The promising future of insulin therapy in diabetes mellitus.

The first therapeutic use of insulin by Frederick Banting and Charles Best in 1921 revolutionized the management of type 1 diabetes and considerably changed the lives of many patients with other types of diabetes. In the past 100 years, significant pharmacological advances took place in the field of insulin therapy, bringing closer the goal of optimal glycemic control along with decreased diabetes-related complications. Despite these developments, several challenges remain, such as increasing treatment flexibility, reducing iatrogenic hypoglycemia, and optimizing patient quality of life. Ongoing innovations in insulin therapy (e.g., new insulin analogs, alternative routes of insulin administration, and closed-loop technology) endeavor to overcome these hurdles and change the landscape of diabetes mellitus management. This report highlights recent advances made in the field of insulin therapy and discusses future perspectives.

Perceptions and expectations of adults with type 1 diabetes for the use of artificial pancreas systems with and without glucagon addition: Results of an online survey.

BACKGROUND AND AIMS: The first hybrid artificial pancreas (AP) systems with insulin only (mono-hormonal) have recently reached the market while next generations systems are under development including those with glucagon addition (bi-hormonal). Understanding the expectations and impressions of future potential users about AP systems is important for optimal use of this clinically effective emerging technology. METHODS AND RESULTS: An online survey about AP systems which consisted of 50 questions was addressed to people with type 1 diabetes in the province of Quebec, Canada. Surveys were completed by 123 respondents with type 1 diabetes (54% women, mean (SD) age 40.2 (14.4) y.o., diabetes duration 23.7 (14.1) years, 58% insulin pump users and 43% glucose sensor users). Of the respondents, 91% understood how AP systems work, 79% trusted them with correct insulin dosing, 73% were willing to replace their current treatment with AP and 80% expected improvement in quality of life. Anxiety about letting an algorithm control their glucose levels was expressed by 18% while the option of ignoring or modifying AP instructions was favoured by 88%. As for bi-hormonal AP systems, 83% of respondents thought they would be useful to further reduce hypoglycemic risks. CONCLUSIONS: Overall, respondents expressed positive views about AP systems use and high expectations for a better quality of life, glycemic control and hypoglycemia reduction. Data from this survey could be useful to health care professionals and developers of AP systems.

Comparison of two carbohydrate intake strategies to improve glucose control during exercise in adolescents and adults with type 1 diabetes.

BACKGROUND AND AIMS: During aerobic physical activity (PA), hypoglycemia is common in people with type 1 diabetes (T1D). Few studies have compared the effectiveness of different carbohydrate (CHO) intake strategies to prevent PA-induced hypoglycemia. Our objective was to compare the efficacy of two CHO intake strategies, same total amount but different CHO intake timing, to maintain glucose levels in the target range (4.0-10.0 mmol/L) during PA in people with T1D. METHODS AND RESULTS: An open-label, randomized, crossover study in 33 participants (21 adults; 12 adolescents). Participants practiced 60 min PA sessions (ergocyle) at 60% VO2peak 3.5 h after lunch comparing an intake of 0.5 g of CHO per kg of body weight applied in a pre-PA single CHO intake (SCI) or in a distributed CHO intake (DCI) before and during PA. The percentage of time spent in glucose level target range during PA was not different between the two strategies (SCI: 75 ± 35%; DCI: 87 ± 26%; P = 0.12). Hypoglycemia (<4.0 mmol/L) occurred in 4 participants (12%) with SCI compared to 6 participants (18%) with DCI (P = 0.42). The SCI strategy led to a higher increase (P = 0.01) and variability of glucose levels (P = 0.04) compared with DCI. CONCLUSIONS: In people living with T1D, for a 60 min moderate aerobic PA in the post-absorptive condition, a 0.5 g/kg CHO intake helped most participants maintain acceptable glycemic control with both strategies. No clinically significant difference was observed between the SCI and DCI strategies. ClinicalTrials.gov Identifier: NCT03214107 (July 11, 2017).

A single-blind, randomised, crossover study to reduce hypoglycaemia risk during postprandial exercise with closed-loop insulin delivery in adults with type 1 diabetes: announced (with or without bolus reduction) vs unannounced exercise strategies.

