Subcutaneous Insulin Delivery Research Articles

New Dosage Form of Insulin: Review Article

Many patients with advanced type 2 diabetes mellitus (T2DM) and all patients with T1DM require insulin to keep blood glucose levels in the target range. The most common route of insulin administration is subcutaneous insulin injections. There are many ways to deliver insulin subcutaneously, such as vials and syringes, insulin pens, and insulin pumps. Though subcutaneous insulin delivery is the standard route of insulin administration, it is associated with injection pain, needle phobia, lipodystrophy, noncompliance, and peripheral hyperinsulinemia. Therefore, the need exists to deliver insulin in a minimally invasive or noninvasive way and in the most physiological way. Inhaled insulin was the first approved noninvasive and alternative way to deliver glucose, but it has been withdrawn from the market. Researchers are exploring technologies to enable noninvasive insulin delivery. Some of the routes for insulin administration that are under investigation are oral, buccal, nasal, peritoneal, and transdermal. This article has focused on different possible routes of insulin administration, their advantages and limitations, and the possible scope of the new drug development.

Perioperative Care of Patients Using Wearable Diabetes Devices.

The increasing prevalence of diabetes mellitus has been accompanied by a rapid expansion in wearable continuous glucose monitoring (CGM) devices and insulin pumps. Systems combining these components in a "closed loop," where interstitial glucose measurement guides automated insulin delivery (AID, or closed loop) based on sophisticated algorithms, are increasingly common. While these devices' efficacy in achieving near-normoglycemia is contributing to increasing usage among patients with diabetes, the management of these patients in operative and procedural environments remains understudied with limited published guidance available, particularly regarding AID systems. With their growing prevalence, practical management advice is needed for their utilization, or for the rational temporary substitution of alternative diabetes monitoring and treatments, during surgical care. CGM devices monitor interstitial glucose in real time; however, there are potential limitations to use and accuracy in the perioperative period, and, at the present time, their use should not replace regular point-of-care glucose monitoring. Avoiding perioperative removal of CGMs when possible is important, as removal of these prescribed devices can result in prolonged interruptions in CGM-informed treatments during and after procedures, particularly AID system use. Standalone insulin pumps provide continuous subcutaneous insulin delivery without automated adjustments for glucose concentrations and can be continued during some procedures. The safe intraoperative use of AID devices in their hybrid closed-loop mode (AID mode) requires the CGM component of the system to continue to communicate valid blood glucose data, and thus introduces the additional need to ensure this portion of the system is functioning appropriately to enable intraprocedural use. AID devices revert to non-AID insulin therapy modes when paired CGMs are disconnected or when the closed-loop mode is intentionally disabled. For patients using insulin pumps, we describe procedural factors that may compromise CGM, insulin pump, and AID use, necessitating a proactive transition to an alternative insulin regimen. Procedure duration and invasiveness is an important factor as longer procedures increase the risk of stress hyperglycemia, tissue malperfusion, and device malfunction. Whether insulin pumps should be continued through procedures, or substituted by alternative insulin delivery methods, is a complex decision that requires all parties to understand potential risks and contingency plans relating to patient and procedural factors. Currently available CGMs and insulin pumps are reviewed, and practical recommendations for safe glycemic management during the phases of perioperative care are provided.

Effects of subcutaneous vs. oral nanoparticle-mediated insulin delivery on hemostasis disorders in type 1 diabetes: A rat model study

Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.

Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs.

Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9-326.1) ng/mL with a Tmax of 60 (30-75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1-71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.

Exercising Safely with the MiniMed™ 780G Automated Insulin Delivery System.

