unit in Alexandria, Egypt.

BACKGROUND: Hyperglycemia in acute coronary syndrome (ACS) is linked to raised morbidity and mortality. Insulin administration using insulin infusion protocols (IIP) is the preferred strategy to control hyperglycemia in critically ill patients. To date, no specific IIP has been identified as the most efficient for achieving glycemic control. AIM: to compare glycemic achievements (safety) (primary objective), and coronary and other clinical outcomes (efficacy) (secondary objective) by hyperglycemia management in Cardiac Care Unit (CCU) using computerized Atlanta Protocol (Group (I)) versus paper-based Joint British Diabetes Societies (JBDS) For Inpatient Care Protocol (Group (II)). PATIENTS AND METHODS: The study was done on 100 ACS patients admitted to Alexandria Main University hospital CCU with RBG >180 mg/dL. They were randomized into the 2 groups in a 1:1 ratio. CBG was measured hourly for 72 hours and was managed by IV insulin infusion. RESULTS: Group (I) showed statistically significant less mean time for target BG achievement (3.52 ± 1.53hours), lower incidence of Level 1 hypoglycemia (2%) than Group (II) (4.76 ± 2.33 hours, 22%, p = 0.013, 0.002 respectively) and statistically significant less mean number of episodes above the glycemic target after its achievement than Group (II) (p < 0.001). Regarding Level 2 hypoglycemia the difference was not significant statistically. CONCLUSION: Both protocols successfully maintained target BG level with low incidence of clinically significant hypoglycemia, however, the computerized Atlanta protocol achieved better glycemic outcomes. We recommend the use of the computerized Atlanta protocol in CCU rather than JBDS for Inpatient Care Protocol whenever this is feasible.

Treatment and long-term follow-up of patients diagnosed with type 1 diabetes mellitus before age 5.

OBJECTIVES: This study aimed to determine the effects of continuous subcutaneous insulin infusion (CSII) treatment on anthropometric measurements, mean HbA1c, and insulin dosage in patients diagnosed under 5 years of age and compare with multiple-dose injection therapy (MDI). METHODS: Children with type 1 diabetes mellitus, diagnosed <5 years since 2000 and their 19-year follow-up were evaluated retrospectively. Weight, height, body mass index (BMI), blood pressure, and HbA1c values were recorded for each visit. RESULTS: Hundred and five patients (58.1% female, 41.9% male) were included in the study. Sixty-three (60 %) patients were treated by CSII and 42 (40%) by MDI. Mean age at diagnosis was 2.68 ± 1.42 and 3.29 ± 1.30 years respectively. Mean follow-up was 7.42 ± 4.76 and 6.01 ± 4.41 years respectively. For each group, weight standard deviation score (SDS) increased significantly in the first year after the diagnosis (p<0.001), and with the onset of puberty weight SDS decreased significantly (p<0.001). The trend of weight and BMI SDS changes over the years showed similar characteristics in both groups. During follow-up height SDS was similar in both groups except in Tanner stage 5. When puberty was completed, mean height SDS was 0.51 ± 1.03 in CSII and -0.31 ± 0.75 in the MDI group (p: 0.029). Mean HbA1c was significantly lower in the CSII group (7.62 ± 0.82 and 8.17 ± 1.22 respectively). Systolic and diastolic blood pressure change trends during the follow-up were also similar in both groups. CONCLUSIONS: CSII treatment had positive effects on metabolic control and height SDS in patients with early-onset diabetes without increasing BMI.

Initial Basal and Bolus Rates and Basal Rate Variability During Pump Treatment in Children and Adolescents

Objective: Pump-treated children with type 1 diabetes (T1DM) have widely differing basal insulin (BI) infusion profiles for specific periods of the day. The pattern of BI requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates. However, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of this study was to analyze the change of the initial, equally distributed, BI rates over the first year of standard insulin pump therapy. Methods: A total of 154 patients with T1DM, aged between 0 and <21 years at diagnosis, from a single center were documented. Patients were divided into five age groups according to age at pump initiation: group 1, <5 years (n=36); group 2, 5-8 years (n=20); group 3, 8-15 years (n=74); group 4, 15-18 years, (n=19); and group 5, >18 years, (n=5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated. Results: Median (range) age and diabetes duration was 14.46 (1.91-26.15) and 7.89 (1.16-17.15) years, respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg in the whole cohort at the initiation and after one year of pump therapy was 0.86±0.23 U/kg and 0.78±0.19 U/kg, respectively and differed significantly between each age group (p<0.001; p<0.001). Mean daily basal rate/kg showed significant differences between the five groups (p<0.001). Circadian distribution of BI differed markedly among the five age groups. Conclusion: At the initiation of insulin pump therapy, circadian profiles by age group should be taken into account in pediatric patients to optimize basal rate faster and more easily.

