Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type two diabetes: The Veterans Affairs Diabetes Trial.

Background: Intensive glycemic control reduced the risk of coronary artery disease (CAD) events among White ACCORD study participants with the haptoglobin (Hp)2-2 phenotype, and not among participants without the Hp2-2 phenotype. It is unknown whether these results persist in a population with more severe diabetes. Methods: Haptoglobin phenotype was measured in 1746 (97 %) samples from the Veterans Affairs Diabetes Trial (VADT) randomized controlled trial. Multivariable-adjusted Cox regression models assessed the effect of intensive therapy on CAD risk among participants with and without the Hp2-2 phenotype separately and when stratified within pre-specified race/ethnicity-based subgroups. Time-varying (achieved) HbA1c data (<7.0 % or ≥8.0 % compared to 7.0-7.9, updated every 3 months) were also analyzed in relation to CAD risk within each phenotype. Results: 567 (32.5 %) participants had the Hp2-2 phenotype. Compared to standard therapy, intensive glycemic control was not associated with risk of CAD among participants with the non-Hp2-2 or the Hp2-2 phenotype or for any race/ethnicity-based group. Compared to HbA1c of 7.0-7.9 %, having HbA1c <7.0 % was not associated with CAD risk for either phenotype or among any race/ethnicity-based group. Having HbA1c ≥8.0 % was associated with an increased risk of CAD among Hispanic participants without the Hp2-2 phenotype (HR= 3.61, 95 % CI: 1.54-8.41, p-interaction=0.53). Conclusion: The effect of intensive glycemic therapy on CAD events was not dependent on Hp phenotype in the VADT study of veterans with severe diabetes who may represent a population where Hp phenotype information would not be useful for personalizing diabetes management. However, further research is needed to determine if these results are conclusive.

Co-Development of Three Dietary Indices to Facilitate Dietary Intake Assessment of Pediatric Crohn's Disease Patients.

Literature on dietary behaviours of the pediatric Crohn's Disease (CD) population and the relationship between dietary intake and CD activity is limited. Three dietary indices were developed and tested to conduct dietary pattern analysis in pediatric patients with CD consuming a free diet following remission induction via exclusive enteral nutrition (n = 11). Index scores underwent descriptive and inferential analysis. The mean adjusted scores (out of 100) for the Pediatric Western Diet Index, Pediatric Prudent Diet Index, and Pediatric-Adapted 2010 Alternate Healthy Eating Index (PA2010-AHEI) were 29.82 ± 15.22, 34.25 ± 15.18, and 51.50 ± 11.69, respectively. The mean Western-to-Prudent ratio was 0.94 ± 0.55. A significant correlation (r = -0.71) and relationship (F[1, 9] = 9.04, P < 0.05, R2 = 0.501) between the Western-to-Prudent ratio and PA2010-AHEI was found. The results suggest participants were not following a Western or Prudent diet, and were consuming foods not captured by the indices. More research is needed to describe dietary intake of individuals with CD, validate dietary indices in diverse samples, and explore the utility of these indices in CD assessment and treatment. The co-authors hope this work will stimulate/inspire subsequent interprofessional, dietitian-led research on this topic.

Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study.

OBJECTIVE: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. RESEARCH DESIGN AND METHODS: Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol. RESULTS: While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82-1.32) or with (0.84, 0.63-1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29-0.76, Pinteraction = 0.01). CONCLUSIONS: Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype.

Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study.

BACKGROUND: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes. METHODS: Haptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration. RESULTS: 1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78-1.17) or with (0.89, 0.68-1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups. CONCLUSIONS: Hp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.

National burden of rheumatoid arthritis in Canada, 1990-2019: findings from the Global Burden of Disease Study 2019 - a GBD collaborator-led study.

OBJECTIVE: The objectives of this study were: (1) to describe burden of rheumatoid arthritis (RA) and trends from 1990 to 2019 using the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) data, (2) to describe age and sex differences in RA and (3) to compare Canada's RA burden to that of other countries. METHODS: Disease burden indicators included prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life-years (DALYs). GBD estimated fatal and non-fatal outcomes using published literature, survey data and health insurance claims. Data were analysed by Bayesian meta-regression, cause of death ensemble model and other statistical methods. DALYs for Canada were compared with DALYs of countries with similarly high Socio-Demographic Index values. RESULTS: In Canada, the RA prevalence rate increased by 27% between 1990 and 2019, mortality rate decreased by 27%, YLL rate decreased by 30%, YLD increased by 27% and DALY rate increased by 13%, all age standardised. The decline in RA mortality and YLL rates was especially pronounced after 2002. The disease burden was higher in females for all indicators, and DALY rates were higher among older age groups, peaking at age 75-79 years. Prevalence and DALYs were higher in Canada compared with global rates. CONCLUSION: Trends in RA burden indicators over time and differences by age and sex have important implications for Canadian policy-makers, researchers and care providers. Early identification and management of RA in women may help reduce the overall burden of RA in Canada.

