Véronique Gingras

Lifestyle and Cardiometabolic Risk in Adults with Type 1 Diabetes: A Review

Over the past decades, there has been a major upward shift in the prevalence of cardiometabolic risk (CMR) factors (central obesity, insulin resistance, hypertension and dyslipidemia) in patients with type 1 diabetes, which could have either an additive or a synergistic effect on risk for cardiovascular disease. These metabolic changes are occurring in parallel to the worldwide obesity epidemic and the widespread use of intensive insulin therapy. Poor lifestyle habits (poor diet quality, sedentary behaviours and smoking) are known to be driving factors for increased CMR factors in the general population. The objective of this review is to explore the lifestyle habits of adults with type 1 diabetes and its potential association with CMR factors. Evidence suggests that adherence to dietary guidelines is low in subjects with type 1 diabetes with a high prevalence of patients consuming an atherogenic diet. Sedentary habits are also more prevalent than in the general population, possibly because of the additional contribution of exercise-induced hypoglycemic fear. Moreover, the prevalence of smokers is still significant in the population with type 1 diabetes. All of these behaviours could trigger a cascade of metabolic anomalies that may contribute to increased CMR factors in patients with type 1 diabetes. The intensification of insulin treatment leading to new daily challenges (e.g. carbohydrates counting, increase of hypoglycemia) could contribute to the adoption of poor lifestyle habits. Preventive measures, such as identification of patients at high risk and promotion of lifestyle changes, should be encouraged. The most appropriate therapeutic measures remain to be established.

Glucagon in the 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.

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.

Predictors of cardiovascular risk among patients with type 1 diabetes: A critical analysis of the metabolic syndrome and its components

Patients with type 1 diabetes (T1D) are at increased risk for cardiovascular diseases. The metabolic syndrome (MetS), a complex disorder defined by a cluster of interconnected factors including abdominal obesity, hypertension, dyslipidaemia and insulin resistance, has been proposed to identify patients with T1D at high cardiovascular risk. The MetS has been identified in 8-45% of patients with T1D, depending on the definition and cohort studied. However, clinicians and researchers face several issues with the criteria for MetS in patients with T1D, therefore questioning its value in routine care. For example, three criteria can lead to overestimation of MetS prevalence; the impaired fasting glucose criterion is irrelevant as it is automatically fulfilled; and the widespread use of antihypertensive and lipid-lowering medications for cardiac and renal preventative purposes can contribute to overestimations of the prevalence of raised blood pressure and elevated triglycerides. In cross-sectional studies, the MetS has been associated mostly with an increased risk of microvascular complications whereas, in prospective cohorts, the predictive value of MetS for micro- and macrovascular outcomes has been inconsistent. While identifying diabetes patients at increased risk for cardiovascular complications and early mortality is crucial from a prevention standpoint, for patients with T1D, the current definition of MetS may not be the most suitable tool. The aims of the present report are to review the applicability and limitations of the MetS in patients with T1D, and to discuss alternative avenues to identify high-risk patients.

Treatment of Hypoglycemia in Adult Patients with Type 1 Diabetes: An Observational Study

OBJECTIVES 1) To characterize the nutritional treatment of hypoglycemia in adult patients with type 1 diabetes mellitus and 2) to compare the characteristics of participants who follow the recommendations with the characteristics of those who do not. METHODS A total of 121 adults with type 1 diabetes were included in this cross-sectional analysis. Participants completed a food record and a glycemia and insulin doses logbook to collect data on mild to moderate hypoglycemic events (glycemia <4.0 mmol/L or 4.0 to 5.0 mmol/L with symptoms) and their treatments over a 2-day period. Participants were identified as overcorrecting if they consumed, within 15 minutes after the episode, >20g of carbohydrates for correction. Self-administered questionnaires about fear of hypoglycemia were completed, and cardiometabolic profile variables were measured (glycated hemoglobin, blood pressure, lipid profile and body mass indexes). RESULTS Of the 121 participants, 94 (78%) reported at least 1 hypoglycemic event, for a total of 271 events (2.2±2.1 episodes per patient). Of these events, 64% were treated within 15 minutes, and they were treated primarily with fruit juice or sweet beverages (39%) or mixed snacks (29%). Average carbohydrate intake for treatment was 32±24 grams. Of the participants, 73% overtreated their episodes. They were significantly younger and had greater fear of hypoglycemia than those who treated the episodes adequately. No difference was observed for cardiometabolic variables. CONCLUSIONS The majority of patients in our cohort overtreated their hypoglycemic episodes. These results suggest that hypoglycemia-correction education needs to be reinforced.

Practices, perceptions and expectations for carbohydrate counting in patients with type 1 diabetes – Results from an online survey

AIMS Characterize adult patients with diabetes on intensive insulin therapy in terms of: (a) practices and perceived difficulties relative to carbohydrate counting (CC) and diabetes treatment, and (b) their perceptions and expectations relative to CC. METHODS Participants completed a 30-question web-based questionnaire. RESULTS Participants with type 1 diabetes (T1D) and using CC as part of their treatment plan (n=180) were included in this analysis. Participants were predominantly women (64%), aged 42±13years old and had diabetes for 22±13years. A large proportion of participants reported being confident in applying CC (78%) and considered precise CC as being important for glycemic control (91%), while only 17% reported finding CC difficult. Despite the low perceived difficulty associated with CC, many specific difficulties were encountered by patients such as the perception that glycemia fluctuates even with appropriate CC and that CC complicates the management of diabetes. A larger proportion of participants with a lower level of education (<university degree) and current or history of depression reported not feeling confident in applying CC. Most respondents believed that new technologies could facilitate CC (57%) and would be interested in such technology (62%). CONCLUSIONS Although a majority of participant reported being confident in applying CC, many difficulties and constraints associated with CC have been identified. These results highlight that patients with a lower level of education and with a history or current depression could benefit from specific CC education strategies. Future studies should examine the efficacy of technology tools to facilitate CC.

