Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).

Sleep duration and association with cardiometabolic health in adolescents and adults with type 1 diabetes: Results from the BCQR-T1D study.

AIM: Type 1 diabetes (T1D) increases the risk of morbidity and mortality from cardiovascular disease, and insufficient sleep is prevalent. Emerging evidence suggests a link between sleep and cardiometabolic health, but this has not been examined across the lifespan in individuals with T1D. We aimed to examine associations between sleep and cardiometabolic health in adolescents and adults with T1D in a secondary analysis of data from a 4-week double-blind, random-order, placebo-controlled crossover trial of bromocriptine quick release (BCQR) therapy with a 4-week washout in between conditions. MATERIALS AND METHODS: Forty-two adults (19-60 years) and 42 adolescents (12-18 years) with T1D >9 months completed 1 week of home monitoring with wrist-worn actigraphy to estimate sleep duration and continuous glucose monitoring, anthropometrics, arterial stiffness, magnetic resonance imaging (adolescents only), and fasting laboratory testing at each treatment phase. RESULTS: Sixty-two per cent of adolescents and 74% of adults obtained <7 h of sleep per night at baseline. After adjustment for age, sex and diabetes duration, baseline sleep <7 h per night was associated with a higher body mass index, a higher waist circumference, a higher systolic blood pressure, worse arterial stiffness and a lower estimated insulin sensitivity (all p < .05). When examined by age group, associations between sleep duration and cardiometabolic health outcomes remained significant, predominantly for adolescents. In adolescents only, wake time was significantly later (p = .027) and time in bed was significantly longer with BCQR versus placebo (p = .049). CONCLUSIONS: Objectively measured sleep <7 h per night was prevalent in adolescents and adults with T1D and associated with poorer cardiometabolic health markers. Small changes in sleep were seen following BCQR treatment in adolescents only. Sleep may be an important and novel target for improving cardiometabolic health in individuals with T1D.

Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes.

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).

Increasing Use of Diabetes Devices: What Do Health Care Professionals Need?

Despite evidence of improved diabetes outcomes with diabetes technology such as continuous glucose monitoring (CGM) systems, insulin pumps, and hybrid closed-loop (HCL) insulin delivery systems, these devices are underutilized in clinical practice for the management of insulin-requiring diabetes. This low uptake may be the result of health care providers' (HCPs') lack of confidence or time to prescribe and manage devices for people with diabetes. We administered a survey to HCPs in primary care, pediatric endocrinology, and adult endocrinology practices in the United States. Responding HCPs expressed a need for device-related insurance coverage tools and online data platforms with integration to electronic health record systems to improve diabetes technology uptake in these practice settings across the United States.

Bromocriptine quick-release as adjunct therapy in youth and adults with type 1 diabetes: A randomized, placebo-controlled crossover study.

AIM: To evaluate the potential for glycaemic, renal and vascular benefits of bromocriptine quick release (BCQR) in adolescents and adults with type 1 diabetes. MATERIALS AND METHODS: Forty adolescents and 40 adults with type 1 diabetes aged 12-60 years old were enrolled in a double-blind, placebo-controlled, random order crossover study of 4 weeks of treatment in the morning with BCQR (titrated weekly from 0.8 mg to 1.6 mg to 3.2 mg, minimum dose 1.6 mg). Study assessments after each phase included blood pressure (BP), lipids, peripheral arterial stiffness and autonomic function, mixed meal tolerance test, continuous glucose monitoring (CGM), creatinine, estimated glomerular filtration rate, estimated insulin sensitivity, insulin dose and indirect calorimetry. RESULTS: Adolescents displayed baseline hyperglycaemia, insulin resistance, metabolic dysfunction and increased renal filtration compared with adults. In both age groups, continuous glucose monitoring measures, estimated insulin sensitivity and insulin dose did not differ with BCQR treatment. In adolescents, BCQR decreased systolic BP, diastolic BP and triangular index and increased serum creatinine. In adults, systolic BP, mean arterial pressure, systemic vascular resistance, and mixed meal tolerance test glucose and glucagon-like peptide 1 areas under the curve were lower, and the orthostatic drop in systolic BP was greater with BCQR. CONCLUSIONS: Greater hyperglycaemia, insulin resistance, metabolic dysfunction and renal hyperfiltration in adolescents argues for increased attention during this high-risk age period. Although BCQR had little impact on glycaemia or insulin sensitivity, initial vascular and renal responses suggest potential benefits of BCQR in adolescents and adults with type 1 diabetes requiring further study.