The physical and psychological benefits of exercise are particularly pertinent to people with type 1 diabetes (T1D). The variability in subcutaneous insulin absorption and the delay in offset and onset in glucose lowering action impose limitations, given the rapidly varying insulin requirements with exercise. Simultaneously, there are challenges to glucose monitoring. Consequently, those with T1D are less likely to exercise because of concerns regarding glucose instability. While glucose control with exercise can be enhanced using automated insulin delivery (AID), all commercially available AID systems remain limited by the pharmacokinetics of subcutaneous insulin delivery. Although glycemic responses may vary with exercises of differing intensities and durations, the principles providing the foundation for guidelines include minimization of insulin on board before exercise commencement, judicious and timely carbohydrate supplementation, and when possible, a reduction in insulin delivered in anticipation of planned exercise. There is an increasing body of evidence in support of superior glucose control with AID over manual insulin dosing in people in T1D who wish to exercise. The MiniMed™ 780G AID system varies basal insulin delivery with superimposed automated correction boluses. It incorporates a temporary (elevated glucose) target of 8.3 mmol/L (150 mg/dL) and when it is functioning, the autocorrection boluses are stopped. As the device has recently become commercially available, there are limited data assessing glucose control with the MiniMed™ 780G under exercise conditions. Importantly, when exercise was planned and implemented within consensus guidelines, %time in range and %time below range targets were met. A practical approach to exercising with the device is provided with illustrative case studies. While there are limitations to spontaneity imposed on any AID device due to the pharmacokinetics associated with the subcutaneous delivery of current insulin formulations, the MiniMed™ 780G system provides people with T1D an excellent option for exercising safely if the appropriate strategies are implemented.

A comprehensive review of oral chitosan drug delivery systems: Applications for oral insulin delivery

Abstract Pharmaceutical scientists have long struggled to develop reliable and efficient systems of administering insulin orally due to multiple barriers, including stomach acidity, enzymatic degradation, and mucus barriers. However, various strategies were developed to avoid insulin degradation in the gastrointestinal tract (GIT) and promote membrane permeability and biological activity. Among these strategies, chitosan polymer-based carriers are widely researched due to their ability to protect insulin in the alimentary canal and deliver it effectively through the intestinal mucosa, improving its bioavailability. To improve chitosan properties, chemical and physical modifications have been developed, and recently, nanoparticles, microparticles, and beads of chitosan exhibited potential systems for oral insulin delivery (OID). This review facilitates an outline of the types of diabetes mellitus, insulin biosynthesis, and gastrointestinal barriers against oral insulin. Moreover, the limitations of subcutaneous insulin delivery and alternative routes of administration are also discussed. As an ideal and most convenient oral administration route, the challenges of safe insulin delivery through the GIT and strategies to elevate its bioavailability are highlighted. In addition, this review focuses on recent advancements in chitosan based carriers for OID and their potential future applications.

Multilayer track-etched membrane-based electroosmotic pump for drug delivery.

Herein, we report an electroosmotic pump (EOP) based on a multilayer track-etched polycarbonate (PC) membrane. A remarkable increase of maximum backpressure (198.2-2400mmH2 O) of a fundamental pump unit was obtained at 0.8mA, when the number of PC membranes was increased from 1 to 10. Meanwhile, the corresponding flow rate was increased from 80.3 to 111.7µL/min. Furthermore, multiple pump units were assembled in series to obtain a multistage EOP. For a three-stage EOP (EOP-3), the operating voltage and power can be decreased significantly by 52%-72% under different driving currents, with a minimum power of 26.7µW. Thus, EOP-3 can run stably over 35h at a pulse current of 0.1mA without the generation of gas bubbles. The pump was further integrated into a miniature device, which was successfully used to decrease the blood glucose level of diabetic rats by subcutaneous delivery of fast-acting insulin. This work brings a facile and efficient strategy to enhance the backpressure and lower the operating voltage and power of EOPs, which may find promising applications in drug delivery.

