A qualitative study exploring the expectations of people living with type 1 diabetes regarding prospective use of a hybrid closed-loop system.

AIM: To identify the expectations of a diversified sample of informed adults with type 1 diabetes on their prospective use of a hybrid closed-loop system. METHODS: Semi-structured interviews were conducted with 16 adults with type 1 diabetes who shared their expectations on an experimental hybrid closed-loop system after receiving information on its design, functioning and capability. The sample had equal representation of genders and diabetes management methods and was diversified according to age, education and occupation when possible. Qualitative content analysis of the interview transcripts with MaxQDA was used to identify expected benefits, expected inconveniences and concerns, expected improvements to design and functionalities, and interest and trust in the system. RESULTS: Participants expected benefits regarding diabetes management, clinical outcomes, psychosocial aspects of their lives, nutrition and meals, and physical activity. Participants expected inconveniences or shared concerns regarding wearability, costs and technical limitations. According to participants, improvements could be made to the system's physical appearance, practical convenience, functionalities, and software integration. Overall, 12 participants would use the system. While participants' trust could be immediate or grow over time, it could ultimately be conditional on the system's performance. CONCLUSION: Prospective users' general enthusiasm and trust foster the clinical and commercial success of hybrid closed-loop systems. However, poor user satisfaction caused by unrealistic expectations and plausible inconveniences and concerns may limit this success. Providing prospective users with comprehensive information while validating their understanding could mitigate unrealistic expectations. Improvements to design and coverage policies could favour uptake.

Insulin receptor-independent upregulation of cellular glucose uptake.

BACKGROUND: Cellular glucose uptake can be enhanced by upregulating Ras signaling in either insulin-dependent or -independent manner. In presence of insulin and intact insulin signaling, Ras has a negligible role in glucose uptake. Conversely, when insulin signaling is impaired in obesity or diabetes, the insulin-independent Ras pathway may be valuable for enhancing glucose disposal. We previously reported that Ad36, a human adenovirus, enhances cellular glucose uptake by upregulating the Ras/Glut4 pathway. Here, we investigated if Ad36-upregulated Ras via the insulin-independent pathway, to enhance glucose uptake. Furthermore, uncontrolled upregulation of Ras is linked with oncogenic cell transformation, if the tumor-suppressor gene p53 is also downregulated. Hence, we determined if upregulation of Ras by Ad36 would induce oncogenic cell transformation. Finally, we determined the relevance of Ad36 to insulin resistance in humans. METHODS: Insulin receptor (IR) was knocked down with small interfering RNA in 3T3-L1 adipocytes, to determine if Ad36 increases the Ras/Glut4 pathway and glucose uptake without IR-signaling. Next, the effects of Ad36 on cell transformation and p53 abundance were determined. Finally, overweight or obese women were screened for seropositivity to Ad36, as an indicator of natural Ad36 infection. Associations of Ad36 infection with adiposity and C-reactive proteins (CRPs)-two key markers of insulin resistance, and with glucose disposal, were determined. RESULTS: Unaffected by IR knock-down, Ad36 significantly increased the Ras pathway, Glut4 translocation and glucose uptake in 3T3-L1 adipocytes. Despite Ras upregulation, Ad36 did not transform 3T3-L1 cells. This may be because Ad36 significantly increased p53 protein in 3T3-L1 cells or mice adipose tissue. Ad36 seropositivity was associated with greater adiposity and CRP levels, yet a significantly higher systemic glucose disposal rate. CONCLUSIONS: Overall, the study offers Ras/Glut4 pathway as an alternate to enhance glucose disposal when insulin signaling is impaired, and, importantly, provides Ad36 as a tool to understand the modulation of that pathway.

Characterizing the profile of obese patients who are metabolically healthy.

The presence of obesity-related metabolic disturbances varies widely among obese individuals. Accordingly, a unique subset of obese individuals has been described in the medical literature, which seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as a favorable lipid, inflammation, hormonal, liver enzyme and immune profile. However, recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality. Mechanisms that could explain the favorable metabolic profile of MHO individuals are poorly understood. However, preliminary evidence suggests that differences in visceral fat accumulation, birth weight, adipose cell size and gene expression-encoding markers of adipose cell differentiation may favor the development of the MHO phenotype. Despite the uncertainty regarding the exact degree of protection related to the MHO status, identification of underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping us understand factors that predispose, delay or protect obese individuals from metabolic disturbances. Collectively, a greater understanding of the MHO individual has important implications for therapeutic decision making, the characterization of subjects in research protocols and medical education.