AIMS/HYPOTHESIS: For individuals living with type 1 diabetes, closed-loop insulin delivery improves glycaemic control. Nonetheless, maintenance of glycaemic control during exercise while a prandial insulin bolus remains active is a challenge even to closed-loop systems. We investigated the effect of exercise announcement on the efficacy of a closed-loop system, to reduce hypoglycaemia during postprandial exercise. METHODS: A single-blind randomised, crossover open-label trial was carried out to compare three strategies applied to a closed-loop system at mealtime in preparation for exercise taken 90 min after eating at a research testing centre: (1) announced exercise to the closed-loop system (increases target glucose levels) in addition to a 33% reduction in meal bolus (A-RB); (2) announced exercise to the closed-loop system and a full meal bolus (A-FB); (3) unannounced exercise and a full meal bolus (U-FB). Participants performed 60 min of exercise at 60% [Formula: see text] 90 min after eating breakfast. The investigators were not blinded to the interventions. However, the participants were blinded to the sensor glucose readings and to the insulin infusion rates throughout the intervention visits. RESULTS: The trial was completed by 37 adults with type 1 diabetes, all using insulin pumps: mean±SD, 40.0 ± 15.0 years of age, HbA1c 57.1 ± 10.8 mmol/mol (7.3 ± 1.0%). Reported results were based on plasma glucose values. During exercise and the following 1 h recovery period, time spent in hypoglycaemia (<3.9 mmol/l; primary outcome) was reduced with A-RB (mean ± SD; 2.0 ± 6.2%) and A-FB (7.0 ± 12.6%) vs U-FB (13.0 ± 19.0%; p < 0.0001 and p = 0.005, respectively). During exercise, A-RB had the least drop in plasma glucose levels: A-RB -0.3 ± 2.8 mmol/l, A-FB -2.6 ± 2.9 mmol/l vs U-FB -2.4 ± 2.7 mmol/l (p < 0.0001 and p = 0.5, respectively). Comparison of A-RB vs U-FB revealed a decrease in the time spent in target (3.9-10 mmol/l) by 12.7% (p = 0.05) and an increase in the time spent in hyperglycaemia (>10 mmol/l) by 21% (p = 0.001). No side effects were reported during the applied strategies. CONCLUSIONS/INTERPRETATION: Combining postprandial exercise announcement, which increases closed-loop system glucose target levels, with a 33% meal bolus reduction significantly reduced time spent in hypoglycaemia compared with the other two strategies, yet at the expense of more time spent in hyperglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT0285530 FUNDING: JDRF (2-SRA-2016-210-A-N), the Canadian Institutes of Health Research (354024) and the Fondation J.-A. DeSève chair held by RR-L.

Single-Hormone Artificial Pancreas Use in Diabetes: Clinical Efficacy and Remaining Challenges.

IN BRIEF Artificial pancreas systems are rapidly developing and constitute the most promising technology for insulin-requiring diabetes management. Single-hormone systems (SH-AP) that deliver only insulin and have a hybrid design that necessitates patients' interventions around meals and exercise are the first to appear on the market. Trials with SH-AP have demonstrated improvement in time spent with blood glucose levels within target ranges, with a concomitant decrease in hypoglycemia. Longer and larger trials involving different patient populations are ongoing to further advance this important technology.

The challenges of achieving postprandial glucose control using closed-loop systems in patients with type 1 diabetes.

For patients with type 1 diabetes, closed-loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared with conventional therapy. Yet, reducing glucose excursion and simplification of prandial insulin doses remain a challenge. The objective of this literature review is to examine current meal-time strategies in the context of automated delivery systems in adults and children with type 1 diabetes. Current challenges and considerations for post-meal glucose control will also be discussed. Despite promising results with meal detection, the fully automated CLS has yet failed to provide comparable glucose control to CLS with carbohydrate-matched bolus in the post-meal period. The latter strategy has been efficient in controlling post-meal glucose using different algorithms and in various settings, but at the cost of a meal carbohydrate counting burden for patients. Further improvements in meal detection algorithms or simplified meal-priming boluses may represent interesting avenues. The greatest challenges remain in regards to the pharmacokinetic and dynamic profiles of available rapid insulins as well as sensor accuracy and lag-time. New and upcoming faster acting insulins could provide important benefits. Multi-hormone CLS (eg, dual-hormone combining insulin with glucagon or pramlintide) and adjunctive therapy (eg, GLP-1 and SGLT2 inhibitors) also represent promising options. Meal glucose control with the artificial pancreas remains an important challenge for which the optimal strategy is still to be determined.