Developmental Trajectory of Body Weight in Youths at Risk for Major Mood Disorders.

Importance: Mood disorders are associated with increased body weight, especially in females, but it remains unknown when the weight increase starts. Objectives: To examine sex-specific weight trajectories associated with familial mood disorder risk and determine the age at which youth at familial risk for mood disorders begin to diverge in weight from controls. Design, Setting, and Participants: This community-based, single-center, acceleration cohort study of youth at familial risk for mood disorders and controls with yearly follow-ups (mean [SD], 5 [2.1] years) from January 1, 2014, to December 31, 2022, assessed 394 unaffected female and male offspring (aged 3 to 20 years) of parents with or without a mood disorder. Parents with mood (depressive or bipolar) disorders were recruited through adult mental health services. Parents of control participants were matched on age and socioeconomic factors and recruited through acquaintance referrals or schools. Exposures: The youth in the familial mood risk group had at least 1 parent with a major mood disorder, whereas control youth did not have a parent with a mood disorder. Main Outcomes and Measures: Body mass indexes (BMIs) were calculated as weight in kilograms divided by height in meters squared from measured weight and height at annual assessments and then converted to age- and sex-adjusted z scores (zBMIs). Repeated-measure regressions examined the association between zBMI and age in youth at familial risk of mood disorders and controls while accounting for sex. Sensitivity analyses accounted for socioeconomic status, prematurity, and birth weight. Results: Of 394 participants (mean [SD] age, 11.5 [3.6] years; 203 [51.5%] female), youths at familial risk for mood disorders showed overall no difference in body weight (ß = 0.12; 95% CI, 0.01-0.24) from controls. A sex-specific difference was detected, with females at familial risk showing a rapid peripubertal increase in body weight, leading to significantly increased zBMIs at 12 years and older compared with controls (ß = 0.57; 95% CI, 0.31-0.82) independent of socioeconomic status, prematurity, or birth weight. Males did not differ from controls at any age. Conclusions and Relevance: In this cohort study, females with a family history of mood disorders were prone to weight gain starting around puberty and predating mood disorder onset. Early interventions aiming to prevent adverse mental and physical outcomes in this vulnerable group need to start in childhood.

Dietary potassium liberalization with fruit and vegetables versus potassium restriction in people with chronic kidney disease (DK-Lib CKD): a clinical trial protocol.

BACKGROUND: Potassium regulation in the body is primarily done in the kidney. In addition to this, hyperkalemia, occurs in approximately 10% of individuals with chronic kidney disease (CKD) and is associated with elevated all-cause mortality. Individuals with CKD are often told to restrict dietary potassium (K), however, this recommendation is based on low quality evidence. Reduced quality of life, limited dietary choices and nutritional deficiencies are all potential negative outcomes that may occur when restricting dietary K in CKD patients. There is a need for randomized controlled trials investigating the impact of dietary K modification on serum K concentrations in people with CKD. METHODS: A randomized 2-period crossover design comparing a liberalized K fruit and vegetable diet where participants will be required to consume ~ 3500 mg of dietary K daily, to a standard K restricted diet where participants will be required to consume < 2000 mg of dietary K daily. All participants will begin on a liberalized K run-in period for 2 weeks where they will receive fruit and vegetables home deliveries and for safety will have clinical chemistry, including serum potassium measurements taken after 1 week. Participants will then be randomized into either liberalized K or standard K diet for six weeks and then crossover to the other intervention for another 6 weeks after a 2-week washout period. DISCUSSION: 30 male and female CKD outpatients, ≥ 18 years of age, who have an estimated glomerular filtration rate (eGFR) between 15 and 45 ml/min/1.73m2 and serum K between 4.5 and 5.5 mEq/L. This design would have greater than 80% power to detect a difference of 0.35 mEq/L serum K between groups. Anthropometric measurements, clinical chemistry, dietary recalls, physical function assessments, as well as a quality of life assessments will also be measured in this trial. These findings will provide high quality evidence for, or against, recommendations for dietary K restriction in individuals living with CKD. The removal of K restriction could provide individuals living with CKD more dietary choice leading to improved dietary status and quality of life. TRIAL REGISTRATION: This trial has received approval from the University of Manitoba Research Ethics board (HS25191 (B2021:104)).