Factors Associated With Improved A1C Among Adults With Type 1 Diabetes in the United States.

Many adults with diabetes do not reach optimal glycemic targets, and, despite advances in diabetes management, diabetes technology use remains significantly lower in racial/ethnic minority groups. This study aimed to identify factors associated with achieving the recommended A1C target of <7% using data on 12,035 adults with type 1 diabetes from 15 centers participating in the T1D Exchange Quality Improvement Collaborative. Individuals attaining the target A1C were more likely to be older, White, have private health insurance, and use diabetes technology and less likely to report depressive symptoms or episodes of severe hypoglycemia or diabetic ketoacidosis than those with higher A1C levels. These findings highlight the importance of overcoming inequities in diabetes care.

Inequities in Health Outcomes in Children and Adults With Type 1 Diabetes: Data From the T1D Exchange Quality Improvement Collaborative.

Health care inequities among racial and ethnic groups remain prevalent. For people with type 1 diabetes who require increased medical access and care, disparities are seen in access to care and health outcomes. This article reports on a study by the T1D Exchange Quality Improvement Collaborative evaluating differences in A1C, diabetic ketoacidosis (DKA), severe hypoglycemia, and technology use among racial and ethnic groups. In a diverse cohort of nearly 20,000 children and adults with type 1 diabetes, A1C was found to differ significantly among racial and ethnic groups. Non-Hispanic Blacks had higher rates of DKA and severe hypoglycemia and the lowest rate of technology use. These results underscore the crucial need to study and overcome the barriers that lead to inequities in the care and outcomes of people with type 1 diabetes.

Case series of a hybrid closed-loop system used in pregnancies in clinical practice.

BACKGROUND: Hybrid closed-loop (HCL) therapy is rarely studied in pregnancy. We present three cases of women with type 1 diabetes who used the Medtronic 670G HCL system for most or all of gestation. METHODS: The Medtronic 670G system has a manual mode (no automated insulin delivery) and an auto mode (AM, HCL therapy). Women in this case series used AM off-label in gestation. RESULTS: Case 1 started HCL therapy in the second trimester, her sensor glucose time spent <3.9 and >10 mmol/L improved thereafter. Case 1 had average sensor glucose (ASG) levels of 6.4 ± 2.4 mmol/L in the first trimester, 7.0 ± 2.7 mmol/L in the second trimester before HCL use, 7.1 ± 2.1 mmol/L in the second trimester after HCL use, and 6.8 ± 1.9 mmol/L in the third trimester. Case 1 continued AM during operative delivery and post-partum. Cases 2 and 3 used HCL therapy throughout gestation but with inconsistent time in AM. When they increased time in AM their glycaemic indices improved. Case 2 had ASG of 9.5 ± 3.4, 8.6 ± 2.9, and 7.9 ± 2.5 mmol/L in the first through third trimesters, respectively. Case 3 had ASG of 11.1 ± 4.8 and 3.9 to 10 mmol/L in the first and second trimesters, respectively. Case 2 continued HCL therapy post-partum, Case 3 did not. CONCLUSIONS: CareLink® Clinical Software only reports the non-pregnant time in range. Nonetheless, this represents the first report of HCL therapy in pregnancy with a system approved by the Food and Drug Administration in non-pregnant populations.

Alcohol Consumption, Diabetes Risk, and Cardiovascular Disease Within Diabetes.