Glucagon in artificial pancreas systems: Potential benefits and safety profile of future chronic use.

The role of glucagon in the pathophysiology of diabetes has long been recognized, although its approved clinical use has so far been limited to the emergency treatment of severe hypoglycaemia. A novel use of glucagon as intermittent mini-boluses is proposed in the dual-hormone version (insulin and glucagon) of the external artificial pancreas. Short-term studies suggest that the incorporation of glucagon into artificial pancreas systems has the potential to further decrease hypoglycaemic risk and improve overall glucose control; however, the potential long-term safety and benefits also need to be investigated given the recognized systemic effects of glucagon. In the present report, we review the available animal and human data on the physiological functions of glucagon, as well as its pharmacological use, according to dosing and duration (acute and chronic). Along with its main role in hepatic glucose metabolism, glucagon affects the cardiovascular, renal, pulmonary and gastrointestinal systems. It has a potential role in weight reduction through its central satiety function and its role in increasing energy expenditure. Most of the pharmacological studies investigating the effects of glucagon have used doses exceeding 1 mg, in contrast to the mini-boluses used in the artificial pancreas. The available data are reassuring but comprehensive human studies using small but chronic glucagon doses that are close to the physiological ranges are lacking. We propose a list of variables that could be monitored during long-term trials of the artificial pancreas. Such trials should address the questions about the risk-benefit ratio of chronic glucagon use.

Can somatostatin antagonism prevent hypoglycaemia during exercise in type 1 diabetes?

The prevention and management of exercise-induced hypoglycaemia remains a challenge for patients with type 1 diabetes. Strategies involving changes to insulin dosing and/or carbohydrate consumption in anticipation of or during different types of exercise have proved to be helpful but not sufficient to fully prevent the hypoglycaemic risk. Meanwhile, the defect in glucagon secretion in response to hypoglycaemia in diabetes and the contributory role of somatostatin to this dysregulation constitute an important therapeutic target. In this issue of Diabetologia (DOI 10.1007/s00125-016-3953-0 ), Leclair et al show that selective somatostatin receptor 2 antagonists can enhance glucagon secretion in rats with streptozotocin-induced diabetes during exercise. The implications of their interesting findings are discussed, as well as limitations and potential for clinical applications, together with other glucagon-based options for tackling exercise-induced hypoglycaemia in diabetes.

Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial.

AIMS/HYPOTHESIS: The aim of this study was to assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared with the single-hormone (insulin alone) artificial pancreas during two types of exercise. METHODS: An open-label randomised crossover study comparing both systems in 17 adults with type 1 diabetes (age, 37.2 ± 13.6 years; HbA1c, 8.0 ± 1.0% [63.9 ± 10.2 mmol/mol]) during two exercise types on an ergocycle and matched for energy expenditure: continuous (60% [Formula: see text] for 60 min) and interval (2 min alternating periods at 85% and 50% [Formula: see text] for 40 min, with two 10 min periods at 45% [Formula: see text] at the start and end of the session). Blocked randomisation (size of four) with a 1:1:1:1 allocation ratio was computer generated. The artificial pancreas was applied from 15:30 hours until 19:30 hours; exercise was started at 18:00 hours and announced 20 min earlier to the systems. The study was conducted at the Institut de recherches cliniques de Montréal. RESULTS: During single-hormone control compared with dual-hormone control, exercise-induced hypoglycaemia (plasma glucose <3.3 mmol/l with symptoms or <3.0 mmol/l regardless of symptoms) was observed in four (23.5%) vs two (11.8%) interventions (p = 0.5) for continuous exercise and in six (40%) vs one (6.25%) intervention (p = 0.07) for interval exercise. For the pooled analysis (single vs dual hormone), the median (interquartile range) percentage time spent at glucose levels below 4.0 mmol/l was 11% (0.0-46.7%) vs 0% (0-0%; p = 0.0001) and at glucose levels between 4.0 and 10.0 mmol/l was 71.4% (53.2-100%) vs 100% (100-100%; p = 0.003). Higher doses of glucagon were needed during continuous (0.126 ± 0.057 mg) than during interval exercise (0.093 ± 0.068 mg) (p = 0.03), with no reported side-effects in all interventions. CONCLUSIONS/INTERPRETATION: The dual-hormone artificial pancreas outperformed the single-hormone artificial pancreas in regulating glucose levels during announced exercise in adults with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01930110 FUNDING: : Société Francophone du Diabète and Diabète Québec.