Relationship Between Time-Varying Achieved High-Density Lipoprotein Cholesterol and Risk of Coronary Events Depends on Haptoglobin Phenotype Within the ACCORD Lipid Study.

Background The Hp (haptoglobin)2-2 phenotype (~40% of people) is associated with dysfunctional high-density lipoprotein (HDL) that is heavily oxidized in hyperglycemia, which may explain why raising HDL-cholesterol (HDL-C) does not reliably prevent coronary artery disease (CAD) in diabetes. Methods and Results In this observational study using longitudinal data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, time-varying (achieved) HDL-C updated at 4, 8, and 12 months, and annually thereafter over a mean of 4.7 years, was analyzed in relation to risk of CAD and secondary outcomes using Cox proportional hazards regression with time-varying covariables among participants with (n=1781) and without (n=3191) the Hp2-2 phenotype. HDL-C did not differ between the phenotypes throughout the study. Having low HDL-C (<40 mg/dL for male participants and <50 mg/dL for female participants) was associated with a greater risk of CAD compared with non-low HDL-C among participants with the non-Hp2-2 phenotype (hazard ratio [HR], 1.48 [95% CI, 1.18-1.87]) but not among the Hp2-2 phenotype (HR, 0.97 [95% CI, 0.70-1.35]; P interaction=0.03). Similarly, an inverse relationship was observed between HDL-C quintiles and CAD risk among participants without the Hp2-2 phenotype, whereas no significant inverse relationship was observed among participants with the Hp2-2 phenotype (P interaction=0.38). Among the Hp2-2 phenotype group, having low HDL-C was associated with higher risk of CVD mortality (HR, 2.09 [95% CI, 1.05-4.13]), and compared with the lowest HDL-C quintile, higher quintiles were associated with lower risk of CVD mortality and congestive heart failure. Conclusions Hp phenotype modified the association between HDL-C and risk of CAD in the ACCORD lipid study, suggesting that HDL dysfunction in the Hp2-2 phenotype may hinder CAD-protective properties of HDL-C.

The Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Events Depends on Haptoglobin Phenotype Among White and Black ACCORD Participants.

OBJECTIVE: Intensive glycemic therapy reduced coronary artery disease (CAD) events among White participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with the haptoglobin (Hp)2-2 phenotype, while participants without the Hp2-2 phenotype had no CAD benefit. The association between achieved glycated hemoglobin (HbA1c) and CAD for each Hp phenotype remains unknown. RESEARCH DESIGN AND METHODS: Achieved HbA1c was similar in each phenotype throughout the study. Prospectively collected HbA1c data (categorized as <6.0%, 6.0-6.5%, 6.6-6.9%, or ≥8.0% compared with 7.0-7.9%) from the ACCORD study, updated every 4 months over a median of 4.7 years, were analyzed in relation to CAD in the Hp2-2 (n = 3,322) and non-Hp2-2 (n = 5,949) phenotypes separately overall, and within White (63%, 37% Hp2-2) and Black (19%, 26% Hp2-2) participants using Cox proportional hazards regression with time-varying covariables. RESULTS: Compared with HbA1c of 7.0-7.9%, having HbA1c ≥8.0% was associated with CAD risk among White (adjusted HR [aHR] 1.43, 95% CI 1.03-1.98) and Black (2.86, 1.09-7.51) participants with the Hp2-2 phenotype, but not when all Hp2-2 participants were combined overall (1.30, 0.99-1.70), and not among participants without the Hp2-2 phenotype. HbA1c <7.0% was not associated with a lower risk of CAD for any Hp phenotype. CONCLUSIONS: Achieving HbA1c >8.0% compared with 7.0-7.9% was consistently associated with incident CAD risk among White and Black ACCORD participants with the Hp2-2 phenotype, while no association was observed among participants without the Hp2-2 phenotype. We found no evidence that HbA1c concentration <7.0% prevents CAD in either Hp phenotype group.

