Traditional methods of blood glucose monitoring involve obtaining samples for measurement via laboratory methodology or point of care devices and require invasive collection techniques such as capillary stick, venipuncture, or the placement of intravenous catheters. Limitations of traditional methods include the limited information provided by intermittent testing and the stress associated with restraint and discomfort experienced by patients. The snapshot nature of the provided information restricts a clinician's ability to truly monitor trends in glucose concentrations over an extended period of time, influencing clinical decision making. The stress of invasive sampling can cause stress hyperglycemia in many veterinary species, complicating interpretation. Continuous interstitial glucose monitoring technology is widely used in the human medical field due to the expansive information provided in a minimally invasive manner. In recent years, the device technology has advanced and cost has improved, prompting application of these devices into the veterinary sector. Studies have shown good agreement between newer glucose monitoring systems and traditional methods in small animal patients with diabetes mellitus, allowing veterinarians to obtain comprehensive glucose data with minimal stress and discomfort to the patient. However, information regarding the use of this new technology in equine medicine is limited. The following study describes the evaluation of two widely available glucose monitoring systems, the Dexcom G6 and the FreeStyle Libre, in healthy adult horses. / Master of Science / Monitoring of glucose concentrations is essential for the diagnosis and monitoring of a variety of disorders within equine medicine. Traditional methods of obtaining samples for testing include capillary stick, venipuncture, or the placement of intravenous catheters, which can cause stress and discomfort to equine patients. The information obtained by this testing methodology only allows for intermittent assessment of glucose concentrations, limiting the amount of information available for clinicians to make clinical decisions. The use of continuous glucose monitoring systems in the human medical field have allowed clinicians to obtain continuous or near-continuous glucose concentrations, improving interpretation. These devices have nearly eliminated the need for blood sampling for glucose concentrations, instead relying on interstitial glucose concentrations which have been shown to compare favorably to blood concentrations. Studies in small animal veterinary species, such as dogs and cats, have shown good agreement between newer glucose monitoring systems and traditional methods in small animal patients with diabetes mellitus, allowing veterinarians to obtain comprehensive glucose data with minimal stress and discomfort to the patient. However, information regarding the use of this new technology in horses is limited. The study described in the manuscript following evaluates the use of two widely available glucose monitoring systems, the Dexcom G6 and the FreeStyle Libre, in healthy adult horse.

Introduction: Brief vigorous exercise can enhance glycemic control. Limited work has investigated the effect of simple, practical interventions that require no specialized equipment. We examined the effect of bodyweight exercise (BWE) on acute glycemic control using continuous glucose monitoring (Abbott Libre Sense) under controlled dietary conditions This study was registered as a clinical trial (NCT05144490). Methods: Twenty-seven healthy adults (8 males, 19 females; age: 23±3 y) completed two virtually supervised trials in random order ~1 wk apart. The trials involved an 11-min BWE protocol that consisted of five, 1-min bouts performed at a self-selected pace interspersed with 1-min active recovery periods or a non-exercise sitting control period (CON). Food intake was standardized for each participant using pre-packaged meals supplied over 24 h. Results: Mean rating of perceived exertion for BWE was 14±2 (6-20 scale). Mean HR over the 11-minute the BWE protocol was 147±14 bpm which corresponded to 75% of age-predicted maximal HR. Mean 24-h glucose after BWE and CON was not different (5.0±0.4 vs 5.0±0.5 mM respectively; p=0.39). Postprandial glucose responses were also not different between trials after ingestion of a 75 g glucose drink, lunch, dinner and breakfast meals after each intervention. Measures of glycemic variability were not different between conditions. Conclusion: A single session of BWE did not alter acute glycemic control in healthy, young adults. This study demonstrates the feasibility of conducting a remotely supervised BWE intervention using CGM under free-living conditions. Future studies should investigate the effect of repeated sessions of BWE training as well as responses in people with impaired glycemic control. / Thesis / Master of Science (MSc) / We investigated the effect of brief bodyweight exercise (BWE) on glycemic control. This refers to the ability to maintain blood sugar within a healthy range. Glycemic control was assessed with a small device called a continuous glucose monitor (CGM) that is inserted just below the skin. Healthy adults completed a virtually supervised 11-minute BWE protocol or an equivalent period of sitting. There was no difference in glycemic control measured over 24 hours following the BWE compared to sitting under standardized dietary conditions. Future studies should investigate the effect of repeated sessions of BWE training as well as responses in people with impaired glycemic control.