Rfx6 directs islet formation and insulin production in mice and humans.

Insulin from the beta-cells of the pancreatic islets of Langerhans controls energy homeostasis in vertebrates, and its deficiency causes diabetes mellitus. During embryonic development, the transcription factor neurogenin 3 (Neurog3) initiates the differentiation of the beta-cells and other islet cell types from pancreatic endoderm, but the genetic program that subsequently completes this differentiation remains incompletely understood. Here we show that the transcription factor Rfx6 directs islet cell differentiation downstream of Neurog3. Mice lacking Rfx6 failed to generate any of the normal islet cell types except for pancreatic-polypeptide-producing cells. In human infants with a similar autosomal recessive syndrome of neonatal diabetes, genetic mapping and subsequent sequencing identified mutations in the human RFX6 gene. These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes.

Impact of Time of Day on Glycemia in Response to Postprandial Supramaximal Sprints in Adults With Type 1 Diabetes.

OBJECTIVES: In this study we explore the impact of postprandial exercise timing (morning vs evening) on glycemia in individuals with type 1 diabetes (T1D) during short all-out sprints on a cycle ergometer. METHODS: Ten healthy physically sedentary male (n=7) and female (n=3) volunteers with type 1 diabetes, 22.8±2.8 years of age, and with a diabetes duration of 9.7±5.5 years and glycated hemoglobin level of 8.6±1.2%, underwent comprehensive screening and assessment of their physical health and fitness status before study participation, under the guidance of a physician. Each participant underwent 2 postprandial exercise sessions on separate days: the first in the morning at 8:00 AM and second in the evening at 8:00 PM, both conducted 60 minutes after a standardized meal. RESULTS: Morning exercise showed a less pronounced reduction in plasma glucose (PG) levels compared with evening exercise (-2.01±1.24 vs -3.56±1.6 mmol/L, p=0.03). In addition, higher cortisol levels were observed in the morning vs evening (128.59±34 vs 67.79±26 ng/mL, p<0.001). CONCLUSIONS: Morning repeated sprint exercise conducted in the postprandial state consistent with the protective effect of higher cortisol levels resulted in a smaller reduction in PG levels compared with evening exercise. This highlights the potential influence of exercise timing on glycemic responses and cortisol secretion in the management of T1D.

Managing Impending Nonsevere Hypoglycemia With Oral Carbohydrates in Type 1 Diabetes: The REVERSIBLE Trial.

OBJECTIVE: Current guidelines recommend initiating treatment for nonsevere (NS) hypoglycemia with 15 g carbohydrates (CHO) at 15-min intervals when blood glucose (BG) reaches <70 mg/dL (3.9 mmol/L). Despite this recommendation, NS hypoglycemia management remains challenging for individuals living with type 1 diabetes (T1D). We aimed to assess the efficacy of 15 g CHO at higher BG levels. RESEARCH DESIGN AND METHODS: A total of 29 individuals with T1D participated in an open-label crossover study. After an inpatient subcutaneous insulin-induced decrease in BG in the fasting state, 16 g CHO was administered orally at a plasma glucose (PG) of <70 (3.9), ≤80 (4.5), or ≤90 mg/dL (5.0 mmol/L). The primary outcome was time spent in hypoglycemia (<70 mg/dL) after initial CHO intake. RESULTS: When comparing the <70 (control) with the ≤80 and ≤90 mg/dL treatment groups, 100 vs. 86 (P = 0.1201) vs. 34% (P < 0.0001) of participants reached hypoglycemia, respectively. These hypoglycemic events lasted 26.0 ± 12.6 vs. 17.9 ± 14.7 (P = 0.026) vs. 7.1 ± 11.8 min (P = 0.002), with a PG nadir of 56.57 ± 9.91 vs. 63.60 ± 7.93 (P = 0.008) vs. 73.51 ± 9.37 mg/dL (P = 0.002), respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥70 mg/dL), compared with 52% in the ≤80 mg/dL group and 31% in the ≤90 mg/dL group, with no significant rebound hyperglycemia (>180 mg/dL) within the first hour. CONCLUSIONS: For some impending NS hypoglycemia episodes, individuals with TID could benefit from CHO intake at a higher BG level.