Comparison between several insulin sensitivity indices and metabolic risk factors in overweight and obese postmenopausal women: a MONET study.

BACKGROUND AND AIMS: The purpose of this study was to compare the relationship of several insulin sensitivity indices with cardiometabolic risk factors in overweight and obese postmenopausal women. METHODS AND RESULTS: This was a cross-sectional study involving 137 overweight and obese postmenopausal women (age: 57.7+/-4.8 yrs; body mass index: 32.4+/-4.6 kg/m(2); body fat: 38.6+/-9.2 kg). Insulin sensitivity was determined by the euglycaemic-hyperinsulinemic (EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived indices (Stumvoll, Matsuda and SI(is)) and fasting surrogate indices (HOMA, QUICKI). Cardiometabolic risk factors included: body composition and visceral fat that were measured using dual energy X-ray absorptiometry and computed tomography, respectively. Peak oxygen consumption, lower body muscle strength (using weight training equipment), physical activity energy expenditure (doubly labeled water), plasma lipids and C-reactive protein were also measured. Correlations of insulin sensitivity indices with metabolic risk factors showed some similarities, however, a wide range of variations were also observed. Furthermore, our results showed that visceral fat was the primary predictor for surrogate and OGTT indices, explaining 15-28% of the variance and the triglycerides/HDL-C ratio was the primary predictor for the EH clamp indices, explaining 15-17% of the variance. CONCLUSION: The present study indicates that the different methods of measuring and/or expressing insulin sensitivity display variations for associations with cardiometabolic risk factors. Therefore, interpretations of relationships between insulin sensitivity indices and cardiometabolic risk factors should take into account the method used to estimate and express insulin sensitivity.

A critical review and analysis of ethical issues associated with the artificial pancreas.

The artificial pancreas combines a hormone infusion pump with a continuous glucose monitoring device, supported by a dosing algorithm currently installed on the pump. It allows for dynamic infusions of insulin (and possibly other hormones such as glucagon) tailored to patient needs. For patients with type 1 diabetes the artificial pancreas has been shown to prevent more effectively hypoglycaemic events and hyperglycaemia than insulin pump therapy and has the potential to simplify care. However, the potential ethical issues associated with the upcoming integration of the artificial pancreas into clinical practice have not yet been discussed. Our objective was to identify and articulate ethical issues associated with artificial pancreas use for patients, healthcare professionals, industry and policymakers. We performed a literature review to identify clinical, psychosocial and technical issues raised by the artificial pancreas and subsequently analysed them through a common bioethics framework. We identified five sensitive domains of ethical issues. Patient confidentiality and safety can be jeopardized by the artificial pancreas' vulnerability to security breaches or unauthorized data sharing. Public and private coverage of the artificial pancreas could be cost-effective and warranted. Patient selection criteria need to ensure equitable access and sensitivity to patient-reported outcomes. Patient coaching and support by healthcare professionals or industry representatives could help foster realistic expectations in patients. Finally, the artificial pancreas increases the visibility of diabetes and could generate issues related to personal identity and patient agency. The timely consideration of these issues will optimize the technological development and clinical uptake of the artificial pancreas.

Timing of insulin basal rate reduction to reduce hypoglycemia during late post-prandial exercise in adults with type 1 diabetes using insulin pump therapy: A randomized crossover trial.

AIMS: To compare the efficacy of three timings to decrease basal insulin infusion rate to reduce exercise-induced hypoglycaemia in patients with type 1 diabetes (T1D) using pump therapy. METHODS: A single-blinded, randomized, 3-way crossover study in 22 adults that had T1D > 1 year and using insulin pump > 3 months (age, 40 ± 15 years; HbA1c, 56.3 ± 10.2 mmol/mol). Participants practiced three 45-min exercise sessions (ergocyle) at 60% VO2peak 3 hours after lunch comparing an 80% reduction of basal insulin applied 40 minutes before (T-40), 20 minutes before (T-20) or at exercise onset (T0). RESULTS: No significant difference was observed for percentage of time spent < 4.0 mmol/L (T-40: 16 ± 25%; T-20: 26 ± 27%; T0: 24 ± 29%) (main outcome) and time spent in target range 4.0-10.0 mmol/L (T-40: 63 ± 37%; T-20: 66 ± 25%; T0: 65 ± 31%). With T-40 strategy, although not significant, starting blood glucose (BG) was higher (T-40: 8.6 ± 3.6 mmol/L; T-20: 7.4 ± 2.5 mmol/L ; T0: 7.4 ± 2.7 mmol/L), fewer patients needed extra carbohydrates consumption prior to exercise for BG < 5.0 mmol/L (T-40: n = 3; T-20: n = 5; T0: n = 6) as well as during exercise for BG < 3.3 mmol/L [T-40: n = 6 (27%); T-20: n = 12 (55%); T0: n = 11 (50%)] while time to first hypoglycaemic episode was delayed (T-40: 28 ± 14 min; T-20: 24 ± 10 min; T0: 22 ± 11 min). CONCLUSION: Decreasing basal insulin infusion rate by 80% up to 40 minutes before exercise onset is insufficient to reduce exercise-induced hypoglycaemia.