Continuous subcutaneous insulin infusion does not correspond with pregnancy outcomes despite better glycemic control as compared to multiple daily injections in type 1 diabetes - Significance of pregnancy planning and prepregnancy HbA1c.

OBJECTIVE: The aim of the study was to compare pregnancy outcomes with glycemic control, total increase in insulin requirement, and body weight gain in the women with Type 1 Diabetes Mellitus (T1DM) using continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). MATERIAL AND METHODS: This was a single center retrospective observational study involving 209 pregnant Caucasian women. Among the study participants, 95 subjects were treated with MDI and 114 patients were using CSII therapy. The primary outcomes were pregnancy results, while secondary ones were HbA1c, increase in daily dose of insulin (DDI), and body weight gain. RESULTS: At baseline, the CSII users were older (P = 0.0373), they were diagnosed with T1DM at a younger age (P = 0.047), and more often planned pregnancy (P = 0.032). A majority of the women were classified as class D, according to the White classification. Among the CSII users, a significantly higher proportion of the subjects in class B was noted than in the MDI users, with no differences in the proportion of the remaining White classes. Prepregnancy HbA1c was insignificantly lower in the CSII group, however, a significantly higher proportion of the CSII users reached the target value of HbA1c (P = 0.008). A prepregnancy daily dose of insulin (both total and per kg of body weight), body weight, and body mass index (BMI) did not differ between the groups. The 1st and 2nd trimester HbA1c was lower among the CSII users (6.83 ± 1.38 vs 7.52 ± 2.11%, P = 0.01 and 6.17 ± 0.9 vs 6.57 ± 1.12%, P = 0.009, respectively), while the 3rd trimester HbA1c as well as the total change in HbA1c were comparable. Neither DDI and body weight in concecutive trimesters, nor their total gestational increase, differed between the groups. The rate of pregnancy loss, such as abortions, fetal and neonatal death did not differ between the groups. As regards composite pregnancy loss, prepregnancy HbA1c was 8.41%±2.81% among the MDI cohort vs 7.22%±1.31% in the CSII users (P = 0.517). No differences were found in the gestational age at delivery, the mode of delivery, neonatal birth weight, the rate of macrosomy, LGA or SGA. A higher Apgar score was noted among the CSII users (8.63 ± 1.63 vs 8.03 ± 2.49%, P = 0.047), however, the proportion of neonates with an Apgar score lower than 7 points was similar. In the women planning pregnancy, as compared to the subjects who did not, HbA1c was significantly lower in the 1st trimester, together with a significantly higher rate of the women achieving the target HbA1c value during planning as well as in the 1st trimester. In the group of women planning pregnancy, significantly lower 1st trimester HbA1c and composite outcome of pregnancy loss were observed in the CSII users vs the MDI treated women. Lack of pregnancy planning and a high HbA1c level in the 1st trimester were independent predictors of both LGA (OR = 4.99 [95%CI 1.12-21.0], P = 0.033 and OR = 3.02 [95%CI 1.19-7.65], P = 0.019, respectively) and macrosomia (OR = 8.43 [95%CI 1.36-51.93], P = 0.021 and OR = 5.47 [95%CI 1.77-16.87], P = 0.003, respectively). CONCLUSIONS: The course of pregnancy and obstetric outcomes were not dependent on the mode of insulin delivery, but only on pregnancy planning and HbA1c in early pregnancy. Further studies are needed to explore more precise parameters describing both glycemic control in pregnant women as well as perinatal infant well-being.

Effectiveness and equity of continuous subcutaneous insulin infusions in pediatric type 1 diabetes: A systematic review and meta-analysis of the literature.

