Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and progresses faster in males than in females. We identify sex-based differences in kidney metabolism and in the blood ...metabolome of male and female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy males displayed increased mitochondrial respiration, oxidative stress, apoptosis, and greater injury when exposed to high glucose compared with PTECs from healthy females. Male human PTECs showed increased glucose and glutamine fluxes to the TCA cycle, whereas female human PTECs showed increased pyruvate content. The male human PTEC phenotype was enhanced by dihydrotestosterone and mediated by the transcription factor HNF4A and histone demethylase KDM6A. In mice where sex chromosomes either matched or did not match gonadal sex, male gonadal sex contributed to the kidney metabolism differences between males and females. A blood metabolomics analysis in a cohort of adolescents with or without diabetes showed increased TCA cycle metabolites in males. In a second cohort of adults with diabetes, females without DKD had higher serum pyruvate concentrations than did males with or without DKD. Serum pyruvate concentrations positively correlated with the estimated glomerular filtration rate, a measure of kidney function, and negatively correlated with all-cause mortality in this cohort. In a third cohort of adults with CKD, male sex and diabetes were associated with increased plasma TCA cycle metabolites, which correlated with all-cause mortality. These findings suggest that differences in male and female kidney metabolism may contribute to sex-dependent outcomes in DKD.
Aim
To examine the effect of walking before dinner on 24-h glycemic control in individuals with type 2 diabetes using the standardized multi-site
E
xercise-
P
hysical
A
ctivity and
D
iabetes
G
lucose
...M
onitoring (E-PAraDiGM) Protocol.
Methods
Eighty participants were studied under two conditions (exercise vs. non-exercise control) separated by 72 h in a randomized crossover design. Each condition lasted 2 days during which standardized meals were provided. Exercise consisted of 50 min of treadmill walking at 5.0 km/h before the evening meal, while control involved 50 min of sitting. The primary outcome measure was mean glucose during the 24-h period following exercise (or sitting) measured by continuous glucose monitoring.
Results
Of the 80 participants who were initially randomized, 73 completed both exercise and control. Sixty-three participants 29 males, 34 females; age = 64 ± 8 years, body mass index = 30.5 ± 6.5 kg/m
2
and HbA1c = 51 ± 8 mmol/mol (6.8 ± 0.7%), mean ± SD complied with the standardized diets and had complete continuous glucose monitoring data. Exercise did not affect mean 24-h glucose compared to control (0.03 mmol/L; 95% CI − 0.17, 0.22,
P
= 0.778) but individual differences between conditions ranged from − 2.8 to +1.8 mmol/L. Exercise did not affect fasting glucose, postprandial glucose or glucose variability. Glucose concentrations measured by continuous glucose monitoring were reduced during the 50 min of walking in exercise compared to sitting in control (− 1.56 mmol/L; 95% CI − 2.18, − 0.95,
p
< 0.001).
Conclusion
Contrary to previous acute exercise studies, 50 min of walking before dinner in the E-PAraDiGM protocol did not affect 24-h glucose profiles. However, highly heterogeneous responses to exercise were observed.
Trial registration
: NCT02834689.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
School‐based healthy living interventions are widely promoted as strategies for preventing obesity. The peer‐led Healthy Buddies™ curriculum has been shown to improve obesity‐related outcomes in ...school‐aged children. We examined whether these improvements existed among subgroups of children stratified by sex, income level and urban/rural geography. In a cluster‐randomized controlled trial, elementary schools in Manitoba, Canada, were randomly allocated to Healthy Buddies™ (10 schools, 340 students) or standard curriculum (10 schools, 347 students). Healthy Buddies™ participants had 21weekly lessons on healthy eating, physical activity and self‐efficacy, delivered by children age 9–12 to children age 6–8. We assessed pre‐ and post‐intervention body mass index (BMI) z‐scores, waist circumference, healthy living knowledge, dietary intake and self‐efficacy among the younger children. Compared to standard curriculum (n = 154), Healthy Buddies™ participants (n = 157) experienced a greater reduction in waist circumference (−1.7 cm; 95% confidence interval CI−2.8, −0.5 cm) and improved dietary intake (4.6; 95% CI 0.9, 8.3), healthy living knowledge (5.9; 95% CI 2.3, 9.5) and self‐efficacy (5.3; 95% CI 1.0, 9.5) scores. In subgroup analyses, effects for waist circumference (−2.0 cm; 95% CI −3.6, −0.5), healthy living knowledge (9.1; 95% CI 4.4, 13.8) and self‐efficacy (8.3; 95% CI 3.3, 13.3) were significant among boys. Dietary intake (10.5; 95% CI 5.5, 15.4), healthy living knowledge (9.8; 95% CI 4.5, 15.0) and self‐efficacy (6.7; 95% CI 0.7, 12.7) improved among urban‐dwelling but not rural‐dwelling children. Healthy Buddies™ was effective for boys and children living in urban settings. Enhanced curricula may be needed to improve program effectiveness for select subgroups of school‐aged children.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplant recipients (KTR). Two risk factors for cardiovascular disease that have not been examined in this ...population are arterial compliance and aerobic capacity. The primary objective was to determine small and large artery compliance and aerobic endurance in KTR. A secondary objective was to explore the relationship between aging and arterial compliance and aerobic endurance in KTR.