Efficacy of dual-hormone artificial pancreas to alleviate the carbohydrate-counting burden of type 1 diabetes: A randomized crossover trial.

AIM: Carbohydrate-counting is a complex task for many patients with type 1 diabetes. This study examined whether an artificial pancreas, delivering insulin and glucagon based on glucose sensor readings, could alleviate the burden of carbohydrate-counting without degrading glucose control. METHODS: Twelve adults were recruited into a randomized, three-way, crossover trial (ClinicalTrials.gov identifier No. NCT01930097). Participants were admitted on three occasions from 7AM to 9PM and consumed a low-carbohydrate breakfast (women: 30g; men: 50g), a medium-carbohydrate dinner (women: 50g; men: 70g) and a high-carbohydrate lunch (women: 90g; men: 120g). At each visit, glucose levels were randomly regulated by: (1) conventional pump therapy; (2) an artificial pancreas (AP) accompanied by prandial boluses, matching the meal's carbohydrate content based on insulin-to-carbohydrate ratios (AP with carbohydrate-counting); or (3) an AP accompanied by prandial boluses based on qualitative categorization (regular or large) of meal size (AP without carbohydrate-counting). RESULTS: The AP without carbohydrate-counting achieved similar incremental AUC values compared with carbohydrate-counting after the low- (P=0.54) and medium- (P=0.38) carbohydrate meals, but yielded higher post-meal excursions after the high-carbohydrate meal (P=0.004). The AP with and without carbohydrate-counting yielded similar mean glucose levels (8.2±2.1mmol/L vs. 8.4±1.7mmol/L; P=0.52), and both strategies resulted in lower mean glucose compared with conventional pump therapy (9.6±2.0mmol/L; P=0.02 and P=0.03, respectively). CONCLUSION: The AP with qualitative categorization of meal size could alleviate the burden of carbohydrate-counting without compromising glucose control, although more categories of meal sizes are probably needed to effectively control higher-carbohydrate meals.

Effect of cysteine-rich whey protein (immunocal®) supplementation in combination with resistance training on muscle strength and lean body mass in non-frail elderly subjects: a randomized, double-blind controlled study.

OBJECTIVES: The purpose of the present study was to examine the effect of a cysteine-rich whey protein (Immunocal®) supplementation in combination with resistance training on muscle strength and lean body mass (LBM) in elderly individuals. We hypothesized that the cysteine-rich whey protein (Immunocal®) group would experience a greater increase in muscle strength and lean body mass versus the control group (casein). DESIGN: Randomized double-blind controlled intervention study. SETTING: Institut de Recherches Cliniques de Montréal in Montreal, Canada. PARTICIPANTS: Ninety-nine non-frail elderly subjects were recruited. INTERVENTION: Participants were randomly assigned into two groups. The experimental group received a cysteine-rich whey protein isolate (Immunocal®) (20 g/day) and the control group received casein (20 g/day) during a 135-day period. In addition, both groups performed the same resistance training program (3 times per week). MEASUREMENTS: Body composition (DXA) and muscle strength (leg press) were measured. RESULTS: Of the 99 recruited participants, 84 completed the 135-day study period. Of these, 67 subjects (33 in the casein group and 34 in the Immunocal® group) complied and used at least 80 % of the study product and completed at least 80 % of their training sessions. Results in this selected group show an increase in all three muscle strength variables (absolute, normalized by BW and by LBM) by 31.0 %, 30.9 % and 30.0 %, respectively in the casein group as well as 39.3 %, 39.9 % and 43.3 %, respectively in the Immunocal® group after the intervention (p < 0.05). The increases in muscle strength favored Immunocal® versus casein by approximately 10 % when expressed in kg per kg BW and in kg per kg LBM (p < 0.05). No significant changes were found between pre-and-post intervention in both groups for total LBM. CONCLUSIONS: Our findings showed increases in muscle strength in both groups after resistance training, however, significant additional increases were observed in muscle strength with the addition of a cysteine-rich whey protein (Immunocal®) versus casein.