AIMS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) and non-randomized studies (NRS) to assess the effectiveness and equity of continuous subcutaneous insulin infusions (CSII) versus multiple-daily injections (MDI) on glycemic outcomes. METHODS: Searches were conducted between 2000 and 2019 in MEDLINE, CENTRAL, EMBASE and HTA. Included studies compared the CSII vs MDI in children and young people (CYP) ≤ 20 years with type 1 diabetes. Two independent reviewers screened the articles, extracted the data, assessed the risk of bias, evaluated the quality of evidence, and identified equity data. Results were pooled with a random-effects model. RESULTS: Of the 578 articles screened, 16 RCT (545 CYP on CSII) and 70 NRS (73253 on CSII) were included in the meta-analysis. There was moderate-level evidence that the CSII lower HbA1c in RCT (pooled mean difference [MD]: -0.22%; 95% confidence interval [CI]: -0.33, -0.11%; I2:34%) and insufficient in NRS (pooled MD: -0.45%; 95%CI: -0.52, -0.38%; I2:99%). The pooled incidence rate ratio of severe hypoglycemia on CSII vs MDI in RCT was 0.87 (95%CI: 0.55, 1.37; I2:0%; low-level evidence), and 0.71 (95%CI: 0.63, 0.81; I2:57%, insufficient evidence) in NRS. Health-related quality of life presented insufficient evidence. Equity data were scarcely reported. CONCLUSIONS: CSII modestly lower HbA1c when compared with MDI. Current literature does not provide adequate data on other glycemic outcomes. Future assessment on diabetes technology should include individual and area-level socioeconomic data. The study protocol was pre-registered in PROSPERO (CRD42018116474).

The Predictive Low Glucose Management System in Prevention of Clinically Significant Hypoglycemia in Type 1 Diabetes. A Preliminary Study Identifying the Most Common Events Leading Up to Hypoglycemia During Insulin Pump Therapy.

BACKGROUND/AIM: Prevention of hypoglycemia remains a major challenge in diabetic management, despite the introduction of modern insulin pumps in daily clinical practice. The Low Glucose Suspend (LGS) and the newer Predictive Low Glucose Management (PLGM) systems incorporated in the Medtronic insulin pumps have shown promising results in prevention of hypoglycemia. Our aim was to evaluate the effect of the 2 systems relative to the frequency of clinically significant hypoglycemia in Type 1 diabetes (T1DM). In addition, we investigated the events preceding clinically significant hypoglycemia episodes. METHODS: A cross-sectional study was conducted in 30 T1DM patients using the MiniMed 640G vs. 30 using the MiniMed Veo sensor-augmented insulin pump. All data was recorded during patients' normal daily activity and living conditions. The patients were matched for age and duration of diabetes. RESULTS: PLGM use was associated with lower incidence of clinically significant hypoglycemia (1.9±1.4 vs. 3.6±1.9 episodes per week), along with reduced exposure to hypoglycemia. The data indicated that both pump systems are effective in preventing severe hypoglycemic episodes. In both groups the most common events preceding hypoglycemic episodes included adjustment of hyperglycemia, basal rate increase and miscalculation of carbohydrates. CONCLUSIONS: The results indicated that the use of the Minimed 640G pump system can help reduce the frequency of clinically significant hypoglycemia. Management of hyperglycemia must be addressed in diabetes education programs in order to encourage proper adjustment of high blood glucose levels. Future studies would be useful in exploring the details of the events preceding hypoglycemia episodes in insulin pump users.

Revision of Alberta's Provincial Insulin Pump Therapy Criteria for Adults and Children With Type 1 Diabetes: Process, Rationale and Framework for Evaluation.

