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.

Physical Activity in Pediatric Inflammatory Bowel Disease: A Scoping Review.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, systemic condition affecting the gastrointestinal tract. IBD can be severe and are associated with impairment in growth, school absences, abdominal pain, and fatigue. Physical activity (PA) could have an anti-inflammatory effect in addition to other benefits. It is important to address the possible risks, physiological effects of PA, and potential barriers, and facilitators for PA participation in pediatric IBD. However, potential barriers and facilitators to PA have yet to be adequately described. METHODS: We conducted a scoping review to map and describe the current literature on PA in pediatric IBD populations between 1980 and April 2022 using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for Scoping reviews. RESULTS: Nineteen articles were identified including 10 descriptive, 6 interventional, and 3 physiological responses to PA studies. Patients and healthy controls demonstrated similar responses to exercise. Barriers to participation were low self-esteem, body image, and active IBD symptoms. Facilitators included personal interest, activity with friends, and support from family. CONCLUSION: This review highlighted that PA participation may reduce in children with IBD-related symptoms. Short- and medium-term impacts of PA on immune modulation require further study; it is possible that regular PA does not negatively affect biomarkers of disease activity.

Gender differences in reported frequency and consequences of hypoglycemia among adults living with type 1 diabetes: Results from the BETTER registry.

AIMS: To evaluate the frequency and consequences of level 2 (L2H, glucose level < 3.0 mmol/L with autonomous management) and level 3 hypoglycemia (L3H requiring external assistance to treat), in adults living with type 1 diabetes (T1D), while investigating the role of gender. METHODS: Cross-sectional analysis of self-reported retrospective data from a Canadian registry of 900 adults living with T1D using logistic regression models adjusted for age, T1D management modalities, hypoglycemia history, and validated patient-reported outcomes scales. Changes in diabetes management, seeking healthcare resources, and impacts on daily well-being were explored. RESULTS: Of the 900 adults (66% women, mean age 43.7 ± 14.8 years, mean T1D duration 25.5 ± 14.6 years), 87% used wearable diabetes technology. L3H in the past year was reported by 15% participants, similar between genders. Women reported more L2H than men (median (Q1, Q3): 4 (2, 10) vs 3 (1,8), p = 0.015), and were more likely to report persistent fatigue after both L2H and L3H (Odds ratio [95% confidence interval]: 1.95 [1.16, 3.28] and 1.86 [1.25, 2.75], respectively) and anxiety (1.70 [1.05, 2.75]) after a L3H. CONCLUSIONS: The findings suggest taking a gender-based differential approach when addressing hypoglycemia and its various consequences for people living with T1D.

Cardiovascular Risk Factors and Adherence to Cardiovascular Protection Practice Guidelines in Adults With Type 1 Diabetes: A BETTER Registry Cross-sectional Analysis.

OBJECTIVES: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in people with type 1 diabetes (PWT1D). We assessed cardiovascular risk factors and pharmacologic treatment in a large Canadian cohort of PWT1D. METHODS: This cross-sectional study used data from adult PWT1D in the BETTER registry (n=974). CVD risk factor status, diabetes complications, and treatments (used as proxy for blood pressure and dyslipidemia) were self-reported through online questionnaires. Objective data were available for a subgroup of PWT1D (23%, n=224). RESULTS: Participants were adults (43.9±14.8 years) with a diabetes duration of 23.3±15.2 years; 34.8% reported glycated hemoglobin (A1C) levels of ≤7%, 67.2% reported a very high cardiovascular risk, and 27.2% reported at least 3 CVD risk factors. Most participants received care for CVD in accordance with the Diabetes Canada Clinical Practice Guidelines (DC-CPG), with a median recommended pharmacologic treatment score of 75.0%. However, 3 subgroups of participants with lower adherence (<70%) to DC-CPG were identified: 1) those with microvascular complications and receiving a statin (60.8%, 208 of 342) or renin-angiotensin axis nephroprotective therapy (52.6%, 180 of 342); 2) those aged ≥40 years and receiving statin therapy (67.1%, 369 of 550); and 3) those aged ≥30 years with a diabetes duration of ≥15 years and receiving statin therapy (58.9%, 344 of 584). Among a subgroup of participants with recent laboratory results, only 24.5% of PWT1D (26 of 106) achieved both A1C and low-density lipoprotein cholesterol targets. CONCLUSIONS: Most PWT1D received recommended pharmacologic cardiovascular protection, but specific subgroups required special attention. Target achievement for key risk factors remains suboptimal.