Physical activity is important for the management and treatment of type 2 diabetes (T2D). Interval exercise training has been shown to improve glycemic control in people with T2D; however, studies have generally utilized high volume protocols and/or specialized equipment that limit translation to a “real world” setting. The present proof-of-concept study examined the efficacy of brief, intermittent stair climbing exercise to improve indices of glycemic control in adults with T2D, using continuous glucose monitoring (CGM) under controlled dietary conditions. Each session involved 3 x 60-s bouts of vigorously ascending and slowly descending a single flight of stairs. This was set within a 10-min period, which otherwise involved walking for a warm-up, cool-down and recovery in between bouts. Data are reported for n=5 participants (52 ± 18 y, BMI: 31 ± 5 kg/m2, HbA1c: 6.6 ± 0.7 %; mean ± SD) who performed 18 training sessions over 6 weeks. Mean 24-h glucose and time spent in hyperglycemia (> 10 mmol/L) were unchanged after an acute session of stair climbing (p=0.38 and p=0.42, respectively) or after 6 weeks of training (p=0.15 and p=0.47, respectively). Measures of glycemic variability were improved in the 24-h period following a single session of stair climbing, based on reductions in the mean amplitude of glycemic excursions (MAGE) (4.4 ± 1.5 vs. 3.5 ± 1.0 mmol/L, p =0.02) and the standard deviation (SD) around the mean (1.7 ± 0.5 vs. 1.4 ± 0.5 mmol/L, p=0.02). There was a meal-specific improvement in postprandial hyperglycemia after training, with the incremental area under the curve (iAUC) of the lunchtime meal reduced by 36 ± 42 % (p=0.01). These preliminary results demonstrate the feasibility of stair climbing as a physical activity option for people with T2D, although the acute and chronic effects of this training on indices of glycemic control remain equivocal. / Thesis / Master of Science in Kinesiology / Physical activity is important for the management of type 2 diabetes (T2D). Interval training, which involves alternating periods of relatively intense exercise and recovery, can improve blood sugar control in adults with T2D. This has largely been shown in laboratory settings using specialized equipment and protocols that may not be practical or time-efficient. This small, proof-of-concept study examined whether brief, intermittent stair climbing exercise could improve blood sugar control in people with T2D. Average blood sugar measured over 24 hours was unchanged after a single bout of stair climbing and after 18 sessions of training performed over 6 weeks. However, stair-climbing exercise reduced blood sugar fluctuations in response to specific meals. These preliminary findings suggest that interval stair climbing is a feasible exercise option for adults with T2D, but the precise effects on blood sugar control remain to be clarified.