OBJECTIVES: Insulin pump therapy is a valuable, but costly approach, with public funding in Alberta for eligible individuals since 2013. The Provincial Insulin Pump Therapy Program Clinical Advisory Committee has revised and updated the clinical criteria, integrating current literature, best practice and feedback from clinicians. The objective was to develop criteria that would: 1) optimize safety and effectiveness of insulin pump therapy, while 2) carefully stewarding resources available to care for people with type 1 diabetes. METHODS: The Clinical Advisory Committee comprised health-care professionals with expertise in pump therapy and included adult and pediatric endocrinologists, an internist, a pediatrician, certified pump trainers, diabetes educators and clinic managers. The group meets regularly by teleconference. Decisions are made by consensus. RESULTS: Indications for insulin pump therapy for adults and children with insulin-deficient diabetes were divided into 4 hierarchical levels: 1) problematic hypoglycemia, inability to achieve acceptable control or progressive complications; 2) unpredictable activity, dawn phenomenon or children for whom use of multiple daily injections is not appropriate; 3) individual preference and 4) clinical exception, with priority given to indications with clear evidence of benefit. The criteria emphasize the importance of: 1) adequate education in diabetes self-management; 2) adequate trial of flexible insulin therapy with modern analogues and 3) evidence of active, safe diabetes self-management. Tools to facilitate effective and efficient annual review and surveillance were developed incorporating biological, behavioural evaluation and self-reflection to provide a framework for program evaluation. The recommendations were implemented in January 2019. CONCLUSIONS: The process and revised criteria may be valuable for jurisdictions considering how to develop and implement a publicly funded insulin pump program.

Glucose Control During Physical Activity and Exercise Using Closed Loop Technology in Adults and Adolescents with Type 1 Diabetes.

Guidelines for safe exercise strategies exist for both pediatric and adult patients living with type 1 diabetes. The management of type 1 diabetes during exercise is complex, but making insulin dosing adjustments in advance of activity can yield positive outcomes and reduce the likelihood of hypoglycemia. Closed loop (also known as automated insulin delivery) systems are able to partially automate insulin delivery and can assist in exercise and overall management of type 1 diabetes. Current exercise guidelines, however, focus primarily on management strategies for patients using multiple daily injections or open loop insulin pump therapy. Closed loop systems require strategic approaches to type 1 diabetes management, including appropriate timing and duration of exercise targets and carbohydrates around exercise that have yet to be standardized. This review aims to showcase how closed loop technology has evolved over the last decade and summarizes a number of closed loop and exercise studies both in free-living conditions and clinical trials. This review also highlights strategies and approaches for exercise and type 1 diabetes management using closed loop systems. Some differences in closed loop strategies for exercise include the importance of pump suspension if disconnecting during exercise, fewer grams of uncovered carbohydrates before exercise and these should be taken close to exercise onset to avoid a rise in automated insulin delivery. A primary goal for future closed loop systems is to detect exercise without user input, so that patients are not required to preset exercise targets well in advance of activity, as are the current recommendations.

Continuous Glucose Monitors and Automated Insulin Dosing Systems in the Hospital Consensus Guideline.

This article is the work product of the Continuous Glucose Monitor and Automated Insulin Dosing Systems in the Hospital Consensus Guideline Panel, which was organized by Diabetes Technology Society and met virtually on April 23, 2020. The guideline panel consisted of 24 international experts in the use of continuous glucose monitors (CGMs) and automated insulin dosing (AID) systems representing adult endocrinology, pediatric endocrinology, obstetrics and gynecology, advanced practice nursing, diabetes care and education, clinical chemistry, bioengineering, and product liability law. The panelists reviewed the medical literature pertaining to five topics: (1) continuation of home CGMs after hospitalization, (2) initiation of CGMs in the hospital, (3) continuation of AID systems in the hospital, (4) logistics and hands-on care of hospitalized patients using CGMs and AID systems, and (5) data management of CGMs and AID systems in the hospital. The panelists then developed three types of recommendations for each topic, including clinical practice (to use the technology optimally), research (to improve the safety and effectiveness of the technology), and hospital policies (to build an environment for facilitating use of these devices) for each of the five topics. The panelists voted on 78 proposed recommendations. Based on the panel vote, 77 recommendations were classified as either strong or mild. One recommendation failed to reach consensus. Additional research is needed on CGMs and AID systems in the hospital setting regarding device accuracy, practices for deployment, data management, and achievable outcomes. This guideline is intended to support these technologies for the management of hospitalized patients with diabetes.

Use of Factory-Calibrated Real-time Continuous Glucose Monitoring Improves Time in Target and HbA1c in a Multiethnic Cohort of Adolescents and Young Adults With Type 1 Diabetes: The MILLENNIALS Study.