Impact of Smoking on Functional Prognosis after Ischemic Stroke according to Deprivation: A Prospective Cohort Study.

BACKGROUND: Smoking influence on poststroke prognosis remains controversial. These conflicting results could be due to some residual confounding factors not fully considered in previous studies, including social deprivation. This study aimed to assess the joint impact of deprivation and smoking on functional outcomes after ischemic stroke. METHODS: Between 2011 and 2014, 1,573 patients with a first-ever stroke were prospectively included in the French multicenter INDIA ("Inegalites sociales et pronostic des accidents vasculaires cerebraux à Dijon et Antilles-Guyane") cohort study. Patients with ischemic stroke and available data on smoking, deprivation, and outcome were considered for the analysis (n = 1,242). Deprivation was assessed using the EPICES "Evaluation de la Précarité et des Inégalites de santé dans les Centres d'Examen de Santé" score. Primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) score at 12 months. Association between smoking and moderate to severe disability (mRS score ≥3) was evaluated with logistic regression model. Interactions between smoking and deprivation were tested. RESULTS: Smokers (n = 189, 15.2%) were younger and more often deprived (EPICES score ≥30.17) than nonsmokers. A significant interaction was found between smoking status and deprivation on disability (p = 0.003). In nondeprived patients, the odds of moderate to severe disability at 12 months were twice as high in smokers as in nonsmokers (adjusted OR = 2.08, 95% CI: 1.04-4.18). This association was not observed in deprived patients (adjusted OR = 0.89, 95% CI: 0.49-1.61). CONCLUSION: The effect of smoking on functional prognosis after ischemic stroke varied according to deprivation status, with poorer outcomes observed in nondeprived patients.

Does Universal Screening for Gestational Diabetes Mellitus Improve Neonatal Outcomes in a Socially Vulnerable Population: A Prospective Study in French Guiana.

Aims/Introduction: French Guiana has a high prevalence of metabolic diseases, which are risk factors for gestational diabetes mellitus. Despite routine screening for gestational diabetes, treatment is still challenging because of health inequalities and different cultural representations of disease and pregnancy. This study was conducted to assess the role of early and universal GDM screening on obstetrical and neonatal complications in a socially deprived population. Materials and Methods: A prospective study was conducted, in the level III maternity in French Guiana. Of 2136 deliveries, 223 had gestational diabetes mellitus, 110 of whom were followed-up for 6 month to detail their social and laboratory parameters. Results: The prevalence of gestational diabetes in French Guiana (Cayenne Hospital) was estimated at 10.3%. The study population was very precarious with 70% of patients on welfare (universal health coverage or state medical assistance). The following obstetrical complications were observed: cesarean delivery (32%), history of miscarriage (26%) and preeclampsia (7.4%). Nevertheless, neonatal complications were rarely present and included hypoglycemia (2.8%) and macrosomia (2.8%). Conclusion: In French Guiana, gestational diabetes mellitus is very common. However, in a context of widespread poverty and diverse cultural representations, universal screening and monitoring limited the risk of macrosomia.

Prescription of Physical Activity by General Practitioners in Type 2 Diabetes: Practice and Barriers in French Guiana.

