Evaluating HbA1c-to-average glucose conversion with patient-specific kinetic models for diverse populations.

The discrepancy between estimated glycemia from HbA1c values and actual average glucose (AG) levels has significant implications for treatment decisions and patient understanding. Factors contributing to the gap include red blood cell (RBC) lifespan and glucose uptake into the RBC. Personalized models have been proposed to enhance AG prediction accuracy by considering interpersonal variation. This study contributes to our understanding of personalized models for estimating AG from HbA1c. Utilizing data from seven studies (340 participants), including Hispanic/Latino populations with or at risk of non-insulin-treated type 2 diabetes (T2D), we examined kinetic features across cohorts. Additionally, the study simulated scenarios to understand data requirements for improving accuracy. Personalized approaches improved agreement between AG estimations and CGM-AG, particularly with four or more weeks of training CGM data. A multiple linear regression model using kinetic parameters and added clinical features was shown to improve the accuracy of personalized models further. As CGM usage extends beyond type 1 diabetes, there is growing interest in leveraging CGM data for clinical decision-making. Patient-specific models offer a valuable tool for managing glycemic status in patients with discordant HbA1c and AG values.

A probabilistic computation framework to estimate the dawn phenomenon in type 2 diabetes using continuous glucose monitoring.

In type 2 diabetes (T2D), the dawn phenomenon is an overnight glucose rise recognized to contribute to overall glycemia and is a potential target for therapeutic intervention. Existing CGM-based approaches do not account for sensor error, which can mask the true extent of the dawn phenomenon. To address this challenge, we developed a probabilistic framework that incorporates sensor error to assign a probability to the occurrence of dawn phenomenon. In contrast, the current approaches label glucose fluctuations as dawn phenomena as a binary yes/no. We compared the proposed probabilistic model with a standard binary model on CGM data from 173 participants (71% female, 87% Hispanic/Latino, 54 ± 12 years, with either a diagnosis of T2D for six months or with an elevated risk of T2D) stratified by HbA1c levels into normal but at risk for T2D, with pre-T2D, or with non-insulin-treated T2D. The probabilistic model revealed a higher dawn phenomenon frequency in T2D [49% (95% CI 37-63%)] compared to pre-T2D [36% (95% CI 31-48%), p = 0.01] and at-risk participants [34% (95% CI 27-39%), p < 0.0001]. While these trends were also found using the binary approach, the probabilistic model identified significantly greater dawn phenomenon frequency than the traditional binary model across all three HbA1c sub-groups (p < 0.0001), indicating its potential to detect the dawn phenomenon earlier across diabetes risk categories.

Multimodal digital phenotyping of diet, physical activity, and glycemia in Hispanic/Latino adults with or at risk of type 2 diabetes.

Digital phenotyping refers to characterizing human bio-behavior through wearables, personal devices, and digital health technologies. Digital phenotyping in populations facing a disproportionate burden of type 2 diabetes (T2D) and health disparities continues to lag compared to other populations. Here, we report our study demonstrating the application of multimodal digital phenotyping, i.e., the simultaneous use of CGM, physical activity monitors, and meal tracking in Hispanic/Latino individuals with or at risk of T2D. For 14 days, 36 Hispanic/Latino adults (28 female, 14 with non-insulin treated T2D) wore a continuous glucose monitor (CGM) and a physical activity monitor (Actigraph) while simultaneously logging meals using the MyFitnessPal app. We model meal events and daily digital biomarkers representing diet, physical activity choices, and corresponding glycemic response. We develop a digital biomarker for meal events that differentiates meal events into normal and elevated categories. We examine the contribution of daily digital biomarkers of elevated meal event count and step count on daily time-in-range 54-140 mg/dL (TIR54-140) and average glucose. After adjusting for step count, a change in elevated meal event count from zero to two decreases TIR54-140 by 4.0% (p = 0.003). An increase in 1000 steps in post-meal step count also reduces the meal event glucose response by 641 min mg/dL (p = 0.0006) and reduces the odds of an elevated meal event by 55% (p < 0.0001). The proposed meal event digital biomarkers may provide an opportunity for non-pharmacologic interventions for Hispanic/Latino adults facing a disproportionate burden of T2D.