Reducing Dietary Acid With Fruit and Vegetables Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD): A Clinical Research Protocol.

Background: Individuals with chronic kidney disease (CKD) can develop metabolic acidosis which, in turn, is associated with faster progression of CKD and an increased need for dialysis. Oral sodium bicarbonate (the current standard of care therapy for metabolic acidosis) is poorly tolerated leading to low adherence. Base-producing or alkalizing Fruit and vegetables have potential as an alternative treatment for metabolic acidosis as they have been shown to reduce acid load arising from the diet. Objective: This trial will evaluate the feasibility of providing base-producing fruit and vegetables as a dietary treatment for metabolic acidosis, compared with oral sodium bicarbonate. Design: A 2-arm, open-label, dual-center, randomized controlled feasibility trial. Setting: Two Canadian sites: a nephrology clinic in Winnipeg, Manitoba, and a nephrology clinic in Halifax, Nova Scotia. Participants: Adult participants with G3-G5 CKD and metabolic acidosis. Measurements: Participants will undergo baseline measurements and attend 5 study visits over 12 months at which they will have a measurement of feasibility criteria as well as blood pressure, blood and urine biochemistry, 5-repetition chair stand test (STS5), and questionnaires to assess quality of life and symptoms. Furthermore, participants fill out Automated Self-Administered 24-hour recalls (ASA-24) in the beginning, middle, and end of trial. Methods: A total of 40 eligible participants will be randomized 1:1 to either base-producing fruit and vegetables (experimental) group or sodium bicarbonate (control) group, beginning from a daily dose of 1500 mg. Limitations: Using self-administered dietary assessments, lack of supervision over the consumption of study treatments and the possible disappointment of the control group for not receiving fruit and vegetables would be considered as limitations for this study. However, we are planning to undertake proper practices to overcome the possible limitations. These practices are discussed throughout the article in detail. Conclusions: This study will generate data on base-producing fruit and vegetables consumption as a dietary treatment for metabolic acidosis in CKD. The data will be used to design a future multi-center trial looking at slowing CKD progression in people with metabolic acidosis. Trial Registration: This study is registered on clinicaltrials.gov with the identifier NCT05113641.

Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) courent le risque de développer une acidose métabolique, laquelle est associée à une progression plus rapide de l'IRC et à un besoin accru de dialyse. La prise de bicarbonate de sodium par voie orale (la norme actuelle de traitement de l'acidose métabolique) est mal tolérée, ce qui se traduit par une faible adhérence. Les fruit et légumes basiques ou alcalifiants ont un potentiel de traitement alternatif pour l'acidose métabolique, car il a été démontré qu'ils peuvent réduire la charge acide provenant de l'alimentation. Objectif: cet essai permettra d'évaluer la faisabilité d'un traitement alimentaire de l'acidose métabolique, en misant sur la consommation de fruit et légumes basiques ou alcalifiants, par rapport à la prise de bicarbonate de sodium par voie orale. Type d'étude: essai de faisabilité contrôlé, randomisé, ouvert, à deux bras, mené dans deux centres. Cadre: deux sites canadiens, soit une clinique de néphrologie à Winnipeg (Manitoba) et une autre à Halifax (Nouvelle-Écosse). Sujets: des patients adultes atteints d'IRC de stade G3-G5 et d'acidose métabolique. Mesures: les participants seront soumis à des mesures initiales et devront se présenter à cinq visites d'étude réparties sur 12 mois. Au cours de chacune, les patients subiront une mesure des critères de faisabilité, une mesure de la pression artérielle, un bilan sanguin et urinaire, un test de lever de chaise à cinq répétitions (STS5 ­ Five Times Sit to Stand Test) et devront répondre à des questionnaires évaluant la qualité de vie et les symptômes. Les participants devront également utiliser un outil en ligne de rappels alimentaires de 24 heures autoadministrés et automatisés (ASA24 ­ Automated Self-Administered 24-hours) au début, à mi-parcours et à la fin de l'essai. Méthodologie: 40 patients admissibles seront randomisés (1:1) dans le groupe expérimental (fruit et légumes basiques ou alcalifiants) ou dans le groupe témoin (bicarbonate de sodium) avec une dose quotidienne initiale de 1 500 mg. Limites: l'utilisation d'outils d'évaluation alimentaire autoadministrés, le manque de supervision de la consommation des traitements à l'étude et la possible déception du groupe témoin de ne pas recevoir de fruit et légumes constituent des limites pour cette étude. Nous prévoyons cependant adopter des pratiques appropriées pour surmonter ces possibles limites. Ces pratiques sont discutées plus en détail dans le manuscrit. Conclusion: cette étude produira des données sur la consommation de fruit et légumes basiques ou alcalifiants comme traitement alimentaire pour l'acidose métabolique en contexte d'IRC. Ces données seront utilisées pour concevoir un futur essai multicentrique visant à ralentir la progression de l'IRC chez les personnes atteintes d'acidose métabolique. Enregistrement de l'essai: Cette étude a reçu l'approbation du Conseil d'éthique de la recherche en santé de l'Université du Manitoba (HS24768 [B2021:025]) et est enregistrée sur ClinicalTrials.gov avec l'identifiant NCT05113641.