Robust controller for artificial pancreas for patients with type-1 diabetes

The target of this paper is to design a simple and an efficient controller for artificial pancreas (AP) system for blood glucose (BG) regulation in type-1 diabetic mellitus (T1DM) patient. Bergman’s intravenous model is chosen for the controller design as the model is minimum ordered model of T1DM patient. A multi-objective output feedback controller has been designed for AP system considering robustness, disturbance rejection, and transient criterion. Considering H∞, pole-placement, and H2 constraints, a control algorithm has been developed and has been solved using linear matrix inequality (LMI) technique. As a testing platform of the intravenous model-based designed controller, UVa/Padova T1DM metabolic simulator has been chosen which uses subcutaneous insulin delivery method. The controller has been tested in the presence of unannounced meal disturbances. Experimental results show that the controller regulates BG level very efficiently with lesser amount of insulin and avoids hypoglycemia effect. In the presence of external noises like glucose sensor noise and insulin pump error, the robustness of the controller has been checked. The performance of the controller has been compared with compound internal model control (IMC) strategy reported earlier for same meal scenario. The designed multi-objective controller gives better performance metrices than compound IMC controller.

Model-based subcutaneous insulin for glycemic control of pre-term infants in the neonatal intensive care unit

Hyperglycaemia is a common problem in neonatal intensive care units (NICUs). Achieving good control can result in better outcomes for patients. However, good control is difficult, where poor control and resulting hypoglycaemia reduces outcomes and confounds results. Clinically validated models can provide good control, and subcutaneous insulin delivery can provide more options for insulin therapy for clinicians. However, this combination has only been significantly utilised in adult outpatient diabetes, but could hold benefit for treating NICU infants. This research combines a well-validated NICU metabolic model with subcutaneous insulin kinetics models to assess the feasibility of a model-based approach. Clinical data from 12 very/extremely pre-mature infants was collected for an average study duration of 10.1 days. Blood glucose, interstitial and plasma insulin, as well as subcutaneous and local insulin were modelled, and patient-specific insulin sensitivity profiles were identified for each patient. Modelling error was low, where the cohort median [IQR] mean percentage error was 0.8 [0.3 3.4] %. For external validation, insulin sensitivity was compared to previous NICU cohorts using the same metabolic model, where overall levels of insulin sensitivity were similar. Overall, the combined system model accurately captured observed glucose and insulin dynamics, showing the potential for a model-based approach to glycaemic control using subcutaneous insulin in this cohort. The results justify further model validation and clinical trial research to explore a model-based protocol.

Hypoglycemia and glycemic variability of people with type 1 diabetes with lower and higher physical activity loads in free-living conditions using continuous subcutaneous insulin infusion with predictive low-glucose suspend system

IntroductionMaintaining glycemic control during and after physical activity (PA) is a major challenge in type 1 diabetes (T1D). This study compared the glycemic variability and exercise-related diabetic management strategies of...

Glycaemic control and novel technology management strategies in pregestational diabetes mellitus.

Pregestational diabetes (PGDM) is an increasingly common and complex condition that infers risk to both mother and infant. To prevent serious morbidity, strict glycaemic control is essential. The aim of this review is to review the glucose sensing and insulin delivering technologies currently available for women with PGDM. We reviewed online databases for articles relating to technology use in pregnancy using a combination of keywords and MeSH headings. Relevant articles are included below. A number of technological advancements have improved care and outcomes for women with PGDM. Real time continuous glucose monitoring (rtCGM) offers clear advantages in terms of infants size and neonatal intensive care unit admissions; and further benefits are seen when combined with continuous subcutaneous insulin delivery (insulin pump) and algorithms which continuously adjust insulin levels to glucose targets (hybrid closed loop). Other advancements including flash or intermittent scanning CGM (isCGM) and stand-alone insulin pumps do not confer as many advantages for women and their infants, however they are increasingly used outside of pregnancy and many women enter pregnancy already using these devices. This article offers a discussion of the most commonly used technologies in pregnancy and evaluates their current and future roles.