Intersectoral health interventions to improve the well-being of people living with type 2 diabetes: a scoping review protocol.

INTRODUCTION: Intersectoral collaboration is a collaborative approach between the health sectors and other sectors to address the interdependent nature of the social determinants of health associated with chronic diseases such as diabetes. This scoping review aims to identify intersectoral health interventions implemented in primary care and community settings to improve the well-being and health of people living with type 2 diabetes. METHODS AND ANALYSIS: This protocol is developed by the Arksey and O'Malley (2005) framework for scoping reviews and the Levac et al methodological enhancement. MEDLINE, Embase, CINAHL, grey literature and the reference list of key studies will be searched to identify any study, published between 2000 and 2023, related to the concepts of intersectorality, diabetes and primary/community care. Two reviewers will independently screen all titles/abstracts, full-text studies and grey literature for inclusion and extract data. Eligible interventions will be classified by sector of action proposed by the Social Determinants of Health Map and the conceptual framework for people-centred and integrated health services and further sorted according to the actors involved. This work started in September 2023 and will take approximately 10 months to be completed. ETHICS AND DISSEMINATION: This review does not require ethical approval. The results will be disseminated through a peer-reviewed publication and presentations to stakeholders.

Efficacy of Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes Using Oral Carbohydrates During Automated Insulin Delivery With and Without Glucagon.

OBJECTIVES: Self-management guidelines for nonsevere hypoglycemia (NS-H) in type 1 diabetes recommend 15 g of simple carbohydrates (CHO) at 15-minute intervals. Because automated insulin delivery (AID) preventively reduces or suspends insulin infusion for imminent hypoglycemia, we aimed to determine whether guidelines were excessive during AID. METHODS: This work was a secondary analysis of NS-H episodes during inpatient single-hormone (insulin) or dual-hormone (insulin and glucagon) AID trials with standardized CHO treatment protocols. RESULTS: Forty NS-H episodes occurred: 15 during single-hormone arms (2 trials) and 25 during dual-hormone arms (5 trials). At NS-H treatment T0min, plasma glucose (PG) level was 3.1±0.6 mmol/L, corresponding to a sensor value of 3.6±0.6 mmol/L. Fifteen minutes after CHO consumption, PG increased by 0.9±0.8 mmol/L, recovering 45% of episodes to a safe PG of ≥4.0 mmol/L. With repeated CHO consumption, time to recovery was 21.4±15.7 minutes without rebound hyperglycemia; PG 1 hour after initial CHO was 5.9±2.0 mmol/L. Outcome differences between single-hormone and dual-hormone systems were not statistically significant, except for higher insulin and glucagon levels and less repeated treatments in dual-hormone AID. PG and glucagon levels at T0min were positively associated with increase in PG at T15min and negatively associated with time to recovery. CONCLUSIONS: NS-H self-management CHO 15-g/15-minute guidelines were neither excessive nor optimal during AID. There is a need to examine data with different AID systems to optimize treatment recommendations.

Non-severe hypoglycemia in type 1 diabetes: a randomized crossover trial comparing two quantities of oral carbohydrates at different insulin-induced hypoglycemia ranges.