OBJECTIVE: International type 1 diabetes registries have shown that HbA1c levels are highest in young people with type 1 diabetes; however, improving their glycemic control remains a challenge. We propose that use of the factory-calibrated Dexcom G6 CGM system would improve glycemic control in this cohort. RESEARCH DESIGN AND METHODS: We conducted a randomized crossover trial in young people with type 1 diabetes (16-24 years old) comparing the Dexcom G6 CGM system and self-monitoring of blood glucose (SMBG). Participants were assigned to the interventions in random order during two 8-week study periods. During SMBG, blinded continuous glucose monitoring (CGM) was worn by each participant for 10 days at the start, week 4, and week 7 of the control period. HbA1c measurements were drawn after enrollment and before and after each treatment period. The primary outcome was time in range 70-180 mg/dL. RESULTS: Time in range was significantly higher during CGM compared with control (35.7 ± 13.5% vs. 24.6 ± 9.3%; mean difference 11.1% [95% CI 7.0-15.2]; P < 0.001). CGM use reduced mean sensor glucose (219.7 ± 37.6 mg/dL vs. 251.9 ± 36.3 mg/dL; mean difference -32.2 mg/dL [95% CI -44.5 to -20.0]; P < 0.001) and time above range (61.7 ± 15.1% vs. 73.6 ± 10.4%; mean difference 11.9% [95% CI -16.4 to -7.4]; P < 0.001). HbA1c level was reduced by 0.76% (95% CI -1.1 to -0.4) (-8.5 mmol/mol [95% CI -12.4 to -4.6]; P < 0.001). Times spent below range (<70 mg/dL and <54 mg/dL) were low and comparable during both study periods. Sensor wear was 84% during the CGM period. CONCLUSIONS: CGM use in young people with type 1 diabetes improves time in target and HbA1c levels compared with SMBG.

Glycemic Outcomes of Use of CLC Versus PLGS in Type 1 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: Limited information is available about glycemic outcomes with a closed-loop control (CLC) system compared with a predictive low-glucose suspend (PLGS) system. RESEARCH DESIGN AND METHODS: After 6 months of use of a CLC system in a randomized trial, 109 participants with type 1 diabetes (age range, 14-72 years; mean HbA1c, 7.1% [54 mmol/mol]) were randomly assigned to CLC (N = 54, Control-IQ) or PLGS (N = 55, Basal-IQ) groups for 3 months. The primary outcome was continuous glucose monitor (CGM)-measured time in range (TIR) for 70-180 mg/dL. Baseline CGM metrics were computed from the last 3 months of the preceding study. RESULTS: All 109 participants completed the study. Mean ± SD TIR was 71.1 ± 11.2% at baseline and 67.6 ± 12.6% using intention-to-treat analysis (69.1 ± 12.2% using per-protocol analysis excluding periods of study-wide suspension of device use) over 13 weeks on CLC vs. 70.0 ± 13.6% and 60.4 ± 17.1% on PLGS (difference = 5.9%; 95% CI 3.6%, 8.3%; P < 0.001). Time >180 mg/dL was lower in the CLC group than PLGS group (difference = -6.0%; 95% CI -8.4%, -3.7%; P < 0.001) while time <54 mg/dL was similar (0.04%; 95% CI -0.05%, 0.13%; P = 0.41). HbA1c after 13 weeks was lower on CLC than PLGS (7.2% [55 mmol/mol] vs. 7.5% [56 mmol/mol], difference -0.34% [-3.7 mmol/mol]; 95% CI -0.57% [-6.2 mmol/mol], -0.11% [1.2 mmol/mol]; P = 0.0035). CONCLUSIONS: Following 6 months of CLC, switching to PLGS reduced TIR and increased HbA1c toward their pre-CLC values, while hypoglycemia remained similarly reduced with both CLC and PLGS.

Insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in a case of subcutaneous insulin resistance.