Background: General practitioners (GPs) are the major primary healthcare players in the management of type 2 diabetes. In addition to a well-balanced diet, physical activity (PA) appears as a necessary non-medicinal therapy in the management of diabetic patients. However, GPs emphasize several obstacles to its prescription. The aim of this study is to evaluate the practices, barriers, and factors favoring the prescription of PA in type 2 diabetic patients by GPs in French Guiana. Method: We conducted a cross-sectional descriptive study using a questionnaire, designed to interview 152 French Guiana GPs and describe their practice in prescribing PA in type 2 diabetic patients. Results: Our results revealed that the prescription of PA as a non-medicinal therapeutic choice in the management of type 2 diabetes was practiced by 74% of the French Guiana GPs. However, only 37% of GPs responded that they implemented the recommendations; indeed, only one-third knew about them. The majority of GPs were interested in PA training, but only 11% were actually trained in this practice. The lack of structure adapted to the practice of PA and the lack of awareness of the benefits of PA in metabolic pathology appeared as the main obstacles to PA prescription. Conclusion: This study highlights the importance of improving the training of GPs in the prescription of PA, the development of adapted PA structures, and collaboration between the different actors within the framework of the sport-health system in type 2 diabetes in French Guiana.

Social deprivation and 1-year survival after stroke: a prospective cohort study.

BACKGROUND: Social deprivation may have a deleterious influence on post-stroke outcomes, but available data in the literature are mixed. AIM: The aim of this cohort study was to evaluate the impact of social deprivation on 1-year survival in patients with first-ever stroke. METHODS: Social deprivation was assessed at individual level with the EPICES score, a validated multidimensional questionnaire, in 1312 patients with ischemic stroke and 228 patients with spontaneous intracerebral hemorrhage, who were prospectively enrolled in six French study centers. Baseline characteristics including stroke severity and pre-stroke functional status were collected. Multivariable Cox models were generated to evaluate the associations between social deprivation and survival at 12 months in ischemic stroke and intracerebral hemorrhage separately. RESULTS: A total of 819 patients (53.2%) were socially deprived (EPICES score ≥ 30.17). In ischemic stroke, mortality at 12 months was higher in deprived than in non-deprived patients (16% vs. 11%, p = 0.006). In multivariable analyses, there was no association between deprivation and death occurring within the first 90 days following ischemic stroke (adjusted hazard ratio [aHR] 0.81, 95% CI 0.54-1.22, p = 0.32). In contrast, an excess in mortality was observed between 90 days and 12 months in deprived compared with non-deprived patients (aHR 1.97, 95% CI 1.14-3.42, p = 0.016). In patients with intracerebral hemorrhage, mortality at 12 months did not significantly differ according to deprivation status. CONCLUSIONS: Social deprivation was associated with delayed mortality in ischemic stroke patients only and, although the exact underlying mechanisms are still to be identified, our findings suggest that deprived patients in particular may benefit from an optimization of post-stroke care.

Social deprivation among socio-economic contrasted french areas: Using item response theory analysis to assess differential item functioning of the EPICES questionnaire in stroke patients.

BACKGROUND: Multiple approaches have been proposed to measure low socio-economic status. In France the concept of precariousness, akin to social deprivation, was developed and is widely used. EPICES is a short questionnaire that was developed to measure this concept. This study aimed to evaluate Differential Item Functioning (DIF) in the EPICES questionnaire between contrasted areas: mainland France, French West Indies (FWI) and French Guiana (FG). METHODS: The population was taken from the INDIA study, which aimed to evaluate the impact of social inequalities on stroke characteristics and prognosis. Eligible people were patients referred to neurology or emergency departments for a suspicion of stroke. We assessed the DIF using hybrid ordinal logistic regression method, derived from item response theory. RESULTS: We analysed 1 553 stroke patients, including 768 from FWI (49.5%), 289 from FG (18.6%) and 496 from mainland (31.9%). We identified five items with a moderate to large DIF in area comparisons: "meeting with a social worker", "complementary health insurance", "home-owning", "financial difficulties" and "sport activities". Correlation between EPICES score and the latent variable was strong (r = 0.84). CONCLUSION: This is the first attempt to assess the DIF of the EPICES score between different French populations. We found several items with DIF, which can be explained by individual interpretation or local context. However, the DIFs did not lead to a large difference between the latent variable and the EPICES score, which indicates that it can be used to assess precariousness and social deprivation between contrasted areas.