PURPOSE OF REVIEW: The purpose of the study is to examine and summarize studies reporting on the epidemiology, the risk of developing diabetes, and the cardiovascular effects on individuals with diabetes of different levels of alcohol consumption. RECENT FINDINGS: Men consume more alcohol than women in populations with and without diabetes. Light-to-moderate alcohol consumption decreases the incidence of diabetes in the majority of the studies, whereas heavy drinkers and binge drinkers are at increased risk for diabetes. Among people with diabetes, light-to-moderate alcohol consumption reduces risks of cardiovascular diseases and all-cause mortality. Alcohol consumption is less common among populations with diabetes compared to the general population. Moderate alcohol consumption reduces the risk of diabetes and, as in the general population, improves cardiovascular health in patients with diabetes. Type of alcoholic beverage, gender, and body mass index are factors that affect these outcomes.

The influence of herbs and spices on overall liking of reduced fat food.

Most adults consume more fat than is recommended in the Dietary Guidelines for Americans. We examined whether adding herbs and spices to reduced-fat foods would improve their consumer liking. We recruited adults 18-65 years old to taste three lunch conditions: full fat (FF), reduced fat with no added spice (RF), and reduced fat plus spice (RFS). Subjects rated their liking of a meatloaf entrée, vegetable side dish, pasta side dish, and overall meal on a 9-point hedonic Likert scale. Subjects came weekly for 3 weeks to consume meals and were randomized to the condition order. We enrolled 148 subjects who were predominantly female (n = 101, 68%), had a mean age of 35.9 years, and body mass index of 24.4 kg/m2. Subjects reported habitual diets as 36% of total calories from fat (2005 Block Food Frequency Questionnaire). Reducing fat content alone significantly dropped overall liking of the meal compared with FF and RFS conditions (6.29 RF vs. 7.05 FF, P < 0.0001; 6.29 RF vs. 6.98 RFS, P ≤ 0.0001). The RFS overall meal was liked as well as the FF condition. FF and RFS conditions were liked significantly more than RF conditions for each meal item. Liking of FF and RFS meatloaf and vegetables were not significantly different from one another. Pasta FF and RFS conditions were rated significantly differently from each other (7.33 FF vs. 6.61 RFS, P < 0.0001). Adding herbs and spices to reduced fat foods restored liking of the overall meal, meatloaf, and vegetables to that of FF conditions, and significantly improved the liking of RF pasta. Herbs and spices can be a useful tool to improve liking of foods consistent with national guidelines.

Clinical Effectiveness of Continuous Glucose Monitoring in Pregnancies Affected by Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) improves neonatal outcomes in type 1 diabetes pregnancies; however, its effectiveness has not been assessed in a real-world setting in the United States. Objective: The Triple C Study aimed to examine the clinical effectiveness, assessed through maternal glucose control and gestational health outcomes, of CGM use compared with self-monitoring of blood glucose (SMBG) in pregnancies associated with type 1 diabetes in a real-world setting. Research Design and Methods: We retrospectively identified 160 type 1 diabetes pregnancies at the Barbara Davis Center for Diabetes managed with CGM therapy (n = 109) or SMBG (n = 51) over a 6.5-year period (2014-2020). Obstetric care was provided at multiple practices. CGM use was defined as ≥60% wear in the second and third trimesters of pregnancy. Data were obtained from the electronic medical record system, hospital records, and vital statistics departments (Colorado and Wyoming). We used Student's t-test for continuous variables and chi-square test for categorical variables to compare outcomes between groups. Results: The CGM group had more participants meeting trimester-specific hemoglobin A1C (HbA1c) goals throughout pregnancy and postpartum (P < 0.01 in each time period). The CGM group had fewer participants never meeting HbA1c goals in any trimester than the SMBG group (P < 0.001). There were no significant differences in neonatal outcomes between groups, other than for macrosomia (12.8% CGM vs. 29.4% SMBG, P = 0.01). Infants of CGM users required a neonatal intensive care unit admission less often (52.9% CGM vs. 68.3% SMBG, P = 0.0989). Conclusions: CGM use was associated with improved maternal glucose levels in a diverse real-world cohort.