Critically ill patients often exhibit abnormal glycaemia that can lead to severe complications and potentially death. In critically ill adults, hyperglycaemia is a common problem that has been associated with increased morbidity and mortality. In contrast, critically ill infants often suffer from hypoglycaemia, which may cause seizures and permanent brain injury. Further complicating the matter, both of these conditions are diagnosed by blood glucose (BG) measurements, often taken several hours apart, and, as a result, these conditions can remain poorly managed or go completely undetected. Emerging ‘continuous’ glucose monitoring (CGM) devices with 1-5 minute measurement intervals have the potential to resolve many issues associated with conventional intermittent BG monitoring. The objective of this research was to investigate and develop methods and models to optimise the clinical use of CGM devices in critically ill patients. For critically ill adults, an in-silico study was conducted to quantify the potential benefits of introducing CGM devices into the intensive care unit (ICU). Mathematical models of CGM error characteristics were implemented with existing, clinically validated, models of the insulin-glucose regulatory system, to simulate the behaviour of CGM devices in critically ill patients. An alarm algorithm was also incorporated to provide a warning at the onset of predicted hypoglycaemia, allowing a virtual dextrose intervention to be administered as a preventative measure. The results of the in-silico study showed a potential reduction in nurse workload of approximately 75% and a significant reduction in hypoglycaemia, while also providing insight into the optimal rescue dose size and resulting dynamics of glucose recovery. During 2012, ten patients were recruited into a pilot clinical trial of CGM devices in critical care with a primary goal of assessing the reliability of CGM devices in this environment, with a specific interest in the effects of CGM device type and sensor site on sensor glucose (SG) data. Results showed the mean absolute relative difference of SG data across the cohort was between 12-24% and CGM devices were capable of monitoring some patients with a high degree of accuracy. However, certain illnesses, drugs and therapies can potentially affect sensor performance, and one particular set of results suggested severe oedema may have affected sensor performance. A novel and first of its kind metric, the Trend Compass was developed and used to assesses trend accuracy of SG in a mathematically precise fashion without approximation, and, importantly, does so independent of glucose level or sensor bias, unlike any other such metrics. In this analysis, the trend accuracy between CGM devices was typically good. A recent hypothesis suggesting that glucose complexity is associated with mortality was also investigated using the clinical CGM data. The results showed that complexity results from detrended fluctuation analysis (DFA) were influenced far more by CGM device type than patient outcome. In addition, the location of CGM sensors had no significant effect on complexity results in this data set. Thus, while this emerging analytical method has shown positive results in the literature, this analysis indicates that those results may be misleading given the impact of technology outweighing that of physiology. This particular result helps to further delineate the range of potential applications and insight that CGM devices might offer in this clinical scenario. In critically ill infants, CGM devices were used to investigate hypoglycaemia during the first 48 hours after birth. More than 50 CGM data sets were obtained from several studies of CGM in infants at risk of hypoglycaemia at the Waikato hospital neonatal ICU (NICU). In light of concerns regarding CGM accuracy, particularly during the first few hours of monitoring and/or at low BG levels, an alternative, novel calibration scheme was developed to increase the reliability of SG data. The recalibration algorithm maximised the value of very accurate calibration BG measurements from a blood gas analyser (BGA), by forcing SG data to pass through these calibration BG measurements. Recalibration increased all metrics of hypoglycaemia (number, duration, severity and hypoglycaemic index) as the factory CGM calibration was found to be reporting higher values at low BG levels due to its least squares calibration approach based on the assumption of a less accurate calibration glucose meter. Thus, this research defined new calibration methods to directly optimise the use of CGM devices in this clinical environment, where accurate reference BG measurements are available. Furthermore, this work showed that metrics such as duration or area under curve were far more robust to error than the typically used counted-incidence metrics, indicating how clinical assessment may have to change when using these devices. The impact of errors in calibration measurements on metrics used to classify hypoglycaemia was also assessed. Across the cohort, measurement error, particularly measurement bias, had a larger effect on hypoglycaemia metrics than delays in entering calibration measurements. However, for patients with highly variable glycaemia, timing error can have a significantly larger impact on output SG data than measurement error. Unusual episodes of hypoglycaemia could be successfully identified using a stochastic model, based on kernel density estimation, providing another level of information to aid decision making when assessing hypoglycaemia. Using the developed algorithms/tools, with CGM data from 161 infants, the incidence of hypoglycaemia was assessed and compared to results determined using BG measurements alone. Results from BG measurements showed that ~17% of BG measurements identified hypoglycaemia and over 80% of episodes occurred in the first day after birth. However, with concurrent BG and SG data available, the SG data consistently identified hypoglycaemia at a higher rate suggesting the BG measurements were not capturing some episodes. Duration of hypoglycaemia in SG data varied from 0-10+%, but was typically in the range 4-6%. Hypoglycaemia occurred most frequently on the first day after birth and an optimal measurement protocol for at risk infants would likely involve CGM for the first week after birth with frequent intermittent BG measurements for the first day. Overall, CGM devices have the potential to increase the understanding of certain glycaemic abnormalities and aid in the diagnosis/treatment of other conditions in critically ill patients. This research has used a range of prospective and retrospective clinical studies to develop methods to further optimise the use of CGM devices within the critically ill clinical environment, as well as delineating where they are less useful or less robust. These latter results clearly define areas where clinical practice needs to adapt when using these devices, as well as areas where device makers could target technological improvements for best effect. Although further investigations are required before these devices are regularly implemented in day-to-day clinical practice, as an observational tool they are capable of providing useful information that is not currently available with conventional intermittent BG monitoring.

Aerobic exercise interventions involving individuals with type 1 diabetes have had little positive effect on blood glucose control as reflected by hemoglobin A1c. The few existing interventions involving resistance exercise, either alone or combined with aerobic exercise, while small in sample size, have had better outcomes. The purpose of this research program was to examine the changes in blood glucose levels during activity and for 24 hours post-exercise (as measured by continuous glucose monitoring) when resistance exercise is performed, either on its own or combined with aerobic exercise, as compared to aerobic exercise alone or no exercise. Twelve physically active individuals with type 1 diabetes performed 5 separate exercise sessions in random order separated by at least five days: 1) no exercise/control; 2) aerobic exercise (45 minutes of treadmill running at 60% VO2peak); 3) resistance exercise (45 minutes of weight lifting – 3 sets of 8 repetitions of 7 different exercises); 4) aerobic then resistance exercise (2 and 3 combined with the aerobic exercise first); 5) resistance then aerobic exercise (2 and 3 combined with the resistance exercise first). We found that resistance exercise was associated with a lower risk of hypoglycemia during exercise, less carbohydrate intake during exercise, less post-exercise hyperglycemia and more frequent (but less severe) nocturnal hypoglycemia than aerobic exercise. When aerobic and resistance exercise were combined, performing resistance exercise prior to aerobic exercise (rather than the reverse) resulted in attenuated declines in blood glucose during aerobic exercise, accompanied by a lower need for carbohydrate supplementation during exercise and a trend towards milder post-exercise nocturnal hypoglycemia.