Lipid profiles in French West Indies sickle cell disease cohorts, and their general population.

BACKGROUND: The pathophysiology of sickle cell disease (SCD) and the variability of its clinical expression remain not fully understood, whether within or between different SCD genotypes. Recent studies have reported associations between lipid levels and several SCD complications. If lipid levels have been previously described as low in sickle cell anemia (SCA), few data have been provided for sickle cell SC disease (SCC). We designed our epidemiological study to isolate lipid levels and profiles by genotype in Guadeloupian cohorts of SCA and SCC adult patients, at steady state. We compared SCD lipid levels with those of the Guadeloupian general population (GGP), and analyzed potential associations between lipid levels and SCD complications (vaso-occlusive crises, acute chest syndrome and osteonecrosis). METHODS: Lipids, apolipoproteins, biological variables and anthropometric evaluation, were collected at steady state from medical files for 62 SCC and 97 SCA adult patients. Clinical SCD complications were collected from the clinical files. Analysis was conducted by genotype for all variables. RESULTS: Different SCC and SCA lipid profiles, both distinct from their GGP's, were identified. Compared to SCC and GGP, higher triglyceride (TG) levels were observed in SCA patients, independent of hydroxyurea, hemolysis, gender, age, body mass index (BMI), abdominal obesity and clinical nutritional status. Our survey highlights also subsequent anthropometrical phenotypes, with an over-representation of abdominal obesity with normal BMI in SCA patients, and affecting almost exclusively females in both genotypes. Moreover, more frequent positive history of acute chest syndrome (ACS) was observed in SCA patients with TG level higher than 1.50 g/l, and of osteonecrosis in SCC patients having non high-density lipoprotein-cholesterol level (Non HDL-C) higher than 1.30 g/l. CONCLUSIONS: This study reveals that SCA and SCC patients exhibit distinct lipid profiles and suggests that high TG and Non HDL-C levels are associated with past histories of ACS and osteonecrosis in SCA and SCC patients, respectively.

Differences of microparticle patterns between sickle cell anemia and hemoglobin SC patients.

Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a highly variable clinical course. Although high levels of microparticles (MPs) have been consistently reported in SCA and evidence of their harmful impact on the SCA complication occurrences have been provided, no data on MP pattern in HbSC patients has been reported so far. In this study, we determined and compared the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow cytometry. Most of circulating MPs were derived from platelets (PLTs) and red blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC patients exhibited lower blood concentration of total MPs compared to SCA patients, resulting mainly from a decrease of MP levels originated from RBCs and to a lesser extent from PLTs. We did not detect any association between blood MP concentrations and the occurrence of painful vaso-occlusive crises, acute chest syndrome and pulmonary hypertension in both patient groups. We also demonstrated for the first time, that whatever the considered genotype, RBC-derived MPs exhibited higher externalized phosphatidylserine level and were larger than PLT-derived MPs.

Exacerbation of oxidative stress during sickle vaso-occlusive crisis is associated with decreased anti-band 3 autoantibodies rate and increased red blood cell-derived microparticle level: a prospective study.

Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.

CAREST--Multilingual Regional Integration for Health Promotion and Research on Sickle Cell Disease and Thalassemia.

Sickle cell disease (SCD) is a significant problem in the Caribbean, where many individuals have African and Asian forebears. However, reliable prevalence data and specific health care programs for SCD are often missing in this region. Closer collaboration between Caribbean territories initiated in 2006 to set up strategies to promote better equity in the health care system for SCD patients led to the formation of CAREST: the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. We present the effectiveness of collaborations established by CAREST to promote SCD newborn screening programs and early childhood care, to facilitate health worker training and approaches for prevention and treatment of SCD complications, and to carry out inter-Caribbean research studies.

Is there a relationship between the hematocrit-to-viscosity ratio and microvascular oxygenation in brain and muscle?