A 38-year-old woman with type 1 diabetes, whose fasting plasma glucose levels were >500 mg/dL under 176 U/day of subcutaneous insulin injection, was admitted to Nippon Medical School Hospital, Tokyo, Japan. When insulin was administered intravenously, she was able to maintain favorable glycemic control even under 24 U/day of regular insulin, showing that she was accompanied by subcutaneous insulin resistance. To choose an optimal insulin regimen, we carried out subcutaneous insulin challenge tests without or with heparin mixture, and found a cocktail of insulin lispro and heparin could reduce blood glucose levels markedly. As a consequence, she achieved favorable blood glucose control by continuous subcutaneous insulin infusion of the cocktail. In summary, the insulin and heparin challenge tests are useful for choosing an optimal insulin regimen in cases of subcutaneous insulin resistance.

Glucose outcomes of a learning-type artificial pancreas with an unannounced meal in type 1 diabetes.

BACKGROUND AND OBJECTIVES: Glycemic control with unannounced meals is the major challenge for artificial pancreas. In this study, we described the performance and safety of learning-type model predictive control (L-MPC) for artificial pancreas challenged by an unannounced meal in type 1 diabetes (T1D). METHODS: This closed-loop (CL) system was tested in 29 T1D patients at one site in a 4 h inpatient open-label study. Participants used an L-MPC CL system for 6 days after 2-day system identification using open-loop (OL) insulin system. During the CL period, the L-MPC system was started from 8:00 am to noon each day. At 9:00 am, each participant consumed 50 g of carbohydrates with no prandial insulin bolus. At 9:30 am on CL-Day 4 or CL-Day 6, participants rode bicycles for 20 minutes or drank 50 ml of beer, in a random order. RESULTS: As the primary outcome, TIR on CL-Day 3 was 65.2±23.3%, which was 9.8 points higher (95% CI 1.8 to 17.8; P = 0.019) than that on CL-Day 1. The time of glucose >10 mmol/L was decreased by 11.0% (95% CI -18.7 to 3.3; P = 0.007), and mean glucose level was decreased by 1.1 mmol/L (95% CI -1.1 to 0.5; P = 0.000). The total daily insulin dosage showed no significant difference (-0.1U, 95% CI -1.34 to 1.32; P = 0.982). Compared with OL-Day1 with a postprandial bolus, the TIR was increased by 13.7 points (95% CI 1.4 to 26.0; P = 0.030), the time of glucose >10 mmol/L and the mean glucose level were also decreased. Compared with the exercise day (CL-Day E, 62.0 ± 23.3%; P = 0.347) or alcohol day (CL-Day A, 64.0 ± 23.6%; P = 0.756), there was no statistically significant difference in terms of TIR, time of glucose >10 mmol/L and mean glucose level. No severe hypoglycemic events occurred and hypoglycemic episodes were not increased by using closed-loop insulin system. CONCLUSION: The L-MPC CL insulin system achieved good glycemic control challenged by an unannounced meal.

Accuracy assessment of bolus and basal rate delivery of different insulin pump systems used in insulin pump therapy of children and adolescents.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is commonly used in patients with diabetes. Accurate and reliable delivery by insulin pumps is essential for a safe and effective therapy, particularly when using small doses. In this study, accuracy of bolus and basal rate delivery of various available insulin pumps was evaluated. METHODS: In total, 13 insulin pump systems were tested: eight durable pumps with different infusion sets and one patch pump. Based on IEC 60601-2-24, insulin delivery was measured by recording weight gain of a beaker into which insulin was infused by the pumps. Bolus accuracy was determined by individually weighing 25 consecutive 0.1 or 1.0 U boluses and basal rate accuracy was determined during basal rate delivery of 0.1 or 1.0 U/h for 72 hours. For analyses, basal rate delivery was divided into 1-hour windows and deviation from target was calculated. RESULTS: Regarding different systems, average 0.1 U bolus delivery was -2% to +9% of the intended volume with 53% to 96% of boluses within ±15% of target. During 0.1 U/h basal rate delivery, most pumps showed an initial over-delivery for the first few hours. Three systems reached a total basal rate error <5%; others showed up to +24%. In general, delivery was more accurate when using larger doses. CONCLUSIONS: Considerable differences in insulin delivery accuracy were observed between the tested pumps. In general, when using very low doses, accuracy of insulin delivery is limited in most insulin pumps. This should be considered for CSII therapy in children.

All Insulin Pumps Are Not Equivalent: A Bench Test Assessment for Several Basal Rates.