Model-based Glycemic Control Using Subcutaneous Insulin for Infants in Critical Care

Neonatal hyperglycaemia is common for infants in critical care, and can lead to increases in mortality and morbidity. Subcutaneous insulin delivery systems offer an easy way to control blood glucose (BG) to more normal levels. However, research on subcutaneous insulin models are lacking in this cohort. This paper presents a model combining validated NICU models with adult subcutaneous models for glycaemic control. Clinical data from 12 very/extremely pre-mature infants was collected for an average study duration of 10.1 days. Glucose, interstitial and plasma insulin, as well as subcutaneous and local insulin were modelled, and insulin sensitivity profiles were identified for each patient. Modelling error was low, where the cohort median [IQR] for mean percentage error was 0.8 [0.3-3.4] %. The model was able to capture glucose and insulin activity accurately, but further research should be undertaken to validate the model and its parameters, to explore the potential of subcutaneous insulin delivery under a model-based protocol.

Masticatory system-inspired microneedle theranostic platform for intelligent and precise diabetic management.

Integrated systems for diabetic theranostics present advanced technology to regulate diabetes yet still have critical challenges in terms of accuracy, long-term monitoring, and minimal invasiveness. Inspired by the feature and functions of animal masticatory system, we presented a biomimetic microneedle theranostic platform (MNTP) for intelligent and precise management of diabetes. The MNTP was supported by a miniatured circuit, which used microneedle arrays for on-demand skin penetration, enabling interstitial fluid exudation for simultaneous detection of glucose and physiological ions, and subcutaneous insulin delivery. Interstitial fluid exudation enabled sensing in oxygen-rich environment via the incorporated epidermal sensor functionalized with hybrid carbon nanomaterials. This feature addressed the biosafety issues due to implanted electrodes and the "oxygen-deficit" issues in vivo. The MNTP was demonstrated to accurately detect glucose and ions and deliver insulin to regulate hyperglycemia. The biomimetic and intelligent features of the MNTP endowed it as a highly advanced system for diabetes therapy.

Profound Sensitivity of the Liver to the Direct Effect of Insulin Allows Peripheral Insulin Delivery to Normalize Hepatic but Not Muscle Glucose Uptake in the Healthy Dog.

Endogenous insulin secretion is a key regulator of postprandial hepatic glucose metabolism, but this process is dysregulated in diabetes. Subcutaneous insulin delivery alters normal insulin distribution, causing relative hepatic insulin deficiency and peripheral hyperinsulinemia, a major risk factor for metabolic disease. Our aim was to determine whether insulin's direct effect on the liver is preeminent even when insulin is given into a peripheral vein. Postprandial-like conditions were created (hyperinsulinemia, hyperglycemia, and a positive portal vein to arterial glucose gradient) in healthy dogs. Peripheral (leg vein) insulin infusion elevated arterial and hepatic levels 8.0-fold and 2.8-fold, respectively. In one group, insulin's full effects were allowed. In another, insulin's indirect hepatic effects were blocked with the infusion of triglyceride, glucagon, and inhibitors of brain insulin action (intracerebroventricular) to prevent decreases in plasma free fatty acids and glucagon, while blocking increased hypothalamic insulin signaling. Despite peripheral insulin delivery the liver retained its full ability to store glucose, even when insulin's peripheral effects were blocked, whereas muscle glucose uptake markedly increased, creating an aberrant distribution of glucose disposal between liver and muscle. Thus, the healthy liver's striking sensitivity to direct insulin action can overcome the effect of relative hepatic insulin deficiency, whereas excess insulin in the periphery produces metabolic abnormalities in nonhepatic tissues.

A Look Into the Next Century After 100 Years of Insulin.