The hematocrit-to-viscosity ratio (HVR) has been widely used has an estimate of red blood cell (RBC) oxygen transport effectiveness into the microvasculature or as an oxygen delivery index. However, no study investigated the possibility of HVR to truly reflect RBC oxygen transport effectiveness or to be an oxygen delivery index. We measured blood viscosity at high shear rate (225 s(-1)), hematocrit, HVR, as well as the microvascular oxyhemoglobin saturation (TOI; tissue oxygen index) by spatial resolved near-infrared spectroscopy (NIRS) at cerebral and muscle levels in three population known to have various degrees of hemorheological abnormalities: healthy subjects (AA), patients with sickle cell SC disease (SC) characterized by moderate anemia and patients with sickle cell anemia (SS) marked by severe anemia. At both the cerebral and muscle level, HVR was positively correlated with TOI (r=0.28; p=0.03 and r=0.38; p=0.003, at the cerebral and muscle level, respectively). These findings suggest that HVR probably play a key role in blood flow and hemodynamic regulation in the microvasculature, hence modulating the amount of oxygen available for tissues. Nevertheless, the strengths of the associations are weak (R2<0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.

Relationships between systemic vascular resistance, blood rheology and nitric oxide in children with sickle cell anemia or sickle cell-hemoglobin C disease.

Vascular function has been found to be impaired in patients with sickle cell disease (SCD). The present study investigated the determinants of systemic vascular resistance in two main SCD syndromes in children: sickle cell anemia (SCA) and sickle cell-hemoglobin C disease (SCC). Nitric oxide metabolites (NOx), hematological, hemorheological, and hemodynamical parameters were investigated in 61 children with SCA and 49 children with SCC. While mean arterial pressure was not different between SCA and SCC children, systemic vascular resistance (SVR) was greater in SCC children. Although SVR and blood viscosity (ηb) were not correlated in SCC children, the increase of ηb (+18%) in SCC children compared to SCA children results in a greater mean SVR in this former group. SVR was positively correlated with ηb, hemoglobin (Hb) level and RBC deformability, and negatively with NOx level in SCA children. Multivariate linear regression model showed that both NOx and Hb levels were independently associated with SVR in SCA children. In SCC children, only NOx level was associated with SVR. In conclusion, vascular function of SCC children seems to better cope with higher ηb compared to SCA children. Since the occurrence of vaso-occlusive like complications are less frequent in SCC than in SCA children, this finding suggests a pathophysiological link between the vascular function alteration and these clinical manifestations. In addition, our results suggested that nitric oxide metabolism plays a key role in the regulation of SVR, both in SCA and SCC.

Alpha thalassemia protects sickle cell anemia patients from macro-albuminuria through its effects on red blood cell rheological properties.

While chronic hemolysis has been suspected to be involved in the development of glomerulopathy in patients with sickle cell anemia (SCA), no study focused on the implications of blood rheology. Ninety-six adults with SCA at steady state were included in the present cross-sectional study. Three categories were defined: normo-albuminuria (NORMO, n = 41), micro-albuminuria (MICRO, n = 23) and macro-albuminuria (MACRO, n = 32). Blood was sampled to measure hematological and hemorheological parameters, and genomic DNA extraction was performed to detect the presence of α-thalassemia. The prevalence of α-thalassemia was lower in the MACRO group compared with the two other groups. Anemia was more severe in the MACRO compared with the NORMO group leading the former group to exhibit decreased blood viscosity. Red blood cell deformability was lower and red blood cell aggregates strength was greater in the MACRO compared to the two other groups, and this was directly attributed to the lower frequency of α-thalassemia in the former group. Our results show the protective role of α-thalassemia against the development of sickle cell glomerulopathy, and strongly suggest that this protection is mediated through the decrease of anemia, the increase of RBC deformability and the lowering of the RBC aggregates strength.

Decreased hematocrit-to-viscosity ratio and increased lactate dehydrogenase level in patients with sickle cell anemia and recurrent leg ulcers.

Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+)--with no leg ulcers at the time of the study--were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role.