Temporal changes in bio-behavioral and glycemic outcomes following a produce prescription program among predominantly Hispanic/Latino adults with or at risk of type 2 diabetes.

In the United States (U.S.), consumption of fresh vegetables and fruits is below recommended levels. Enhancing access to nutritious food through food prescriptions has been recognized as a promising approach to combat diet-related illnesses. However, the effectiveness of this strategy at a large scale remains untested, particularly in marginalized communities where food insecurity rates and the prevalence of health conditions such as type 2 diabetes (T2D) are higher compared to the background population. This study evaluated the impact of a produce prescription program for predominantly Hispanic/Latino adults living with or at risk of T2D. A total of 303 participants enrolled in a 3-month observational cohort received 21 medically prescribed portions/week of fresh produce. A subgroup of 189 participants used continuous glucose monitoring (CGM) to assess the relationship between CGM profile changes and HbA1c level changes. For 247 participants completing the study (76% female, 84% Hispanic/Latino, 32% with T2D, age 56·6 ± 11·9 years), there was a reduction in weight (-1·1 [-1·6 to -0·6] lbs., p < 0.001), waist circumference (-0·4 [-1·0 to 0·6] cm, p = 0·007) and systolic blood pressure (SBP) for participants with baseline SBP >120 mmHg (-4·2 [-6·8 to -1·8] mmHg, p = 0·001). For participants with an HbA1c ≥ 7·0% at baseline, HbA1c fell significantly (-0·5 [-0·9 to -0·1] %, p = 0·01). There were also improvements in food security (p < 0·0001), self-reported ratings of sleep, mood, pain (all p < 0·001), and measures of depression (p < 0·0001), anxiety (p = 0·045), and stress (p = 0·002) (DASS-21). There was significant correlation (r = 0·8, p = 0·001) between HbA1c change and the change in average glucose for participants with worsening HbA1c, but not for participants with an improvement in HbA1c. In conclusion, medical prescription of fresh produce is associated with significant improvements in cardio-metabolic and psycho-social risk factors for Hispanic/Latino adults with or at risk of T2D.

Patterns of Timing and Intensity of Physical Activity and HbA1c Levels in Hispanic/Latino Adults With or at Risk of Type 2 Diabetes.

Despite the clear benefits of increased physical activity (PA) on glycemic control, little is known about the importance of the timing of exercise among people with diabetes. Our objective was to compare the time of day of PA with concurrent HbA1c levels and body mass index (BMI) among Hispanic/Latino adults with or at risk of type 2 diabetes (T2D).Monitored activity data obtained from Hispanic/Latino adults were summarized as number of steps per day, moderate-to-vigorous-intensity physical activity (MVPA), and energy expenditure (kcals/day). We next examined the association between PA measures and participants' HbA1c. K-means clustering analysis was applied to identify daily PA patterns by time of day and intensity. Thus, three dominant clusters were identified: low-intensity PA, and early and late PA by time of day.The step counts were correlated with HbA1c in the late-active group (P = .01). Furthermore, independently in younger adults (age ≤ 50 years) and in overweight adults (25 ≤ BMI < 30 kg/m2), there was an association between HbA1c and step counts (P < .01 and P < .005, respectively) as well as HbA1c and MVPA (P < .05 and P < .035, respectively).In conclusion, for Hispanic/Latino adults with or at risk of T2D, there appears to be clustering of PA by intensity and time of day which, in turn, may influence achieved HbA1c and BMI. Our findings demonstrate that the amount of activity is more efficacious on HbA1c in participants who are more active later during the day and separately in overweight and younger individuals.This finding may help design more personalized PA recommendations in this population.ClinicalTrials.gov Identifiers: NCT03830840 and NCT03736468.

The northeast glucose drift: Stratification of post-breakfast dysglycemia among predominantly Hispanic/Latino adults at-risk or with type 2 diabetes.