Post-breakfast closed-loop glucose control is improved when accompanied with carbohydrate-matching bolus compared to weight-dependent bolus.

AIM: We compared post-breakfast closed-loop glucose control either matched with a carbohydrate-matching bolus or a weight-dependent bolus. METHODS: Twelve adults with type 1 diabetes consumed a 75 g CHO breakfast on two occasions. In random order, the breakfast was accompanied by a full carbohydrate-matching insulin bolus (8.30 U [7.50 U-11.50 U]) or a partial weight-dependent insulin bolus (0.047 U/kg; 3.45 U [2.95 U-3.75 U]). Postprandial glucose was regulated by sensor-responsive insulin and glucagon delivery. RESULTS: Glucose control after the weight-dependent bolus was safe and feasible (glucose values returned to pre-prandial levels after 5 h). However, 5-hr incremental area under the curve and percentage of time above 10 mmol/L were lower after the full bolus compared to the partial bolus (IAUC, 2.1 [0.8-4.2] mmol/L/hr vs 8.3 [6.5-11.4] mmol/L/hr; time in hyperglycaemia, 24% [6%-29%] vs 50% [25%-63%]; P < 0.001). CONCLUSIONS: Post-breakfast closed-loop glucose control without carbohydrate counting, but based on weight-dependent bolus is feasible but a carbohydrate-matching bolus provides better glucose control. CLINICAL TRIAL REGISTRY: NCT01519102.

Evaluation of two new surrogate indices including parameters not using insulin to assess insulin sensitivity/resistance in non-diabetic postmenopausal women: a MONET group study.

AIM: The study evaluated and compared, with other surrogate indices of insulin sensitivity/resistance (IS/R), the relevance of the TyG index, a product of fasting glucose and triglyceride (TG) levels, and the EGIR index, which includes TG, high-density lipoprotein cholesterol (HDL-c) and waist circumference in its formula to estimate IS/R, in non-diabetic postmenopausal women. METHODS: A secondary analysis was performed using the baseline data for 163 non-diabetic postmenopausal women from the Montreal-Ottawa New Emerging Team (MONET) population database. The subjects participated in hyperinsulinaemic-euglycaemic (HIEG) clamp and oral glucose tolerance (OGTT) tests. Correlations and comparisons between surrogate indices were performed in addition to inter-rater agreement tests. The optimal value of surrogate indices for diagnosis of IS/R was established on a receiver operating characteristic (ROC) scatter plot. RESULTS: A significant correlation was found between the HIEG clamp and all IS/R surrogate indices tested [r=-0.370 (TyG index) to 0.608 (SIisOGTT index); P<0.001]. On ROC curve analysis, a higher AUROC was found for SIisOGTT (0.791) than for TyG and EGIR (0.706 and 0.675, respectively; P=0.07 and P<0.05, respectively). CONCLUSION: The TyG and EGIR IS/R indices were only relatively modestly related to the HIEG clamp. In contrast, both fasting- and OGTT-derived IS/R surrogate indices, which include insulin values in their formulae, appeared to be more accurate in estimating IS/R in our study population. Thus, the TyG and EGIR IS/R indices need to be tested and validated more extensively in different populations before being put to large-scale clinical use.

Seroprevalence of seven zoonotic infections in Nunavik, Quebec (Canada).