Interrupting bedtime to reverse frailty levels in acute care: a study protocol for the Breaking Bad Rest randomized controlled trial.

BACKGROUND: Hospitalized older patients spend most of the waking hours in bed, even if they can walk independently. Excessive bedrest contributes to the development of frailty and worse hospital outcomes. We describe the study protocol for the Breaking Bad Rest Study, a randomized clinical trial aimed to promoting more movement in acute care using a novel device-based approach that could mitigate the impact of too much bedrest on frailty. METHODS: Fifty patients in a geriatric unit will be randomized into an intervention or usual care control group. Both groups will be equipped with an activPAL (a measure of posture) and StepWatch (a measure of step counts) to wear throughout their entire hospital stay to capture their physical activity levels and posture. Frailty will be assessed via a multi-item questionnaire assessing health deficits at admission, weekly for the first month, then monthly thereafter, and at 1-month post-discharge. Secondary measures including geriatric assessments, cognitive function, falls, and hospital re-admissions will be assessed. Mixed models for repeated measures will determine whether daily activity differed between groups, changed over the course of their hospital stay, and impacted frailty levels. DISCUSSION: This randomized clinical trial will add to the evidence base on addressing frailty in older adults in acute care settings through a devices-based movement intervention. The findings of this trial may inform guidelines for limiting time spent sedentary or in bed during a patient's stay in geriatric units, with the intention of scaling up this study model to other acute care sites if successful. TRIAL REGISTRATION: The protocol has been registered at clinicaltrials.gov (identifier: NCT03682523).

Relationship of body mass index with frailty and all-cause mortality among middle-aged and older adults.

BACKGROUND: Parallel to growth of aging and obese populations, the prevalence of metabolic diseases is rising. How body mass index (BMI) relates to frailty and mortality across frailty levels is controversial. We examined the associations of high BMI with frailty and mortality and explored the effects of percent body fat on these associations. METHODS: We included 29,937 participants aged ≥50 years from the 2001-2006 National Health and Nutrition Examination Survey (NHANES) cohorts (N=6062; 53.7% females) and from wave 1 (2004) of Survey of Health, Ageing and Retirement in Europe (SHARE) (N=23,875; 54% females). BMI levels were categorized as: normal: 18.5-24.9 kg/m2, overweight: 25.0-29.9, obese grade 1: 30.0-34.9, and obese grade 2 or 3: >35.0. A frailty index (FI) was constructed excluding nutrition-related items: 36 items for NHANES and 57 items for SHARE. We categorized the FI using 0.1-point increments: FI ≤ 0.1 (non-frail), 0.1 < FI ≤ 0.2 (very mildly frail), 0.2 < FI ≤ 0.3 (mildly frail), and FI > 0.3 (moderately/severely frail). Percent body fat was measured using DXA for NHANES participants. All-cause mortality data were obtained until 2015 for NHANES and 2017 for SHARE to estimate 10-year mortality risk. All analyses were adjusted for age, sex, educational, marital, employment, and smoking statuses. RESULTS: Mean age of participants was 63.3±10.2 years for NHANES and 65.0±10.0 years for SHARE. In both cohorts, BMI levels ≥25 kg/m2 were associated with higher frailty, compared to normal BMI. In SHARE, having a BMI level greater than 35 kg/m2 increased mortality risk in participants with FI≤0.1 (HR 1.31, 95%CI 1.02-1.69). Overweight participants with FI scores >0.3 were at lower risk for mortality compared to normal BMI [NHANES (0.79, 0.64-0.96); SHARE (0.71, 0.63-0.80)]. Higher percent body fat was associated with higher frailty. Percent body fat significantly mediated the relationship between BMI levels and frailty but did not mediate the relationship between BMI levels and mortality risk. CONCLUSIONS: Being overweight or obese is associated with higher frailty levels. In this study, we found that being overweight is a protective factor of mortality in moderately/severely frail people and obesity grade 1 may be protective for mortality for people with at least a mild level of frailty. In contrast, obesity grades 2 and 3 may be associated with higher mortality risk in non-frail people. The relationship between BMI and frailty is partially explained by body fat.