INTRODUCTION: Type 1 diabetes (T1D) is a lifelong disease that requires regular injection of insulin and blood glucose (BG) monitoring. Many diabetes technologies have been created to assist in the management of T1D, including insulin pumps and Continuous Glucose Monitoring (CGM). These systems have been shown to decrease treatment distress and improve glycemic control. However, the uptake of these systems is low due to both cost and other barriers such as discomfort of wear or psychosocial aspects. METHODS: A survey was administered to clinicians of people with diabetes to better understand their perception of patient related barriers to device use. This analysis compares two clusters of clinicians, named "Cautious" and "Ready" based on their readiness to promote CGM use in their patients. Both have positive attitudes towards technology, but the Cautious cluster perceives much higher barriers to device use in their patients than the Ready cluster. In this analysis, the individual barriers, prerequisites to CGM use, confidence in addressing barriers, and clinic staff resources are compared between clusters using independent means t-tests and Pearson chi-square analyses. RESULTS: Results indicate that the confidence in addressing the clinician-reported number 1 rated barrier to CGM use was significantly lower in the Cautious cluster. Also, most individual barriers were perceived significantly more heavily by clinicians in the Cautious cluster. No significant difference was found in prerequisites to CGM use or clinic staff resources between the clusters. DISCUSSION: Because no differences were found in clinician reported prerequisites to CGM use between clusters, it does not seem that the clinicians in the Cautious cluster expect more from their patients before using this technology. One possible explanation would be a clinical deficiency. However, since there was no difference in clinic staff resources, it is unlikely that the availability of these resources contributes to the increased perceived barriers. Thus, the problem may lie in the clinician themselves. One possible explanation for the increased perceived barriers by the Cautious cluster is their lack of confidence in addressing barriers. Our results show that the Cautious cluster is significantly less confident in addressing the #1 barrier their patients face to CGM use, which is most commonly listed as cost-related barriers such as cost of the device or insurance status. One possible solution to this lack of confidence in clinicians is increased education on ways to address and coach patients on cost-related barriers.

Achieving tight glucose control safely in type 1 diabetes with currently available methods of insulin delivery is challenging. Aggressive regimens carry an increased risk of hypoglycaemia, particularly overnight. Both alcohol consumption and exercise predispose further to low glucose levels. The demands are even greater in pregnancy where, in addition to limiting hypoglycaemia, avoidance of postprandial hyperglycaemia is critical to minimising adverse obstetric outcomes. The aim of my studies was to evaluate feasibility and safety of a closed-loop or ’artificial pancreas’ system linking insulin delivery with continuous glucose monitoring (CGM), in adults with type 1 diabetes in a controlled setting. Three randomised crossover studies compared closed-loop insulin delivery with conventional insulin pump therapy on two separate occasions, matched in meals and activities. During closed-loop visits, CGM values were entered into a computer containing a model predictive control algorithm which advised on basal insulin infusion for subcutaneous delivery, every 15 minutes. During control visits, usual insulin pump regimen was continued. The feasibility study evaluated overnight closed-loop in 12 adults (seven females, mean age 37.7 years, HbA1c 7.8%) following 60g- carbohydrate evening meal. A follow-up study assessed overnight closed-loop in 12 further adults (seven females, mean age 37.2 years, HbA1c 7.8%) following 100g-carbohydrate meal and (mean 564 ml) white wine. The third study evaluated 24 hours of closed-loop in 12 pregnant women (mean age 32.9 years, 19 to 23 weeks gestation, HbA1c 6.4%) during normal daily activities, including low and moderate intensity exercise. Activity and glucose levels were also measured during free-living. CGM performance during exercise was evaluated. Overnight closed-loop insulin delivery in adults, compared with conventional pump therapy, increased time spent with plasma glucose in target range (3.9−8.0 mmol/l) following both standard meal (81% versus 57%; p = 0.012) and large meal accompanied by alcohol (70% versus 46%; p = 0.012). Glycaemic variability, and time spent in hypo- and hyper- glycaemia were lowered. In pregnant women, day and night closed-loop insulin delivery was as effective as usual pump regimen (81% versus 81% time spent with plasma glucose 3.5−7.8 mmol/l; p = 0.754). Hypoglycaemia occurred following exercise, although closed-loop prevented nocturnal episodes. Glycaemic control during free-living was suboptimal, compared with controlled diet and exercise conditions. Accuracy of CGM was lower during exercise. In conclusion, these studies confirm the feasibility and efficacy of overnight closed-loop insulin delivery in adults with type 1 diabetes. Closed-loop is safe during pregnancy and may be beneficial in women with suboptimal glycaemic control. Meals and physical activity currently limit optimal daytime use of closed-loop.