Continuous Glucose Monitoring Metrics for Pregnancies Complicated by Diabetes: Critical Appraisal of Current Evidence.

Ascertaining the utility of continuous glucose monitoring (CGM) in pregnancy complicated by diabetes is a rapidly evolving area, as the prevalence of type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) escalates. The seminal randomized controlled trial (RCT) evaluating CGM use added to standard care in pregnancy in T1D demonstrated significant improvements in maternal glycemia and neonatal health outcomes. Current clinical guidance recommends targets for percentage time in range (TIR), time above range (TAR), and time below range (TBR) during pregnancy complicated by T1D that are widely used in clinical practice. However, the superiority of CGM over blood glucose monitoring (BGM) is still questioned in both T2D and GDM, and whether glucose targets should be different than in T1D is unknown. Questions requiring additional research include which CGM metrics are superior in predicting clinical outcomes, how should pregnancy-specific CGM targets be defined, whether CGM targets should differ according to gestational age, and if CGM metrics during pregnancy should be similar across all types of diabetes. Limiting the potential for CGM to improve pregnancy outcomes may be our inability to maintain TIR > 70% throughout gestation, a goal achieved in the minority of patients studied. Adverse pregnancy outcomes remain high in women with T1D and T2D in pregnancy despite CGM technology, and this review explores the potential reasons and questions yet to be investigated.

Time in Range Is Associated with Incident Diabetic Retinopathy in Adults with Type 1 Diabetes: A Longitudinal Study.

Abstract Objective: To evaluate the association between continuous glucose monitoring (CGM)-based time in various ranges and the subsequent development of diabetic retinopathy (incident DR) in adults with type 1 diabetes. Methods: Between June 2018 and March 2022, adults with type 1 diabetes with incident DR or no retinopathy (control) were identified. CGM data were collected retrospectively for up to 7 years before the date of eye examination defining incident DR or control. Associations between incident DR and CGM metrics were evaluated using logistic regression models. Results: This analysis included 71 adults with incident DR (mean age 27 years, 52% females, and mean diabetes duration 15 years) and 92 adults without DR (mean age 38 years, 48% females, and mean diabetes duration 20 years). Adjusting for age, diabetes duration, and CGM type, each 0.5% increase in glycated hemoglobin (HbA1c), 10 mg/dL increase in mean glucose, 5% decrease in time in target range 70-180 mg/dL (TIR), 5% decrease in time in tight target range 70-140 mg/dL (TITR), and 5% increase in time above 180 mg/dL (TAR) were associated with 24%, 22%, 18%, 28%, and 20% increase in odds of incident DR, respectively. Spearman correlations of TIR, TITR, TAR, and mean glucose with each other were all ≥0.97. Conclusion: Similar to HbA1c, TIR, TITR, TAR, and mean glucose were associated with increased risk for incident DR in adults with type 1 diabetes. These CGM metrics are highly correlated indicating that they provide similar information on glycemic control and diabetic retinopathy risk.

Randomized Trial of Assisted Hybrid Closed-Loop Therapy Versus Sensor-Augmented Pump Therapy in Pregnancy.

Objective: Examine gestational safety, glycemic and health outcomes, of a hybrid closed-loop (HCL) system without pregnancy-specific glucose targets. Research Design: This was a pilot feasibility investigator-initiated, two-site, single-blind, randomized controlled trial of sensor-augmented pump therapy (SAPT) versus HCL therapy in type 1 diabetes pregnancies. Participants were enrolled in the first trimester and randomized at 14-18 weeks of gestation and used SAPT or HCL until 4-6 weeks postpartum. We compared continuous glucose monitoring (CGM) metrics, severe hypoglycemia (SH), diabetic ketoacidosis (DKA), adverse skin reactions, and pregnancy outcomes between groups. Results: Baseline characteristics were similar between groups (n = 11 HCL and n = 12 SAPT). There was no SH or DKA episode after randomization. Time spent <54 mg/dL did not differ between groups. Time spent <63 mg/dL decreased in both groups, significantly in the HCL group (3.5% [1.3% standard error] second trimester and 2.8% [1.3%] third trimester vs. 7.9% [1.3%] run-in phase, P < 0.05 for both). Mean sensor glucose was lower with SAPT compared to HCL therapy in the third trimester (119 [4] mg/dL SAPT vs. 132 [4] mg/dL HCL, P < 0.05). Third trimester time-in-range (TIR; 63-140 mg/dL) increased with SAPT (68.2% [3.1%] vs. 64.3% [3.1%] run-in phase, P < 0.05). Gestational health outcomes did not differ between groups. The HCL group used assistive techniques, such as fake carbohydrate boluses and exiting HCL overnight. Conclusions: CGM within group differences were seen for time <63 mg/dL favoring HCL therapy and TIR favoring SAPT (third trimester vs. baseline). Safety and adverse pregnancy outcomes were similar between groups.