Association between post-dinner dietary intakes and nocturnal hypoglycemic risk in adult patients with type 1 diabetes

AIMS To describe (i) current bedtime nutritional practices and (ii) the association between post-dinner dietary intake and the occurrence of non-severe nocturnal hypoglycemia (NH) in real-life conditions among adult patients with type 1 diabetes using insulin analogs. METHODS One hundred adults (median [interquartile range]: age 46.4 [36.0-55.8] years, HbA1c 7.9 [7.3-8.6] % (63 [56-70] mmol/mol)) using multiple daily injections (n=67) or insulin pump (n=33) wore a blinded continuous glucose monitoring system and completed a food diary for 72-h. RESULTS NH occurred on 28% of 282 nights analyzed. (i) Patients reported post-dinner dietary intakes on 63% of the evenings. They injected rapid-acting insulin boluses on 64 occasions (23% of 282 evenings). These insulin boluses were mostly injected with (n=37) dietary intakes. (ii) Post-dinner dietary intake was not associated with NH occurrence in univariate analyses. In multivariate analyses, the injection of rapid-acting insulin modulated the association between post-dinner dietary intake and NH: with insulin, post-dinner carbohydrate intake was positively associated with NH (odds ratio (OR): 1.16 [95% confidence interval, CI: 1.04-1.29] per 5g increase, p=0.008); without insulin, post-dinner protein intake was inversely associated with NH occurrence (OR [95% CI]: 0.88 [0.78-1.00] per 2g increase, p=0.048). CONCLUSIONS NH remains frequent in adults with type 1 diabetes. There is a complex relationship between post-dinner dietary intake and NH occurrence, including the significant role of nutrient content and rapid-acting insulin injection that requires further investigation.

Impact of erroneous meal insulin bolus with dual-hormone artificial pancreas using a simplified bolus strategy - A randomized controlled trial

Postprandial glucose control remains challenging for patients with type 1 diabetes (T1D). A simplified meal bolus approach with a dual-hormone (insulin and glucagon) closed-loop system (DH-CLS) has been tested; yet, the impact of categorization errors with this strategy is unknown. The objective was to compare, in a randomized controlled inpatient trial, DH-CLS with the simplified meal bolus approach for two different meals properly categorized or overestimated. We tested, in patients with T1D, the simplified strategy with two standardized breakfasts (n = 10 per meal) adequately categorized or overestimated: (1) 75 g and (2) 45 g of carbohydrate. No difference was observed for percentage of time <4.0 mmol/L over a 4-hour post-meal period (primary outcome; median [IQR]: 0[0–0] vs. 0[0–0] for both comparisons, p = 0.47 and 0.31 for the 75 g and 45 g meals, respectively). Despite higher meal insulin boluses with overestimation for both meals (9.2 [8.2–9.6] vs. 8.1 [7.3–9.1] U and 8.4 [7.2–10.4] vs. 4.8 [3.7–5.6] U; p < 0.05), mean glycemia, percentage of time in target range and glucagon infusion did not differ. Additional scenarios were tested in silico with comparable results. These results suggest that the DH-CLS with a simplified meal bolus calculation is probably able to avoid hypoglycemia in the event of meal size misclassification.

Impact of macronutrient content of meals on postprandial glucose control in the context of closed-loop insulin delivery: A randomized cross-over study

The aim of this randomized four‐way cross‐over study was to examine the effect of added protein and/or fat in standard meals with a fixed carbohydrate content on postprandial glucose control with closed‐loop insulin delivery in adults with type 1 diabetes. Participants (n = 15) consumed breakfast meals with a fixed carbohydrate content (75 ± 1 g) and added protein and/or fat (35 ± 2 g): (1) carbohydrate‐only (standard), (2) high protein (HP), (3) high fat (HF) and (4) high fat + protein (HFHP). The closed‐loop insulin delivery algorithm generated insulin bolus and infusion rates. The addition of fat, protein or both did not impact 5‐hour post‐meal sensor glucose area under the curve (AUC) (main outcome), mean sensor glucose or glycaemic peak as compared with a standard meal (P > 0.05). However, time to glycaemic peak was delayed by 40 minutes (P = 0.03) and 5‐hour post‐meal basal insulin requirements were 39% higher (P = 0.04) with an HFHP meal compared with a standard meal. In conclusion, in the context of closed‐loop insulin delivery, protein and/or fat meal content affects the timing of postprandial glycaemic peak, insulin requirements and late glycaemic excursion, without impacting overall 5‐hour AUC.

Diabète de type 1 et surplus de poids : au-delà des glucides

Resume Une augmentation de la prevalence de surpoids et de complications cardio-metaboliques, possiblement secondaire a une faible adhesion a de saines habitudes de vie, a ete observee chez les patients atteints de diabete de type 1, ce qui pourrait majorer leur risque cardiovasculaire. Tandis que la qualite alimentaire des patients est sous-optimale, les recommandations nutritionnelles sont concentrees sur le comptage des glucides. Des etudes sont necessaires pour etablir des recommandations pour ameliorer la qualite alimentaire et la gestion du poids corporel.