Relationship Between Risk Factors and Mortality in Type 1 Diabetic Patients in Europe: The EURODIAB Prospective Complications Study (PCS)

OBJECTIVE—The purpose of this study was to examine risk factors for mortality in patients with type 1 diabetes

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Climate change, ecosystems and smallholder agriculture in Central America: an introduction to the special issue

Central America is one of the regions most exposed to climate change (Giorgi 2006). A narrow isthmus between the Pacific Ocean and the Caribbean Sea, it is strongly affected by droughts, hurricanes and the El Niño-southern oscillation (ENSO) phenomena (CEPAL 2011). As a result, three countries in the region rank in the top 10 of the Global Climate Risk Index (Kreft and Eckstien 2013) based on the impacts of extreme weather events between 1993 and 2012.Much of the regional economy is based on agriculture. In Guatemala, Honduras and Nicaragua, more than two thirds of the population depends on agriculture. This agricultural base is often intimately tied to ecosystems, especially in diverse farming systems of smallholders. But it is increasingly threatened by climate variability and change (Bouroncle et al. 2016; Baca et al. 2014), which are inducing changes in areas suitable for crops and leading to high yield variability. Storms, floods and droughts have had the greatest impacts on agriculture in Central America over the last century (Guha-Sapir et al. 2014). This special issue addresses the adaptation challenges facing smallholders, ecosystems and ecosystem services in the region. In this introduction, we review the literature on regional climate and its drivers, climate change projections, impacts on agriculture and ecosystems, and information management for adaptation in the region. Short descriptions of the special issue contributions are provided throughout the text.Universidad de Costa Rica/[805-B6-143]/UCR/Costa RicaUniversidad de Costa Rica/[805-A9-532]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-227]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-065]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-810]/UCR/Costa RicaUniversidad de Costa Rica/[805-A4-906]/UCR/Costa RicaUniversidad de Costa Rica/[805-B6-143]/UCR/Costa RicaUniversidad de Costa Rica/[805-A9-532]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-227]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-065]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-810]/UCR/Costa RicaUniversidad de Costa Rica/[805-A4-906]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de FísicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigación en Ciencias del Mar y Limnología (CIMAR

Serum high-mobility group box-1 levels are positively associated with micro- and macroalbuminuria but not with cardiovascular disease in type 1 diabetes: the EURODIAB Prospective Complications Study.

CONTEXT AND OBJECTIVE: High-mobility group box-1 (HMGB1) is a pro-inflammatory cytokine that may contribute to the pathogenesis of micro- and macrovascular complications commonly observed in diabetes. We investigated whether HMGB1 is associated with: i) markers of low-grade inflammation (LGI) and endothelial dysfunction (ED) and pulse pressure (PP, a marker of arterial stiffness); ii) prevalent nephropathy, retinopathy and cardiovascular disease (CVD) in type 1 diabetes; and iii) the potential mediating roles of LGI, ED and PP therein. DESIGN AND METHODS: This was a cross-sectional nested case-control study of 463 patients (226 women; mean age 40±10 years) with type 1 diabetes from the EURODIAB Prospective Complications Study. We used linear and binary or multinomial logistic regression analyses adjusted for traditional risk factors. RESULTS: Serum Ln-HMGB1 levels were positively associated with LGI and ED (standardised β=0.07 (95% confidence interval (CI): 0.02-0.12) and β=0.08 (95% CI: 0.02-0.14) respectively), but not with PP. Higher Ln-HMGB1 (per unit) was associated with greater odds of micro- and macroalbuminuria: odds ratio (OR)=1.24 (95% CI: 0.90-1.71) and OR=1.61 (95% CI: 1.15-2.25) respectively, P for trend=0.004. Further adjustments for LGI or ED did not attenuate these associations. No such associations were found between Ln-HMGB1 and estimated glomerular filtration rate (eGFR), retinopathy or CVD, however. CONCLUSIONS: In type 1 diabetes, higher serum HMGB1 levels are associated with greater prevalence and severity of albuminuria, though not with eGFR, retinopathy and CVD. Prospective studies are needed to clarify the causal role of HMGB1, if any, in the pathogenesis of vascular complications in type 1 diabetes

Serum high-mobility group box-1 levels are positively associated with micro- and macroalbuminuria but not with cardiovascular disease in type 1 diabetes: the EURODIAB Prospective Complications Study

High-mobility group box-1 (HMGB1) is a pro-inflammatory cytokine that may contribute to the pathogenesis of micro- and macrovascular complications commonly observed in diabetes. We investigated whether HMGB1 is associated with: i) markers of low-grade inflammation (LGI) and endothelial dysfunction (ED) and pulse pressure (PP, a marker of arterial stiffness); ii) prevalent nephropathy, retinopathy and cardiovascular disease (CVD) in type 1 diabetes; and iii) the potential mediating roles of LGI, ED and PP therein