Many authors of publicly available top-selling nutrition books in Canada are without clinical nutrition credentials, do not cite evidence, and promote their own services or products.

The accuracy of books as public nutrition resources varies substantially; whether authors of publicly available nutrition books possess related experience, cite scientific evidence, or have other financial incentives has not been assessed thoroughly. This study aimed to determine if publicly available top-selling nutrition books are written by authors who (1) have relevant expertise, (2) cite scientific evidence, and (3) benefit financially in other ways. Best-selling nutrition books were gathered from Amazon Canada. Differences in scientific citations and financial incentives were compared between authors with and without credentials. Authors who were Doctor of Medicine (MD), registered dietitians (RD), chiropractors, or naturopathic doctors had more in-text citations (56% versus 25%; p = 0.014) and cited more scientific articles (83% versus 50%; p = 0.0045) compared to all other authors. The majority of authors of publicly available top-selling nutrition books in Canada did not have MD/RD credentials. Many of the authors promoted their own services or products, regardless of credentials.

Eating Timing and Frequency as a Predictor of Hospitalization and/or Mortality From Coronary Artery Disease: The Linked CCHS-DAD-CMDB 2004-2013 Study.

Background: Coronary artery disease (CAD) is a major overlapping challenge in both clinical and public health realms due to high rates of hospitalization and mortality. Despite nutrition being a key risk factor for CAD, little is known about eating timing and frequency in Canadians or their relation to risk of hospitalization and/or mortality from CAD. Methods: Breakfast consumption, between-meal consumption, eating frequency, and established CAD risk factors were assessed at baseline in 13,328 adults free of cancer and CAD from the 2004 Canadian Community Health Survey, Cycle 2.2, Nutrition Focus and were linked to administrative health databases to determine incidence of hospitalization and/or mortality from CAD in the following 9 years. Multivariable-adjusted hazard ratios with 95% confidence intervals estimated from Cox proportional hazards models were computed to test for associations between eating timing/frequency and hospitalization and/or mortality from CAD (n = 746 cases). Results: Skipping breakfast (12.0% of participants) and engaging in between-meal consumption (90.2%) were common practices, as was eating 4-5 times per day (55.2%). Skipping breakfast, between-meal consumption, and eating more or less than 4-5 times/day were strongly and bi-directionally associated with many sociodemographic, lifestyle, and metabolic risk factors at baseline. No associations were observed between skipping breakfast, between-meal consumption, or eating frequency and risk of hospitalization and/or mortality from CAD. Conclusions: Skipping breakfast, between-meal consumption, and eating frequency were associated with numerous established risk and preventative factors for CAD at baseline but were not directly associated with the risk of hospitalization and/or mortality from CAD in this cohort of Canadian adults.