Background: There is minimal experience in continuous glucose monitoring (CGM) among underserved racial/ethnic minority populations with or at risk of type 2 diabetes (T2D), and therefore a lack of CGM-driven insight for these individuals. We analyzed breakfast-related CGM profiles of free-living, predominantly Hispanic/Latino individuals at-risk of T2D, with pre-T2D, or with non-insulin treated T2D. Methods: Starting February 2019, 119 participants in Santa Barbara, CA, USA, (93 female, 87% Hispanic/Latino [predominantly Mexican-American], age 54·4 [±12·1] years), stratified by HbA1c levels into (i) at-risk of T2D, (ii) with pre-T2D, and (iii) with non-insulin treated T2D, wore blinded CGMs for two weeks. We compared valid CGM profiles from 106 of these participants representing glucose response to breakfast using four parameters. Findings: A "northeast drift" was observed in breakfast glucose responses comparing at-risk to pre-T2D to T2D participants. T2D participants had a significantly higher pre-breakfast glucose level, glucose rise, glucose incremental area under the curve (all p < 0·0001), and time to glucose peak (p < 0·05) compared to pre-T2D and at-risk participants. After adjusting for demographic and clinical covariates, pre-breakfast glucose and time to peak (p < 0·0001) were significantly associated with HbA1c. The model predicted HbA1c within (0·55 ± 0·67)% of true laboratory HbA1c values. Interpretation: For predominantly Hispanic/Latino adults, the average two-week breakfast glucose response shows a progression of dysglycemia from at-risk of T2D to pre-T2D to T2D. CGM-based breakfast metrics have the potential to predict HbA1c levels and monitor diabetes progression. Funding: US Department of Agriculture (Grant #2018-33800-28404), a seed grant from the industry board fees of the NSF Engineering Research Center for Precise Advanced Technologies and Health Systems for Underserved Populations (PATHS-UP) (Award #1648451), and the Elsevier foundation.

Traveling Across Time Zones With Type 1 Diabetes: A Pilot Study Comparing Insulin Degludec With Insulin Glargine U100.

OBJECTIVE: For people with type 1 diabetes, there are limited evidence-based resources to support self-management when traveling across multiple time zones. Here, we compared glycemic control on insulin degludec versus glargine U100 as the basal insulin for adults using multiple daily injections (MDI) while traveling across multiple time zones. RESEARCH DESIGN AND METHODS: This randomized crossover pilot study compared insulin degludec versus glargine U100 for adults with type 1 diabetes using MDI insulin during long-haul travel to and from Hawaii to New York. Insulin degludec was administered daily at the same time regardless of time zone, and glargine was administered per travel algorithm. Primary end point was the percentage of time in range (TIR) between 70 and 140 mg/dL during the initial 24 h after each direction of travel. Secondary end points included standard continuous glucose monitoring metrics, jet lag, fatigue, and sleep. RESULTS: The study enrolled 25 participants (56% women, mean ± SD age of 35 ± 14.5 years, HbA1c of 7.4 ± 1.2% [57 ± 13.1 mmol/mol], and diabetes duration of 20.6 ± 15 years). There was no significant difference in glycemic outcomes between the two arms of the study, including TIR, hypoglycemia, or hyperglycemia. Neither group achieved >70% TIR 70-180 mg/dL during travel. Jet lag was greater on glargine U100 in eastward travel but not westward. Fatigue was greater after westward travel on glargine. Sleep was not significantly different between basal insulins. CONCLUSIONS: In adults with type 1 diabetes using MDI of insulin and traveling across multiple time zones, glycemic outcomes were similar comparing insulin degludec and glargine U100.

Dysglycemia in adults at risk for or living with non-insulin treated type 2 diabetes: Insights from continuous glucose monitoring.