Sixty-two clinically stable KTR were recruited from the University of Alberta Renal Transplant Clinic. Small and large artery compliance was assessed using computerized arterial pulse waveform analysis. Aerobic endurance was determined using the six-minute walk test. Age-matched normative data from healthy individuals was used for comparison.
Small arterial compliance was lower in KTR (5.5+/-3 ml/mm Hg x 100) compared to age-matched healthy individuals' predicted values (7.9+/-0.9 ml/mm Hg x 100, P<0.0001). No difference was found for large artery compliance between KTR (16.0+/-6.6 ml/mm Hg x 10) and age-matched healthy predicted values (15.2+/-1.3 ml/mm Hg x 10, P=0.5). Small and large artery compliance were 35% (P=0.026) and 36% (P=0.005) higher in younger (<51 years) versus older (>51 years) KTR, respectively. The six-minute walk distance was 28% lower in KTR (495+/-92 m) compared to healthy age-predicted values (692+/-56 m P<0.0001).
Compromised arterial compliance and poor aerobic endurance may partially explain the high incidence of cardiovascular disease in KTR. Interventions demonstrated to improve these parameters may afford substantial clinical benefit in this population.
Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to ...determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects.
We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points.
From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m
; 95% confidence interval CI -1.10 to 0.36;
9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06;
0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome.
Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners.
PROSPERO-CRD42015019749.
Our aim in this study was to describe the clinical and social characteristics of 2 Canadian cohorts of adolescents with diabetes.
Participants from the Improving renal Complications in Adolescents ...with type 2 diabetes through REsearch (iCARE) study (n=322) and the Early Determinants of Cardio-Renal Disease in Youth With Type 1 Diabetes (n=199) study were compared.
Adolescents were 10 to 18 years of age (mean ± standard deviation: 14.8±2.4 years). The T2DM cohort had a shorter duration of diabetes. Both groups had glycated hemoglobin levels above target. The type 2 diabetes (T2D) cohort was comprised of predominantly Indigenous youth. The type 1 diabetes (T1D) cohort was 58.3% European/Caucasian, with a high proportion (41.7%) of visible minority groups (Afro-Caribbean, Asian/Pacific Islander, Hispanic). The prevalence of obesity, hypertension, left ventricular hypertrophy, albuminuria and hyperfiltration was higher in the T2D cohort. The T1D cohort was more socially and economically advantaged in all 4 dimensions of health inequality.
There are significant differences in clinical and social characteristics of adolescents with T2D and T1D in Canada. Both have inadequate glycemic control with evidence of onset and progression of diabetes-related complications.
L’objectif de notre étude était de décrire les caractéristiques cliniques et sociales de 2 cohortes canadiennes d’adolescents diabétiques.
Nous avons comparé les participants à l’étude Improving renal Complications in Adolescents with type 2 diabetes through REsearch (iCARE) (n = 322) et les participants à l’étude Early Determinants of Cardio-Renal Disease in Youth With Type 1 Diabetes (n = 199).
Les adolescents avaient de 10 à 18 ans (moyenne ± écart type : 14,8 ± 2,4 ans). La cohorte atteinte du diabète de type 2 (DT2) souffrait du diabète depuis moins longtemps. Les 2 groupes avaient des concentrations d’hémoglobine glyquée au-dessus des valeurs visées. La cohorte atteinte du DST2 était majoritairement composée de personnes autochtones. La cohorte atteinte du diabète de type 1 (DT1) était composée de 58,3 % d’Européens blancs, dont une forte proportion (41,7 %) de groupes des minorités visibles (Afro-Antillais, Asiatiques/insulaires du Pacifique, Hispaniques). La prévalence de l’obésité, de l’hypertension, de l’hypertrophie ventriculaire gauche, de l’albuminurie et de l’hyperfiltration était plus élevée dans la cohorte atteinte du DT2. La cohorte atteinte du DT1 était plus socialement et économiquement favorisée dans les 4 dimensions des inégalités en santé.
Il existe des différences significatives entre les caractéristiques cliniques et sociales des adolescents atteints du DT2 et celles des adolescents atteints du DT1 au Canada. Les 2 cohortes ont une mauvaise régulation de la glycémie qui se manifeste par l’apparition et la progression des complications liées au diabète.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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