THE RELATIONSHIP BETWEEN SMOKING AND MICROVASCULAR COMPLICATIONS IN THE EURODIAB IDDM COMPLICATIONS STUDY

OBJECTIVE: To examine the relationship between smoking and both glycemic control and microvascular complications in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: This was a prevalence survey of 3,250 men and women aged 15-60 years with IDDM from 31 diabetes centers in 16 European countries. Participants completed a questionnaire, had retinal photographs taken, and performed a 24-h urine collection. HbA1c, frequency of hypoglycemic and ketoacidotic episodes, urinary albumin excretion rates, and retinopathy were compared by smoking category. RESULTS: The prevalence of smoking was 35% in men and 29% in women. Current smokers had poorer glycemic control and, among men, were more likely to have had a ketoacidotic episode than were those who never smoked. Ex-smokers had equivalent glycemic control and marginally more hypoglycemic episodes did than those who never smoked. Current smokers had a higher prevalence of microalbuminuria and total retinopathy than did those who never smoked. Ex-smokers had a higher prevalence of macroalbuminuria and proliferative retinopathy than did those who never smoked, but both had a similar prevalence of microalbuminuria. Adjustment for either current or long-term glycemic control could not fully account for these differences. CONCLUSIONS: Smoking is associated with poorer glycemic control and an increased prevalence of microvascular complications compared with not smoking. Ex-smokers can achieve glycemic control equivalent to and have a prevalence of early complications similar to that of those who never smoked. We suggest that poorer glycemic control can account for some of the increased risk of complications in smokers, and that quitting smoking would be effective in reducing the incidence of complications. Urgent action is required to reduce the high smoking rates in people with IDDM

Cardiovascular disease and its risk factors in IDDM in Europe

OBJECTIVE - To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS - The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean +/- SD duration of diabetes was 14.7 +/- 9.3 years. RESULTS - The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15-29 years old to 25% in patients 45-59 years old) and with duration of diabetes. The between-center variation for the whole population was from ? to 19%. In both sexes, Easting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration oi diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA(1c) level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA(1c), prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS - The overall prevalence of CVD in these IDDM patients was similar to 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations

BLOOD-PRESSURE, RETINOPATHY AND URINARY ALBUMIN EXCRETION IN IDDM - THE EURODIAB IDDM COMPLICATIONS STUDY

Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46%) and without (54%) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal (<20 mu g/min) below median diastolic pressure (75 mmHg) and increased steeply (p < 0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk

Nutritional intake of 2868 IDDM patients from 30 centres in Europe

The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to measure the prevalence of diabetic complications in stratified samples of European insulin-dependent diabetic (IDDM) patients. As diet may be related to diabetic complications, nutritional intake was analysed in the study population. The aims of this first nutritional paper are to describe the nutrient intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe, to investigate the degree of regional differences in nutrient intake and to compare current intakes with recommended levels. Nutritional intake from 1458 male and 1410 female IDDM patients was assessed by a validated 3-day record (two weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was 2390 +/- 707 kcal/day. Mean protein intake was 1.5 +/- 0.5 g/kg body weight. Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from saturated fat. The Italian centres reported lower total and saturated fat intakes compared with other centres. Recommendations from the Diabetes and Nutrition Study Group of the EASD for total fat, saturated fatty acids and carbohydrate were only achieved by 14%, 14% and 15% of patients, respectively. The data of the present study clearly indicate current problems in the nutritional intake of European IDDM patients. These findings contribute to the definition of future targets in the nutritional management of IDDM patients, to be achieved as part of the initiatives taken by the St. Vincent Declaration action programme

Protein intake and urinary albumin excretion rates in the EURODIAB IDDM complications study

For people with insulin-dependent diabetes mellitus (IDDM) renal disease represents a life-threatening and costly complication. The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to determine the prevalence of renal complications and putative risk factors in stratified samples of European individuals with IDDM. The present study examined the relationship between dietary protein intake and urinary albumin excretion rate (AER). Food intake was assessed centrally by a standardized 3-day dietary record. Urinary AER was determined in a central laboratory from a timed 24-h urine collection, Complete data were available from 2696 persons with IDDM from 30 centres in 16 European countries. In individuals who reported protein consumption less than 20 % of total food energy intake, mean AER was below 20 mu g/min. In those in whom protein intake constituted more than 20 %, mean AER increased, a trend particularly pronounced in individuals with hypertension and/or poor metabolic control. Trends reached statistical significance for intakes of total protein (% of energy, p = 0.01) and animal protein (% of energy, p = 0.02), while no association was seen for vegetable protein (p = 0.83), These findings support the current recommendation for people with diabetes not to exceed a protein intake of 20 % of total energy. Monitoring and adjustment of dietary protein appears particularly desirable for individuals with AER exceeding 20 mu g/min (approximately 30 mg/24 h), especially when arterial pressure is raised and/or diabetic control is poor