BACKGROUND: Continuous glucose monitoring (CGM) has demonstrable benefits for people living with diabetes, but the supporting evidence is almost exclusively from White individuals with type 1 diabetes. Here, we have quantified CGM profiles in Hispanic/Latino adults with or at-risk of non-insulin treated type 2 diabetes (T2D). METHODS: 100 participants (79 female, 86% Hispanic/Latino [predominantly Mexican], age 54·6 [±12·0] years) stratified into (i) at risk of T2D, (ii) with pre-diabetes (pre-T2D), and (iii) with non-insulin treated T2D, wore blinded CGMs for 2 weeks. Beyond standardized CGM measures (average glucose, glucose variability, time in 70-140 mg/dL and 70-180 mg/dL ranges), we also examined additional CGM measures based on the time of day. FINDINGS: Standardized CGM measures were significantly different for participants with T2D compared to at-risk and pre-T2D participants (p<0·0001). In addition, pre-T2D participants spent more time between 140 and 180 mg/dL during the day than at-risk participants (p<0·01). T2D participants spent more time between 140 and 180 mg/dL both during the day and overnight compared to at-risk and pre-T2D participants (both p<0·0001). Time in 70-140 mg/dL range during the day was significantly correlated with HbA1c (r=-0·72, p<0·0001), after adjusting for age, sex, BMI, and waist circumference (p<0·0001). INTERPRETATION: Standardized CGM measures show a progression of dysglycemia from at-risk of T2D, to pre-T2D, and to T2D. Stratifying CGM readings by time of day and the range 140-180 mg/dL provides additional metrics to differentiate between the groups. FUNDING: US Department of Agriculture (Grant #2018-33800-28404) and NSF PATHS-UP ERC (Award #1648451).

Insurance Status and Biological and Psychosocial Determinants of Cardiometabolic Risk Among Mexican-Origin U.S. Hispanic/Latino Adults with Type 2 Diabetes.

Purpose: Hispanics/Latinos in the United States bear higher burden of type 2 diabetes (T2D) and associated complications compared with the general population. Health insurance coverage is also lower in this population. We examined the association of health insurance with biological and psychosocial determinants of cardiometabolic risk among U.S. Mexican-origin Hispanic/Latino adults with T2D. Methods: Participants were self-reported Hispanic/Latino adults with T2D diagnosis. Trained bilingual community health workers collected cross-sectional information on biological and psychosocial factors using clinical examinations, laboratory tests, validated questionnaires, and wearable activity monitors. Results: One hundred and seven Hispanic/Latino adults (54±12 years, 65% female, 36% prescribed insulin, 60% uninsured) with T2D were enrolled. While 93% had low language-based acculturation, 88% had high health literacy in Spanish. Forty percent were food insecure and 47% expressed at least one social need. Overall, 35% had an HbA1c <7.0% (indicating good control) and 31% had an HbA1c >9.0%. Sixty-three percent had blood pressure within target (<130/80 mmHg), and overall participants were moderately physically active. However, 53% were obese (body mass index ≥30 kg/m2) and 76% had a waist measurement defined as high risk (>88 cm for women and >102 cm for men). Participants without health insurance were younger (51.9±10.4 vs. 58.8±10.5 years mean±standard deviation, p=0.0008) but had higher HbA1c (8.4±2.2% vs. 7.6±1.6, p=0.031) and fasting glucose (184.9±86.5 vs. 148.6±61.2 mg/dl, p=0.008) levels. Conclusions: Health insurance status appears to influence achieved glycemic control for U.S. Hispanic/Latino adults with T2D. However, various psychosocial factors potentially influencing cardiometabolic risk independently of health insurance status may also be implicated in the inequitable burden of T2D. ClinicalTrials.gov Identifier: NCT03736486.

Self-reported and objectively measured physical activity levels among Hispanic/Latino adults with type 2 diabetes.