Aims: Non-severe hypoglycemia (NS-H) is challenging for people living with type 1 diabetes (PWT1D) and often results from relative iatrogenic hyper-insulinemia. Current guidelines recommend a one-size-fits-all approach of 15-20 g of simple carbohydrates (CHO) every 15 min regardless of the triggering conditions of the NS-H event. We aimed to test different amounts of CHO to treat insulin-induced NS-H at various glucose ranges. Methods: This is a randomized, four-way, crossover study involving PWT1D, testing NS-H treatment outcomes with 16 g vs. 32 g CHO at two plasma glucose (PG) ranges: A: 3.0-3.5 mmol/L and B: <3.0 mmol/L. Across all study arms, participants consumed an additional 16 g of CHO if PG was still <3.0 mmol/L at 15 min and <4.0 mmol/L at 45 min post-initial treatment. Subcutaneous insulin was used in a fasting state to induce NS-H. Participants had frequent venous sampling of PG, insulin, and glucagon levels. Results: Participants (n = 32; 56% female participants) had a mean (SD) age of 46.1 (17.1) years, had HbA1c at 54.0 (6.8 mmol/mol) [7.1% (0.9%)], and had a diabetes duration of 27.5 (17.0) years; 56% were insulin pump users. We compared NS-H correction parameters between 16 g and 32 g of CHO for range A, 3.0-3.5 mmol/L (n = 32), and range B, <3.0 mmol/L (n = 29). Change in PG at 15 min for A: 0.1 (0.8) mmol/L vs. 0.6 (0.9) mmol/L, p = 0.02; and for B: 0.8 (0.9) mmol/L vs. 0.8 (1.0) mmol/L, p = 1.0. Percentage of participants with corrected episodes at 15 min: (A) 19% vs. 47%, p = 0.09; (B) 21% vs. 24%, p = 1.0. A second treatment was necessary in (A) 50% vs. 15% of participants, p = 0.001; (B) 45% vs. 34% of participants, p = 0.37. No statistically significant differences in insulin and glucagon parameters were observed. Conclusions: NS-H, in the context of hyper-insulinemia, is difficult to treat in PWT1D. Initial consumption of 32 g of CHO revealed some advantages at the 3.0-3.5 mmol/L range. This was not reproduced at lower PG ranges since participants needed additional CHO regardless of the amount of initial consumption. Clinical trial registration: ClinicalTrials.gov, identifier NCT03489967.

Anticipated Basal Insulin Reduction to Prevent Exercise-Induced Hypoglycemia in Adults and Adolescents Living with Type 1 Diabetes.

Objective: We investigated the effect of two key timings for basal insulin rate reduction on exercise-induced glucose changes and explored the association between circulating insulin concentrations and muscle vasoreactivity. Research Design and Methods: Twenty adults and adolescents performed 60-min exercise sessions (ergocycle) at 60% VO2peak, 240 min after a standardized lunch. In a randomized order, we compared an 80% basal insulin reduction applied 40 min (T-40) or 90 min (T-90) before exercise onset. Near-infrared spectroscopy was used to investigate muscle hemodynamics at vastus lateralis. Glucose and insulin plasma concentrations were measured. Results: Reduction in plasma glucose (PG) level during exercise was attenuated during T-90 versus T-40 strategy (-0.89 ± 1.89 mmol/L vs. -2.17 ± 2.49 mmol/L, respectively; P = 0.09). Linear mixed model analysis showed that PG dropped by an additional 0.01 mM per minute in T-40 versus T-90 (time × strategy interaction, P < 0.05). The absolute number of hypoglycemic events was not different between the two strategies, but they occurred later with T-90. Free insulin tends to decrease more during the pre-exercise period in the T-90 strategy (P = 0.08). Although local muscle vasodilatation (ΔTHb) was comparable between the two strategies, we found that PG dropped more in cases of higher exercise-induced skeletal muscle vasodilatation (ΔTHb × time interaction P < 0.005, e: -0.0086 mM/min and additional mM of ΔTHb). Conclusion: T-90 timing reduced exercise-induced drop in PG and delayed the occurrence of hypoglycemic episodes compared with T-40 timing without a significant reduction in the number of events requiring treatment. Trial registration: ClinicalTrials.gov identifier: NCT03349489.

Self-reported Severe and Nonsevere Hypoglycemia in Type 1 Diabetes: Population Surveillance Through the BETTER Patient Engagement Registry: Development and Baseline Characteristics.