Introduction: La maladie coronarienne (MC) est un enjeu majeur chevauchant les domaines clinique et de santé publique en raison des taux élevés d'hospitalisation et de mortalité. Bien que la nutrition soit un facteur de risque fondamental de la MC, on en connaît peu sur le moment et la fréquence de la consommation d'aliments chez les Canadiens ou sur leur relation au risque d'hospitalisation et/ou de mortalité en raison de la MC. Méthodes: Nous avons initialement évalué la prise du déjeuner, la consommation entre les repas, la fréquence de la consommation d'aliments et les facteurs de risque établis de MC de 13 328 adultes indemnes de cancer et de MC de l'Enquête sur la santé dans les collectivités canadiennes de 2004, cycle 2.2, volet nutrition, et avons lié les bases de données administratives en santé pour déterminer la fréquence d'hospitalisation et/ou de mortalité en raison de la MC dans les neuf années subséquentes. Nous avons calculé les rapports de risque ajustés à plusieurs variables à intervalles de confiance à 95 % estimés à partir des modèles à risques proportionnels de Cox pour vérifier les associations entre le moment et la fréquence de la consommation d'aliments et l'hospitalisation et/ou la mortalité en raison de la MC (n = 746 cas). Résultats: L'absence du déjeuner (12,0 % des participants), la consommation d'aliments entre les repas (90,2 %) et la consommation d'aliments de 4 à 5 fois par jour (55,2 %) étaient des pratiques courantes. L'absence du déjeuner, la consommation d'aliments entre les repas et la consommation d'aliments plus ou moins 4-5 fois/jour étaient fortement et bidirectionnellement associées aux facteurs de risque sociodémographiques, liés au mode de vie et métaboliques initiaux. Nous n'avons observé aucune association entre l'absence du déjeuner, la consommation d'aliments entre les repas ou la fréquence de la consommation d'aliments, et le risque d'hospitalisation et/ou de mortalité en raison de la MC. Conclusions: L'absence du déjeuner, la consommation d'aliments entre les repas et la fréquence de la consommation d'aliments étaient associées à de nombreux risques établis et de facteurs préventifs initiaux de la MC, mais n'étaient pas directement associées au risque d'hospitalisation et/ou de mortalité en raison de la MC dans cette cohorte d'adultes canadiens.

Prospective study of breakfast frequency and timing and the risk of incident type 2 diabetes in community-dwelling older adults: the Cardiovascular Health Study.

BACKGROUND: No evidence-based recommendations regarding optimal breakfast frequency and timing and type 2 diabetes mellitus (T2DM) exist for older adults because of limited studies. OBJECTIVES: We sought to prospectively assess relations between breakfast frequency and timing and T2DM risk among older adults and determine whether these depended on sex or cardiometabolic risk factors. METHODS: Weekly breakfast frequency and usual daily breakfast time were assessed by questionnaire at baseline in 3747 older adults (aged ≥ 65 y) from the Cardiovascular Health Study (CHS) who were free of cancer and T2DM and followed for 17.6 y. Multivariable-adjusted hazard ratios (aHRs) with 95% CIs estimated from Cox proportional hazards models were used to quantify associations with T2DM. RESULTS: Most CHS participants (median age: 74 y; IQR: 71-78 y) consumed breakfast daily (85.5%), and 73% had their first daily eating occasion between 07:00 and 09:00, both of which were associated with higher socioeconomic status, factors that are indicative of a healthier lifestyle, and lower levels of cardiometabolic risk indicators at baseline. During follow-up, 547 T2DM cases were documented. No strong evidence was observed linking breakfast frequency and risk of T2DM. Compared with participants whose breakfast timing (first eating occasion of the day) was 07:00-09:00, those who broke fast after 09:00 had an aHR for T2DM of 0.71 (95% CI: 0.51, 0.99). This association was present in participants with impaired fasting glucose at baseline (aHR: 0.61; 95% CI: 0.39, 0.95) but not in those without (aHR: 0.83; 95% CI: 0.50, 1.38). No associations between eating frequency or timing and T2DM were observed within other prespecified subgroups. CONCLUSIONS: Eating breakfast daily was not associated with either higher or lower risk of T2DM in this cohort of older adults, whereas a later (after 09:00) daily first eating occasion time was associated with lower T2DM risk in participants with impaired fasting glucose at baseline.This trial was registered at clinicaltrials.gov as NCT00005133.

Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial.

OBJECTIVE: The haptoglobin (Hp)2-2 phenotype (∼35-40% of people) is associated with increased oxidation and dysfunctional HDL in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL cholesterol and lower triglycerides have not reliably prevented cardiovascular disease in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. RESEARCH DESIGN AND METHODS: Cox proportional hazards regression models quantified the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n = 1,795) separately from those without (n = 3,201). RESULTS: Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable adjusted hazard ratio 0.74 [95% CI 0.60-0.90] compared with no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16 [0.87-1.56]; P interaction = 0.009). Subgroup analyses revealed that this protective effect of fenofibrate against CAD events among the non-Hp2-2 phenotype group was pronounced in participants with severe dyslipidemia (P interaction = 0.01) and in males (P interaction = 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (P interaction = 0.002). CONCLUSIONS: The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial.

Relationship between diet quality scores and the risk of frailty and mortality in adults across a wide age spectrum.