OBJECTIVE: In the USA, minority populations face a disproportionate burden from type 2 diabetes (T2D), in whom physical activity (PA) is recommended. The aim of this study was to determine levels of PA among a community of free-living Hispanic/Latino adults with T2D using a research accelerometer, a consumer device and a pictogram self-assessment questionnaire. RESEARCH DESIGN AND METHODS: This was a cross-sectional, observational study. Participants (57 women and 31 men, body mass index (kg/m2) 32.2±7.9 and 29.9±4.5, waist circumference 97.1±30.1 and 93.7±33.0 cm and hemoglobin A1c 8.0±2.0 and 8.1%±1.8%, respectively) wore an ActiGraph (AG) on the hip and a Fitbit (FB) on the wrist for 1 week to estimate daily steps and energy expenditure (EE). Participants reported type and intensity of PA using English-language or Spanish-language pictograms and a 10-point Likert scale (1='not active' to 10='very, very active'). RESULTS: Steps per day were not normally distributed; AG median steps/weekday (Monday-Friday) was 6990 (range 1091-25 884) compared with 9329 (288-31 669) using FB (p≤0.01). Both devices recorded significantly more steps on weekdays versus weekends (p≤0.05). EE was also higher during the week. AG and FB were highly correlated to each other (p<0.01). Men were more active than women and maintained their PA throughout the week, whereas women decreased theirs on weekends. Spanish-language pictograms were preferred and self-reported PA matched objective assessments by both devices. Participants perceived themselves to be active (7.1±2.0) due to work. CONCLUSIONS: Both objectively measured and self-reported levels of PA in Hispanic/Latino adults with T2D challenge the assumption that lack of PA may be commonplace for this group. AG and FB are different in their measurement of PA but are significantly correlated. New strategies, including use of pictograms, for interventions need to be considered if further increases or changes in PA are to be used as T2D therapy. TRIAL REGISTRATION NUMBER: NCT03736486.

Real-World Association of Insurance Status with Cardio-metabolic Risk for Hispanic/Latino Adults Living on the Central Coast of California.

The primary aim of this study was to evaluate cardio-metabolic burden by insurance status for Hispanic/Latino adults in Santa Barbara, CA. HbA1c, body mass index (BMI), and health insurance status were evaluated via community-based screenings. Cardiovascular (CV) risk was assessed using the Framingham Heart Study calculator and compared with a National Health and Nutrition Examination Survey background population. Of 593 participants (73% female, age 47.3 years (SD ± 15.2), 44.5% had no insurance or did not know if they had insurance. 16% had an HbA1c in the diabetes range, comprised of 9% self-reporting diabetes and 7% self-reporting no diabetes. 39% had an HbA1c in the prediabetes range. Elevated HbA1c was associated with significantly higher BMI (p = 0.003) and lack of health insurance (p = 0.031). 10-year CV risk was significantly higher than the general population (p < 0.001). This program identified a high burden of cardio-metabolic disease and uninsurance coverage in Hispanic/Latino adults in Santa Barbara.

Understanding the impact of five major determinants of health (genetics, biology, behavior, psychology, society/environment) on type 2 diabetes in U.S. Hispanic/Latino families: Mil Familias - a cohort study.

BACKGROUND: In the United States (U.S.), the prevalence of both diagnosed and undiagnosed type 2 diabetes (T2D) is nearly twice as high among Mexican-origin Hispanic/Latino adults compared to non-Hispanic Whites. Rates of diabetes-related complications, e.g., acute stroke and end-stage renal disease, are also higher among Hispanic/Latino adults compared to their non-Hispanic/Latino White counterparts. Beyond genetic and biological factors, it is now recognized that sociocultural influences are also important factors in determining risk for T2D and the associated complications. These influences include ethnicity, acculturation, residence, education, and economic status. The primary objective of this study is to determine the influence of the 5 major determinants of human health (genetics, biology, behavior, psychology, society/environment) on the burden of T2D for Latino families. To achieve this objective, Mil Familias (www.milfamilias.sansum.org/) is establishing an observational cohort of 1000 Latino families, with at least one family member living with T2D. METHODS: Specially trained, bilingual Latino/a community health workers (Especialistas) recruit participant families and conduct research activities. Each individual family member will contribute data annually on over 100 different variables relating to their genetics, biology, psychology, behavior, and society/environment, creating a Latino-focused biobank ("Living Information Bank"). This observational cohort study is cross-sectional and longitudinal. Participants are divided into 4 groups: adults age ≥ 18 years with and without T2D, and children age ≥ 7 and < 18 years with and without T2D. Study activities take place through encounters between families and their Especialista. Encounters include screening/enrollment, informed consent, health promotion assessment, laboratory tests, questionnaires, physical activity monitoring, and reflection. DISCUSSION: By creating and providing the framework for the Cohort Establishment study, we intend to inform new approaches regarding equity and excellence in diabetes research and care. We will examine the complex set of factors that contribute to the burden of diabetes in Latino families and assess if cardio-metabolic disease risks go beyond the traditional biological and genetic factors. Breaking the code on the interplay of cardio-metabolic risk factors may help not only this fast growing segment of the U.S. population, but also other high-risk populations. TRIAL REGISTRATION: Study retrospectively registered at ClinicalTrials.gov (NCT03830840), 2/5/2019 (enrollment began 2/1/2019).