Being diagnosed with diabetes can be challenging, particularly if we do not know a similar individual with the same disease. A person's life may suddenly change and he/she may not be aware of the possibilities or treatment options available or the questions that need to be asked; hence, instead of looking for assistance, many people hide their diabetic condition from others. But due to innovative devices, individuals no longer need to be concerned. Various gadgets today help provision insulin via a subcutaneous route, for example, an insulin pen, pump, vial, or syringe. Despite being the most familiar way to provide insulin, subcutaneous insulin delivery is linked to needle pain, injection anxiety, lipodystrophy, compliance issues, and peripheral hyperinsulinemia; thus, there is a need for an insulin delivery system that is both less invasive and more biological. The discovery of insulin and its uses are linked to the beginning of diabetes treatment. Initially, the delivery of insulin was accomplished using giant, heavy, reusable syringes equipped with plungers, barrels, and wide-bore needles. To prepare these syringes and needles for reuse, these were boiled. The development of insulin syringes, which are presently in use and have revolutionized healthcare, resulted from manufacturers' continued efforts and technological innovations. Injections of insulin may become obsolete if research from the University of Alberta is successful. Researchers from the University of Alberta claim that insulin-producing cells developed from stem cells are secure for transplantation to wean diabetes patients from injectable insulin permanently. In a significant mice experiment, experts demonstrated the role of the inceptor (insulin inhibitory receptor), which protects the beta cells from insulin pathway activation. Insulin resistance in diabetes may be exacerbated by the inceptor's ability to block insulin signaling. Technologies known as "smart insulin" (glucose-responsive insulin) deliver insulin according to the patient's glycemic condition without needing additional monitoring by the patient or the physician in charge. The review of insulin administration devices and several cutting-edge insulin-related ideas are the main topics of this article.

Vasodilatory effects of glucagon: A possible new approach to enhanced subcutaneous insulin absorption in artificial pancreas devices.

Patients with diabetes mellitus type 1 depend on exogenous insulin to keep their blood glucose concentrations within the desired range. Subcutaneous bihormonal artificial pancreas devices that can measure glucose concentrations continuously and autonomously calculate and deliver insulin and glucagon infusions is a promising new treatment option for these patients. The slow absorption rate of insulin from subcutaneous tissue is perhaps the most important factor preventing the development of a fully automated artificial pancreas using subcutaneous insulin delivery. Subcutaneous insulin absorption is influenced by several factors, among which local subcutaneous blood flow is one of the most prominent. We have discovered that micro-doses of glucagon may cause a substantial increase in local subcutaneous blood flow. This paper discusses how the local vasodilative effects of micro-doses of glucagon might be utilised to improve the performance of subcutaneous bihormonal artificial pancreas devices. We map out the early stages of our hypothesis as a disruptive novel approach, where we propose to use glucagon as a vasodilator to accelerate the absorption of meal boluses of insulin, besides using it conventionally to treat hypoglycaemia.

Automated insulin delivery systems: from early research to routine care of type 1 diabetes.

Automated insulin delivery (AID) systems, so-called closed-loop systems or artificial pancreas, are based upon the concept of insulin supply driven by blood glucose levels and their variations according to body glucose needs, glucose intakes and insulin action. They include a continuous glucose monitoring device which provides a signal to a control algorithm tuning insulin delivery from an infusion pump. The control algorithm is the key of the system since it commands insulin administration in order to maintain blood glucose in a predefined target range and close to a near-normal glucose level. The last two decades have shown dramatic advances toward the use in free life of AID systems for routine care of type 1 diabetes through step-by-step demonstrations of feasibility, safety and efficacy in successive hospital, transitional and outpatient trials. Because of the constraints of pharmacokinetics and dynamics of subcutaneous insulin delivery, the currently available AID systems are all 'hybrid' or 'semi-automated' insulin delivery systems with a need of meal and exercise announcements in order to anticipate rapid glucose variations through pre-meal bolus or pre-exercise reduction of infusion rate. Nevertheless, these AID systems significantly improve time spent in a near-normal range with a reduction of the risk of hypoglycemia and the mental load of managing diabetes in everyday life, representing a milestone in insulin therapy. Expected progression toward fully automated, further miniaturized and integrated, possibly implantable on long-term and more physiological closed-loop systems paves the way for a functional cure of type 1 diabetes.

Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial.

Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy according to local clinical practice (control group). Study treatment was administered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6-10.0 mmol/L). Forty-five patients were enrolled and assigned to the closed-loop (n = 23) or the control (n = 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P < 0.001). No episodes of severe hypoglycemia (<3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia.