Background and Aims: Continuous subcutaneous insulin infusion (CSII) is a widely adopted treatment for type 1 diabetes and is a component of an artificial pancreas. CSII accuracy is essential for glycemic control, however, this metric has not been given sufficient study, especially at the range of the lowest basal rates (BRs), which are commonly used in a pediatric population and in closed-loop systems (CLSs). Our study presents accuracy results of four off-the-shelf CSII systems using a new accurate method for CSII system evaluation. Materials and Methods: The accuracy of four off-the-shelf CSII systems was assessed: Medtronic MiniMed 640G®, Ypsomed YpsoPump®, Insulet Omnipod®, and Tandem t:slim X2®. The assessment was performed using a double-measurement approach through a direct mass flow meter and a time-stamped microgravimetric test bench combined with a Kalman mathematical filter. CSII accuracy was evaluated using mean of dose error. Mean absolute relative difference (MARD) of error was calculated at different observation windows over the whole series of tests. Peakwise insulin deliverance was assessed regarding stroke regularity in terms of frequency and volume. Results: Mean error values indicate a general tendency to underdeliver with up to -16%. MARD of error shows very wide results for each pump and each BR from 7.4% (2 UI/h) to 61.3% (0.1 UI/h). Peakwise analysis shows several choices for BR adaptation (frequency for Omnipod, volume for Tandem, both for YpsoPump and MiniMed 640G). Precision in interstroke time appears to be better (standard deviation [SD] at 0.1 UI/h: 4.6%-12.9%) than stroke volume precision (SD at 0.1 UI/h 38.3%-46.4%). Conclusions: The accuracy of four off-the-shelf CSII systems is model and BR dependent. CSII imprecision could be due to a variability in volume and/or frequency of strokes for every pump. Some models appear better adapted for the smallest insulin needs, or for inclusion in a CLS. The clinical implications of these delivery errors on glucose instability must be evaluated.

HbA1c: The Glucose Management Indicator, Time in Range, and Standardization of Continuous Glucose Monitoring Reports in Clinical Practice.

Continuous glucose monitoring (CGM) use is growing rapidly among people with diabetes and beginning to be standard of care for managing glucose levels in insulin therapy. With this increased use, there is a need to standardize CGM data. CGM standardization has been set forth by expert panels. The Glucose Management Indicator is a concept using the CGM-derived mean glucose to provide a value that can be understood similarly to hemoglobin A1c. The times an individual spends in various glucose ranges is emerging as an important set of metrics. Metrics derived from patient CGM data are changing the way diabetes is managed.

Diabetes Digital App Technology: Benefits, Challenges, and Recommendations. A Consensus Report by the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) Diabetes Technology Working Group.

Digital health technology, especially digital and health applications ("apps"), have been developing rapidly to help people manage their diabetes. Numerous health-related apps provided on smartphones and other wireless devices are available to support people with diabetes who need to adopt either lifestyle interventions or medication adjustments in response to glucose-monitoring data. However, regulations and guidelines have not caught up with the burgeoning field to standardize how mobile health apps are reviewed and monitored for patient safety and clinical validity. The available evidence on the safety and effectiveness of mobile health apps, especially for diabetes, remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore conducted a joint review of the current landscape of available diabetes digital health technology (only stand-alone diabetes apps, as opposed to those that are integral to a regulated medical device, such as insulin pumps, continuous glucose monitoring systems, and automated insulin delivery systems) and practices of regulatory authorities and organizations. We found that, across the U.S. and Europe, mobile apps intended to manage health and wellness are largely unregulated unless they meet the definition of medical devices for therapeutic and/or diagnostic purposes. International organizations, including the International Medical Device Regulators Forum and the World Health Organization, have made strides in classifying different types of digital health technology and integrating digital health technology into the field of medical devices. As the diabetes digital health field continues to develop and become more fully integrated into everyday life, we wish to ensure that it is based on the best evidence for safety and efficacy. As a result, we bring to light several issues that the diabetes community, including regulatory authorities, policy makers, professional organizations, researchers, people with diabetes, and health care professionals, needs to address to ensure that diabetes health technology can meet its full potential. These issues range from inadequate evidence on app accuracy and clinical validity to lack of training provision, poor interoperability and standardization, and insufficient data security. We conclude with a series of recommended actions to resolve some of these shortcomings.