OBJECTIVES: The BETTER (BEhaviors, Therapies, TEchnologies and hypoglycemic Risk in Type 1 diabetes) registry is a type 1 diabetes population surveillance system codeveloped with patient partners to address the burden of hypoglycemia and assess the impact of new therapies and technologies. The aim of this report was to describe the baseline characteristics of the BETTER registry cohort. METHODS: A cross-sectional baseline evaluation was performed of a Canadian clinical cohort established after distribution of an online questionnaire. Participants were recruited through clinics, public foundations, advertising and social media. As of February 2021, 1,430 persons ≥14 years of age and living with type 1 diabetes or latent-autoimmune diabetes (LADA) were enrolled. The trial was registered on ClinicalTrials.gov (NCT03720197). RESULTS: Participants were (mean ± standard deviation) 41.2±15.7 years old with a diabetes duration of 22.0±14.7 years, 62.0% female, 92.1% Caucasian and 7.8% self-reporting as LADA, with 40.9% using a continuous subcutaneous insulin infusion (CSII) system and 78.0% using a continuous glucose monitoring (CGM) system. The most recent glycated hemoglobin ≤7% was reported by 29.7% of participants. At least 1 episode of hypoglycemia <3.0 mmol/L (level 2-H) in the last month was reported by 78.4% of participants, with a median (interquartile range) of 5 (3, 10) episodes. The occurrence of severe hypoglycemia (level 3-H) in the last 12 months was reported by 13.3% of participants. Among these, the median number of episodes was 2 (1, 3). CONCLUSIONS: We have established the first surveillance registry for people living with type 1 diabetes in Canada relying on patient-reported outcomes and experiences. Hypoglycemia is a highly prevalent burden despite a relatively wide adoption of CSII and CGM use.

Minimizing the Risk of Exercise-Induced Glucose Fluctuations in People Living With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion: An Overview of Strategies.

Physical activity (PA) is important for individuals living with type 1 diabetes (T1D) due to its various health benefits. Nonetheless, maintaining adequate glycemic control around PA remains a challenge for many individuals living with T1D because of the difficulty in properly managing circulating insulin levels around PA. Although the most common problem is increased incidence of hypoglycemia during and after most types of PA, hyperglycemia can also occur. Accordingly, a large proportion of people living with T1D are sedentary partly due to the fear of PA-associated hypoglycemia. Continuous subcutaneous insulin infusion (CSII) offers a higher precision and flexibility to adjust insulin basal rates and boluses according to the individual's specific needs around PA practice. Indeed, for physically active patients with T1D, CSII can be a preferred option to facilitate glucose regulation. To our knowledge, there are no guidelines to manage exercise-induced hypoglycemia during PA, specifically for individuals living with T1D and using CSII. In this review, we highlight the current state of knowledge on exercise-related glucose variations, especially hypoglycemic risk and its underlying physiology. We also detail the current recommendations for insulin modulations according to the different PA modalities (type, intensity, duration, frequency) in individuals living with T1D using CSII.

Comparing an adiposopathy approach with four popular classifications schemes to categorize the metabolic profile of postmenopausal women.

Numerous classifications are used to discern metabolically healthy obese (MHO) from metabolically abnormal obese (MAO) individuals. The goal of this study was to compare a single phenotype approach, adiposopathy (i.e., the plasma adiponectin/leptin ratio), with four commonly used classifications (International Diabetes Federation (IDF), Karelis, Lynch, Wildman), all based on obesity with other risk factors), for their ability to discern phenotypic differences between MAO and MHO postmenopausal women. Anthropometry, body composition, blood pressure, cardiorespiratory fitness (CRF), lipid-lipoprotein, hepatic, inflammatory, and adipokine profiles, as well as glucose-insulin homeostasis, were assessed in 79 obese sedentary postmenopausal women (60 ± 5 years; body mass index, BMI, 34.0 ± 3.7 kg/m2). Abdominal subcutaneous adipose tissue (SCAT) expression of selected genes involved in fatty acid metabolism and inflammation was used as markers of tissue state (n = 48). Beyond their intrinsic criteria, adiposopathy was almost as effective as the Karelis definition in discerning differences in MHO for adiposity (reduced body weight, BMI, waist circumference, and fat mass), lipid-lipoprotein (lower triacylglycerol and higher HDL-cholesterol levels, reduced atherogenic ratios) and adipokine (higher adiponectin and lower leptin levels) profiles, and glucose-insulin homeostasis (lower insulin resistance) as well as for some SCAT gene expression related to lipolysis and lipogenesis, but was the only one able to distinguish these subjects for greater CRF. The other classifications revealed fewer differences between MAO and MHO women. These data suggest that considering a marker of AT dysfunction such as adiposopathy either alone or in addition to other criteria could be potentially interesting in discerning the MHO phenotype.