Farming for life: impact of medical prescriptions for fresh vegetables on cardiometabolic health for adults with or at risk of type 2 diabetes in a predominantly Mexican-American population.

INTRODUCTION: Poor diet is the leading cause of poor health in USA, with fresh vegetable consumption below recommended levels. We aimed to assess the impact of medical prescriptions for fresh (defined as picked within 72 hours) vegetables, at no cost to participants on cardiometabolic outcomes among adults (predominantly Mexican-American women) with or at risk of type 2 diabetes (T2D). METHODS: Between February 2019 and March 2020, 159 participants (122 female, 75% of Mexican heritage, 31% with non-insulin treated T2D, age 52.5 (13.2) years) were recruited using community outreach materials in English and Spanish, and received prescriptions for 21 servings/week of fresh vegetable for 10 weeks. Pre-post comparisons were made of weight; waist circumference; blood pressure; Hemoglobin A1c (HbA1c, a measure of long-term blood glucose control); self-reported sleep, mood and pain; vegetable, tortilla and soda consumption. After obtaining devices for this study, 66 of 72 participants asked, agreed to wear blinded continuous glucose monitors (CGM). RESULTS: Paired data were available for 131 participants. Over 3 months, waist circumference fell (-0.77 (95% CI -1.42 to 0.12) cm, p=0.022), as did systolic blood pressure (SBP) (-2.42 (95% CI -4.56 to 0.28) mm Hg, p=0.037), which was greater among individuals with baseline SBP >130 mm Hg (-7.5 (95% CI -12.4 to 2.6) mm Hg, p=0.005). Weight reduced by -0.4 (-0.7 to -0.04) kg, p=0.029 among women. For participants with baseline HbA1c >7.0%, HbA1c fell by -0.35 (-0.8 to -0.1), p=0.009. For participants with paired CGM data (n=40), time in range 70-180 mg/dL improved (from 97.4% to 98.9%, p<0.01). Food insecurity (p<0.001), tortilla (p<0.0001) and soda (p=0.013) consumption significantly decreased. Self-reported sleep, mood and pain level scores also improved (all p<0.01). CONCLUSIONS: Medical prescriptions for fresh vegetables were associated with clinically relevant improvements in cardiovascular risk factors and quality of life variables (sleep, mood and pain level) in adults (predominantly Mexican-American and female) with or at risk of T2D. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03940300.

Investigation of the Accuracy of 18 Marketed Blood Glucose Monitors.