Aerobic exercise interventions involving individuals with type 1 diabetes have had little positive effect on blood glucose control as reflected by hemoglobin A1c. The few existing interventions involving resistance exercise, either alone or combined with aerobic exercise, while small in sample size, have had better outcomes. The purpose of this research program was to examine the changes in blood glucose levels during activity and for 24 hours post-exercise (as measured by continuous glucose monitoring) when resistance exercise is performed, either on its own or combined with aerobic exercise, as compared to aerobic exercise alone or no exercise. Twelve physically active individuals with type 1 diabetes performed 5 separate exercise sessions in random order separated by at least five days: 1) no exercise/control; 2) aerobic exercise (45 minutes of treadmill running at 60% VO2peak); 3) resistance exercise (45 minutes of weight lifting – 3 sets of 8 repetitions of 7 different exercises); 4) aerobic then resistance exercise (2 and 3 combined with the aerobic exercise first); 5) resistance then aerobic exercise (2 and 3 combined with the resistance exercise first). We found that resistance exercise was associated with a lower risk of hypoglycemia during exercise, less carbohydrate intake during exercise, less post-exercise hyperglycemia and more frequent (but less severe) nocturnal hypoglycemia than aerobic exercise. When aerobic and resistance exercise were combined, performing resistance exercise prior to aerobic exercise (rather than the reverse) resulted in attenuated declines in blood glucose during aerobic exercise, accompanied by a lower need for carbohydrate supplementation during exercise and a trend towards milder post-exercise nocturnal hypoglycemia.

ABSTRACT Diabetes Mellitus (DM) embraces a group of metabolic diseases which main characteristic is the presence of high glucose levels in blood. It is one of the diseases with major social and health impact, both for its prevalence and also the consequences of the chronic complications that it implies. One of the research lines to improve the quality of life of people with diabetes is of technical focus. It involves several lines of research, including the development and improvement of devices to estimate "online" plasma glucose: continuous glucose monitoring systems (CGMS), both invasive and non-invasive. These devices estimate plasma glucose from sensor measurements from compartments alternative to blood. Current commercially available CGMS are minimally invasive and offer an estimation of plasma glucose from measurements in the interstitial fluid CGMS is a key component of the technical approach to build the artificial pancreas, aiming at closing the loop in combination with an insulin pump. Yet, the accuracy of current CGMS is still poor and it may partly depend on low performance of the implemented Calibration Algorithm (CA). In addition, the sensor-to-patient sensitivity is different between patients and also for the same patient in time. It is clear, then, that the development of new efficient calibration algorithms for CGMS is an interesting and challenging problem. The indirect measurement of plasma glucose through interstitial glucose is a main confounder of CGMS accuracy. Many components take part in the glucose transport dynamics. Indeed, physiology might suggest the existence of different local behaviors in the glucose transport process. For this reason, local modeling techniques may be the best option for the structure of the desired CA. Thus, similar input samples are represented by the same local model. The integration of all of them considering the input regions where they are valid is the final model of the whole data set. Clustering is t / Barceló Rico, F. (2012). Multimodel Approaches for Plasma Glucose Estimation in Continuous Glucose Monitoring. Development of New Calibration Algorithms [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/17173 / Palancia

The present study is based on the hypotheses that a better user experience in mobile applications increases the frequency of use among users, and that a higher frequency of use of continuous glucose monitoring systems leads to better health status in patients with diabetes.The purpose of this study is to understand how users perceive and interact with CGM software.The result of this study shows that existing CGM applications and the functionalities they provide are very much appreciated by the participants. Many of the user needs may however not have been met in one application alone, since a large proportion of the participants use more than one CGM application.This study highlights importance of providing options for customization in every aspect offunctionality due to the individuality of each user’s condition, and that the settings of such should consider minimizing the cognitive load for the user.