PP439 Data Driven Subgroups Of Patients With Type 1 Diabetes Based On Health Technology For Insulin Delivery

IntroductionPatients with type 1 diabetes (T1D) require the administration of insulin to maintain glycemic control. Currently, two modes of subcutaneous insulin delivery have gained wider acceptance: multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII). Randomized controlled trials have shown that CSII is associated with a slightly lower glycated hemoglobin (HbA1c) level when compared with MDI.The case study on diabetes by the H2020 Next Generation Health Technology Assessment project aims to link evidence from randomized controlled trials to real-world data to estimate the impact of health technology on specific subgroups of patients, as a first step in building prediction models to personalize treatment strategies. This work aims to assess whether patients with T1D can be stratified according to the use of health technology for insulin delivery and associated glycemic control from real-world data.MethodsWe used a longitudinal prospective data repository of T1D patients from 83 clinics in the United States (T1D exchange). A data-driven two-step clustering analysis was done on adult individuals (n = 8,034) with more than five years of disease duration. Clusters were based on body mass index (BMI), sex, age at diagnosis, diabetes duration, HbA1c level, and insulin delivery method. The optimal number of clusters was estimated based on silhouette width.ResultsWe identified the following four clusters of T1D patients characterized by differences in gender and insulin delivery method: men and women with insulin injections or pens and men and women with CSII. Individuals that used CSII had lower HbA1c levels, a higher BMI, and longer diabetes duration than those using Injections or pens.ConclusionsThis preliminary work identified subgroups of T1D patients linked to insulin delivery methods. Future research includes the study of complications associated with different clusters and additional data sources. While the data were sourced from the T1D Exchange, the analyses, content, and conclusions presented have not been reviewed or approved by the T1D Exchange.

A Randomized Crossover Trial Comparing Glucose Control During Moderate-Intensity, High-Intensity, and Resistance Exercise With Hybrid Closed-Loop Insulin Delivery While Profiling Potential Additional Signals in Adults With Type 1 Diabetes.

To compare glucose control with hybrid closed-loop (HCL) when challenged by high intensity exercise (HIE), moderate intensity exercise (MIE), and resistance exercise (RE) while profiling counterregulatory hormones, lactate, ketones, and kinetic data in adults with type 1 diabetes. This study was an open-label multisite randomized crossover trial. Adults with type 1 diabetes undertook 40 min of HIE, MIE, and RE in random order while using HCL (Medtronic MiniMed 670G) with a temporary target set 2 h prior to and during exercise and 15 g carbohydrates if pre-exercise glucose was <126 mg/dL to prevent hypoglycemia. Primary outcome was median (interquartile range) continuous glucose monitoring time-in-range (TIR; 70-180 mg/dL) for 14 h post-exercise commencement. Accelerometer data and venous glucose, ketones, lactate, and counterregulatory hormones were measured for 280 min post-exercise commencement. Median TIR was 81% (67, 93%), 91% (80, 94%), and 80% (73, 89%) for 0-14 h post-exercise commencement for HIE, MIE, and RE, respectively (n = 30), with no difference between exercise types (MIE vs. HIE; P = 0.11, MIE vs. RE, P = 0.11; and HIE vs. RE, P = 0.90). Time-below-range was 0% for all exercise bouts. For HIE and RE compared with MIE, there were greater increases, respectively, in noradrenaline (P = 0.01 and P = 0.004), cortisol (P < 0.001 and P = 0.001), lactate (P ≤ 0.001 and P ≤ 0.001), and heart rate (P = 0.007 and P = 0.015). During HIE compared with MIE, there were greater increases in growth hormone (P = 0.024). Under controlled conditions, HCL provided satisfactory glucose control with no difference between exercise type. Lactate, counterregulatory hormones, and kinetic data differentiate type and intensity of exercise, and their measurement may help inform insulin needs during exercise. However, their potential utility as modulators of insulin dosing will be limited by the pharmacokinetics of subcutaneous insulin delivery.