OBJECTIVE: Cleared blood glucose monitors (BGMs) for personal use may not always deliver levels of accuracy currently specified by international and U.S. regulatory bodies. This study's objective was to assess the accuracy of 18 such systems cleared by the U.S. Food and Drug Administration representing approximately 90% of commercially available systems used from 2013 to 2015. RESEARCH DESIGN AND METHODS: A total of 1,035 subjects were recruited to have a capillary blood glucose (BG) level measured on six different systems and a reference capillary sample prepared for plasma testing at a reference laboratory. Products were obtained from consumer outlets and tested in three triple-blinded studies. Each of the three participating clinical sites tested a different set of six systems for each of the three studies in a round-robin. In each study, on average, a BGM was tested on 115 subjects. A compliant BG result was defined as within 15% of a reference plasma value (for BG ≥100 mg/dL [5.55 mmol/L]) or within 15 mg/dL (0.83 mmol/L) (for BG <100 mg/dL [5.55 mmol/L]). The proportion of compliant readings in each study was compared against a predetermined accuracy standard similar to, but more lenient than, current regulatory standards. Other metrics of accuracy included the overall compliance proportion; the proportion of extreme outlier readings differing from the reference value by >20%; modified Bland-Altman analysis including average bias, coefficient of variation, and 95% limits of agreement; and proportion of readings with no clinical risk as determined by the Surveillance Error Grid. RESULTS: The different accuracy metrics produced almost identical BGM rankings. Six of the 18 systems met the predetermined accuracy standard in all three studies, 5 systems met it in two studies, and 3 met it in one study. Four BGMs did not meet the accuracy standard in any of the three studies. CONCLUSIONS: Cleared BGMs do not always meet the level of analytical accuracy currently required for regulatory clearance. This information could assist patients, professionals, and payers in choosing products and regulators in evaluating postclearance performance.

Twelve-Week 24/7 Ambulatory Artificial Pancreas With Weekly Adaptation of Insulin Delivery Settings: Effect on Hemoglobin A1c and Hypoglycemia.

OBJECTIVE: Artificial pancreas (AP) systems are best positioned for optimal treatment of type 1 diabetes (T1D) and are currently being tested in outpatient clinical trials. Our consortium developed and tested a novel adaptive AP in an outpatient, single-arm, uncontrolled multicenter clinical trial lasting 12 weeks. RESEARCH DESIGN AND METHODS: Thirty adults with T1D completed a continuous glucose monitor (CGM)-augmented 1-week sensor-augmented pump (SAP) period. After the AP was started, basal insulin delivery settings used by the AP for initialization were adapted weekly, and carbohydrate ratios were adapted every 4 weeks by an algorithm running on a cloud-based server, with automatic data upload from devices. Adaptations were reviewed by expert study clinicians and patients. The primary end point was change in hemoglobin A1c (HbA1c). Outcomes are reported adhering to consensus recommendations on reporting of AP trials. RESULTS: Twenty-nine patients completed the trial. HbA1c, 7.0 ± 0.8% at the start of AP use, improved to 6.7 ± 0.6% after 12 weeks (-0.3, 95% CI -0.5 to -0.2, P < 0.001). Compared with the SAP run-in, CGM time spent in the hypoglycemic range improved during the day from 5.0 to 1.9% (-3.1, 95% CI -4.1 to -2.1, P < 0.001) and overnight from 4.1 to 1.1% (-3.1, 95% CI -4.2 to -1.9, P < 0.001). Whereas carbohydrate ratios were adapted to a larger extent initially with minimal changes thereafter, basal insulin was adapted throughout. Approximately 10% of adaptation recommendations were manually overridden. There were no protocol-related serious adverse events. CONCLUSIONS: Use of our novel adaptive AP yielded significant reductions in HbA1c and hypoglycemia.

Feasibility of Long-Term Closed-Loop Control: A Multicenter 6-Month Trial of 24/7 Automated Insulin Delivery.