In Nunavik, common practices and food habits such as consumption of raw meat and untreated water place the Inuit at risk for contracting zoonotic diseases. The aim of this study was to determine the seroprevalence of seven zoonotic infections among the permanent residents of Nunavik. The study was conducted in the fall 2004 as part of the Nunavik Health Survey. Blood samples from adults aged 18-74 years (n = 917) were collected and analysed for the presence of antibodies against Trichinella spp., Toxocara canis, Echinococcus granulosus, Brucella spp., Coxiella burnetii, Leptospira spp. and Francisella tularensis. Information on sociodemographic characteristics, traditional activities, drinking water supply and nutrition was gathered using english/inuktitut bilingual questionnaires. The chi-squared test was used to evaluate associations between seropositivity and other measured variables. Statistically significant variables were included in a multivariate logistic regression model to control for confounding factors. Estimated seroprevalences were 8.3% for E. granulosus, 3.9% for T. canis, 5.9% for Leptospira spp. and 18.9% for F. tularensis. Seroprevalence was ≤ 1% for Trichinella spiralis, Brucella spp. and C. burnetii. For most infections, seropositivity tended to increase with age. In multivariate analyses, seroprevalence was positively (i.e. directly) associated with age and residence in the Ungava coast area for F. tularensis; age and residence in the Hudson coast area for T. canis; female gender, lower level of schooling and frequent cleaning of water reservoirs for E. granulosus. No risk factor for Leptospira spp. infection was identified. No associations were detected with regards to food habits or environmental exposures. A small but significant portion of the Nunavik population has serologic evidence of exposure to at least one of the pathogenic microorganisms investigated. Further studies are needed to better understand the mechanisms for transmission of zoonotic infections and their potential reservoirs in Nunavik.

Anthropometric, metabolic, dietary and psychosocial profiles of underreporters of energy intake: a doubly labeled water study among overweight/obese postmenopausal women--a Montreal Ottawa New Emerging Team study.

BACKGROUND/OBJECTIVES: To analyze the anthropometric, metabolic, psychosocial and dietary profiles of underreporters, identified by the doubly labeled water technique, in a well-characterized population of overweight and obese postmenopausal women. SUBJECTS/METHODS: The study population consisted of 87 overweight and obese sedentary postmenopausal women (age: 57.7+/-4.8 years, body mass index: 32.4+/-4.6 kg/m(2)). Subjects were identified as underreporters based on the energy intake to energy expenditure ratio of <0.80. We measured (1) body composition (by dual-energy X-ray absorptiometry), (2) visceral fat (by computed tomography), (3) blood profile, (4) resting blood pressure, (5) peak oxygen consumption (VO(2 peak)), (6) total energy expenditure, (7) muscle strength and (8) psychosocial and dietary profiles. RESULTS: Out of 87 subjects, 50 (57.5%) were identified as underreporting subjects in our cohort. Underreporters showed higher levels of body mass index, fat mass, visceral fat, hsC-reactive protein, perceived stress and percentage of energy from protein, as well as lower levels of VO(2 peak), dietary intake of calcium, fiber, iron, vitamin B-1 and 6, as well as servings of fruit and vegetables. Logistic regression analysis showed that fat mass, odd ratio 1.068 (95% confidence interval 1.009-1.130) and perceived stress, odd ratio 1.084 (95% confidence interval 1.011-1.162) were independent characteristics of underreporters. CONCLUSIONS: Results from this study show significant differences in anthropometric, metabolic, psychosocial and dietary profiles between underreporters and non-underreporters in our cohort of overweight and obese postmenopausal women.

Seroprevalence of Toxoplasma gondii among Nunavik Inuit (Canada).

As a result of their intimate contact with the land and their nutritional habits, the Inuit of Nunavik are considered to be at risk from zoonotic infections. To better understand the risk factors for Toxoplasma gondii infection, a serosurvey was conducted in Nunavik, Québec, in September 2004. A representative sample of the Inuit adult population of Nunavik participated in this cross-sectional study (n = 917). Antibodies (IgG) against T. gondii were detected by immunoassay. Information on sociodemographic characteristics, traditional activities, domestic environment and nutrition was gathered by questionnaire and explored as variables explanatory of seropositive results. Associations found to be statistically significant in univariate analyses were assessed by multivariable logistic regression to control for confounding factors. Almost two thirds (59.8%) of the Inuit of Nunavik were found to be seropositive for T. gondii. In multivariate analyses, risk factors for seropositivity were: increasing age, gender (women > men), lower level of education, consumption of potentially contaminated water (determined by an index of risk from waterborne infections), frequent cleaning of water reservoirs, and consumption of seal meat and feathered game. There was some variation in seroprevalence between the Ungava Bay coast (52.3%) and the Hudson Bay coast (65.6%), the two main regions of Nunavik, but this variation was not significant in the multivariable logistic regression model. This cross-sectional study demonstrated high T. gondii seroprevalence in the Inuit population and revealed that age, gender, schooling and community of residence all influence serostatus in this population. Variables related to drinking water and food choices may also influence the risk of infection. These results raise important questions about T. gondii transmission in Nunavik including possible links between terrestrial and marine cycles.