BACKGROUND: Beyond intakes of total energy and individual nutrient, eating patterns may influence health, and thereby the risk of adverse outcomes. How different diet measures relate to frailty-a general measure of increased vulnerability to unfavorable health outcomes-and mortality risk, and how this might vary across the life course, is not known. We investigated the associations of five dietary indices (Nutrition Index (NI), the energy-density Dietary Inflammatory Index (E-DII™), Healthy Eating Index-2015 (HEI-2015), Mediterranean Diet Score (MDS), and Dietary Approaches to Stop Hypertension (DASH)) with frailty and mortality. METHODS: We included 15,249 participants aged ≥ 20 years from the 2007-2012 cohorts of the National Health and Nutrition Examination Survey (NHANES). The NI combined 31 nutrition-related deficits. The E-DII is a literature-derived dietary index associated with inflammation. The HEI-2015 assesses adherence to the Dietary Guidelines of Americans. The MDS represents adherence to the traditional Mediterranean diet. DASH combines macronutrients and micronutrients to prevent hypertension. Frailty was evaluated using a 36-item frailty index. Mortality status was ascertained up to December 31, 2015. RESULTS: Participants' mean age was 47.2 ± 16.7 years and 51.7% were women. After adjusting for age, sex, race, educational level, marital and employment status, smoking, BMI, and study cohort, higher NI and E-DII scores and lower HEI-2015, MDS, and DASH scores were individually significantly associated with frailty. All dietary scores were significantly associated with 8-year mortality risk after adjusting for basic covariates and frailty: NI (hazard ratio per 0.1 point, 1.15, 95%CI 1.10-1.21), E-DII (per 1 point, 1.05, 1.01-1.08), HEI-2015 (per 10 points, 0.93, 0.89-0.97), MDS (per 1 point, 0.94, 0.90-0.97), and DASH (per 1 point, 0.96, 0.93-0.99). The associations of E-DII, HEI-2015, and MDS scores with 8-year mortality risk persisted after additionally adjusting for NI. CONCLUSIONS: NI, E-DII, HEI-2015, MDS, and DASH scores are associated with frailty and 8-year mortality risk in adults across all ages. Nevertheless, their mechanisms and sensitivity to predict health outcomes may differ. Nutrition scores have the potential to include measures of both consumption and laboratory and physical measures of exposure.

Prospective Study of Skipping Meals to Lose Weight as a Predictor of Incident Type 2 Diabetes With Potential Modification by Cardiometabolic Risk Factors: The Canadian 1995 Nova Scotia Health Survey.

BACKGROUND: Skipping meals is an increasingly common practice to lose weight among North American adults. However, the long-term effect of this practice on incident type 2 diabetes mellitus (T2DM) remains unknown. We assessed whether skipping meals to lose weight is associated with T2DM risk and whether this association is modified by cardiometabolic risk factors. METHODS: Skipping meals to lose weight was assessed by questionnaire in 2,288 adults from the 1995 Nova Scotia Health Survey and was linked to administrative health databases to determine T2DM incidence in the following 23 years. Multivariable-adjusted Cox proportional hazards models estimated hazard ratios (aHRs) and 95% confidence intervals (CIs) for T2DM. RESULTS: During follow up, 378 T2DM cases were diagnosed. Compared with participants who did not skip meals to lose weight, those who did (2.2%) had a 125% higher risk of T2DM (aHR, 2.25; 95% CI, 1.31 to 3.86). This association was no longer present after further adjustment for baseline body mass index (BMI) (aHR, 1.66; 95% CI, 0.96 to 2.85). Skipping meals to lose weight was associated with T2DM among participants who were men (n=1,135; aHR, 2.09; 95% CI, 1.09 to 4.02) or had a BMI <30 kg/m2 (n=1,676; aHR, 2.64, 95% CI, 1.15 to 6.06), elevated cholesterol (n=1,146; aHR, 2.11; 95% CI, 1.06 to 4.22), high blood pressure (n=1,133; aHR, 2.10; 95% CI, 1.10 to 4.01) and restless sleep (n=1,186; aHR, 2.19; 95% CI, 1.13 to 4.25), but not among women, those with a BMI of ≥30 kg/m2 and those without elevated cholesterol, high blood pressure or restless sleep. CONCLUSIONS: Skipping meals to lose weight may be a predictive modifiable risk factor for developing T2DM over time, potentially working in connection with other T2DM risk factors.