BACKGROUND: In the past few years, the artificial pancreas-the commonly accepted term for closed-loop control (CLC) of blood glucose in diabetes-has become a hot topic in research and technology development. In the summer of 2014, we initiated a 6-month trial evaluating the safety of 24/7 CLC during free-living conditions. RESEARCH DESIGN AND METHODS: Following an initial 1-month Phase 1, 14 individuals (10 males/4 females) with type 1 diabetes at three clinical centers in the United States and one in Italy continued with a 5-month Phase 2, which included 24/7 CLC using the wireless portable Diabetes Assistant (DiAs) developed at the University of Virginia Center for Diabetes Technology. Median subject characteristics were age 45 years, duration of diabetes 27 years, total daily insulin 0.53 U/kg/day, and baseline HbA1c 7.2% (55 mmol/mol). RESULTS: Compared with the baseline observation period, the frequency of hypoglycemia below 3.9 mmol/L during the last 3 months of CLC was lower: 4.1% versus 1.3%, P < 0.001. This was accompanied by a downward trend in HbA1c from 7.2% (55 mmol/mol) to 7.0% (53 mmol/mol) at 6 months. HbA1c improvement was correlated with system use (Spearman r = 0.55). The user experience was favorable with identified benefit particularly at night and overall trust in the system. There were no serious adverse events, severe hypoglycemia, or diabetic ketoacidosis. CONCLUSION: We conclude that CLC technology has matured and is safe for prolonged use in patients' natural environment. Based on these promising results, a large randomized trial is warranted to assess long-term CLC efficacy and safety.

Randomized Crossover Comparison of Personalized MPC and PID Control Algorithms for the Artificial Pancreas.

OBJECTIVE: To evaluate two widely used control algorithms for an artificial pancreas (AP) under nonideal but comparable clinical conditions. RESEARCH DESIGN AND METHODS: After a pilot safety and feasibility study (n = 10), closed-loop control (CLC) was evaluated in a randomized, crossover trial of 20 additional adults with type 1 diabetes. Personalized model predictive control (MPC) and proportional integral derivative (PID) algorithms were compared in supervised 27.5-h CLC sessions. Challenges included overnight control after a 65-g dinner, response to a 50-g breakfast, and response to an unannounced 65-g lunch. Boluses of announced dinner and breakfast meals were given at mealtime. The primary outcome was time in glucose range 70-180 mg/dL. RESULTS: Mean time in range 70-180 mg/dL was greater for MPC than for PID (74.4 vs. 63.7%, P = 0.020). Mean glucose was also lower for MPC than PID during the entire trial duration (138 vs. 160 mg/dL, P = 0.012) and 5 h after the unannounced 65-g meal (181 vs. 220 mg/dL, P = 0.019). There was no significant difference in time with glucose <70 mg/dL throughout the trial period. CONCLUSIONS: This first comprehensive study to compare MPC and PID control for the AP indicates that MPC performed particularly well, achieving nearly 75% time in the target range, including the unannounced meal. Although both forms of CLC provided safe and effective glucose management, MPC performed as well or better than PID in all metrics.

Multinational Home Use of Closed-Loop Control Is Safe and Effective.

OBJECTIVE: To evaluate the efficacy of a portable, wearable, wireless artificial pancreas system (the Diabetes Assistant [DiAs] running the Unified Safety System) on glucose control at home in overnight-only and 24/7 closed-loop control (CLC) modes in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: At six clinical centers in four countries, 30 participants 18-66 years old with type 1 diabetes (43% female, 96% non-Hispanic white, median type 1 diabetes duration 19 years, median A1C 7.3%) completed the study. The protocol included a 2-week baseline sensor-augmented pump (SAP) period followed by 2 weeks of overnight-only CLC and 2 weeks of 24/7 CLC at home. Glucose control during CLC was compared with the baseline SAP. RESULTS: Glycemic control parameters for overnight-only CLC were improved during the nighttime period compared with baseline for hypoglycemia (time <70 mg/dL, primary end point median 1.1% vs. 3.0%; P < 0.001), time in target (70-180 mg/dL: 75% vs. 61%; P < 0.001), and glucose variability (coefficient of variation: 30% vs. 36%; P < 0.001). Similar improvements for day/night combined were observed with 24/7 CLC compared with baseline: 1.7% vs. 4.1%, P < 0.001; 73% vs. 65%, P < 0.001; and 34% vs. 38%, P < 0.001, respectively. CONCLUSIONS: CLC running on a smartphone (DiAs) in the home environment was safe and effective. Overnight-only CLC reduced hypoglycemia and increased time in range overnight and increased time in range during the day; 24/7 CLC reduced hypoglycemia and increased time in range both overnight and during the day. Compared with overnight-only CLC, 24/7 CLC provided additional hypoglycemia protection during the day.