Performance of the Dexcom G7 Continuous Glucose Monitoring System in Pregnant Women with Diabetes.

Background: We evaluated accuracy and safety of a seventh-generation real-time continuous glucose monitoring (CGM) system during pregnancy. Materials and Methods: Evaluable data for accuracy analysis were obtained from 96 G7 sensors (Dexcom, Inc.) worn by 96 of 105 enrolled pregnant women with type 1 (n = 59), type 2 (n = 21), or gestational diabetes (n = 25). CGM values were compared with arterialized venous glucose values from the YSI comparator instrument during 6-h clinic sessions at different time points throughout the sensors' 10-day wear period. The primary endpoint was the proportion of CGM values in the 70-180 mg/dL range within 15% of comparator glucose values. Secondary endpoints included the proportion of CGM values within 20% or 20 mg/dL of comparator values ≥ or <100 mg/dL, respectively (the %20/20 agreement rate). Results: Of the 1739 pairs with CGM in the 70-180 mg/dL range, 83.2% were within 15% of comparator values. The lower bound of the 95% confidence interval was 79.8%. Of the 2102 pairs with CGM values in the 40-400 mg/dL range, the %20/20 agreement rate was 92.5%. Of the 1659 pairs with comparator values in the 63-140 mg/dL range, the %20/20 agreement rate was 92.3%. The %20/20 agreement rates on days 1, 4 and 7, and 10 were 78.6%, 96.3%, and 97.3%, respectively. Consensus error grid analysis showed 99.8% of pairs in the clinically acceptable A and B zones. There were no serious adverse events. The sensors' 10-day survival rate was 90.3%. Conclusion: The G7 system is accurate and safe during pregnancies complicated by diabetes and does not require confirmatory fingerstick testing. Clinical Trial Registration: clinicaltrials.gov NCT04905628.

Expert Guidance on Off-Label Use of Hybrid Closed-Loop Therapy in Pregnancies Complicated by Diabetes.

Automated insulin delivery (AID) systems have established benefits in terms of glycemic control, health outcomes, and quality of life and are strongly recommended for people with type 1 diabetes outside of pregnancy. While evidence for use of investigational AID systems during pregnancy is promising, data and guidance are still needed regarding use of commercially available systems during pregnancy. Unfortunately, none of the hybrid closed-loop (HCL) systems that are currently available in the United States have glucose targets that are as aggressive as pregnancy glycemic targets, none have a pregnancy-specific algorithm, and none are approved for use during pregnancy. As such, any use of these systems during pregnancy is considered off-label in the United States and would be "assisted" by provider/user techniques. Despite these limitations, many women conceive while using clinically available HCL systems and may be hesitant to cease use during pregnancy. Achievement of strict pregnancy glycemic targets can be difficult, and it is conceivable that selective off-label use of clinically available HCL systems in some women could lead to improved glycemia. We herein offer expert guidance based on clinical experience and available case reports on how to identify appropriate candidates for HCL therapy in pregnancy, how to counsel pregnant women with diabetes on the potential risks and benefits of HCL therapy during pregnancy, and how to manage commercially available systems off-label throughout gestation in an assisted HCL approach.