Portfolio Diet Score and Risk of Cardiovascular Disease: Findings From 3 Prospective Cohort Studies.

BACKGROUND: The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term adherence to the diet and CVD risk. The primary objective was to examine the relationship between the Portfolio Diet Score (PDS) and the risk of total CVD, coronary heart disease (CHD), and stroke. METHODS: We prospectively followed 73 924 women in the Nurses' Health Study (1984-2016), 92 346 women in the Nurses' Health Study II (1991-2017), and 43 970 men in the Health Professionals Follow-up Study (1986-2016) without CVD or cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every 4 years using a PDS that positively ranks plant protein (legumes), nuts and seeds, viscous fiber sources, phytosterols (mg/day), and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and cholesterol. RESULTS: During up to 30 years of follow-up, 16 917 incident CVD cases, including 10 666 CHD cases and 6473 strokes, were documented. After multivariable adjustment for lifestyle factors and a modified Alternate Healthy Eating Index (excluding overlapping components), comparing the highest with the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled hazard ratio [HR], 0.86 [95% CI, 0.81-0.92]; Ptrend<0.001), CHD (pooled HR, 0.86 [95% CI, 0.80-0.93]; Ptrend=0.0001), and stroke (pooled HR, 0.86 [95% CI, 0.78-0.95]; Ptrend=0.0003). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR, 0.92 [95% CI, 0.89-0.95]), CHD (pooled HR, 0.92 [95% CI, 0.88-0.95]), and stroke (pooled HR, 0.92 [95% CI, 0.87-0.96]). Results remained consistent across sensitivity and most subgroup analyses, and there was no evidence of departure from linearity for CVD, CHD, or stroke. In a subset of participants, a higher PDS was associated with a more favorable blood lipid and inflammatory profile. CONCLUSIONS: The PDS was associated with a lower risk of CVD, including CHD and stroke, and a more favorable blood lipid and inflammatory profile, in 3 large prospective cohorts.

Effects of psychopathic traits on preferential recall and recognition of emotionally evocative photos.

Psychopathic traits are associated with impaired emotional processing. The present study examines the potential association between psychopathic traits and memory for emotional stimuli. Although a significant body of research suggests that memory is heightened for emotional stimuli, it is unclear how psychopathic traits may disrupt this process. Eighty-two male jail inmates completed an emotional memory task as well as portions of a standardised memory assessment. Psychopathic traits were not associated with the ability to freely recall images of positive, negative or neutral valence that participants had seen more than 15 min prior; psychopathic traits were also not associated with the ability to recognise these previously viewed images when shown them again. Exploratory analyses indicated trends toward reduced accuracy in recognising both positive and negative, but not neutral, emotional stimuli in individuals with higher levels of interpersonal and affective traits of psychopathy. As expected, psychopathy was unrelated to non-emotion-related memory functioning in auditory and visual domains as measured by the Wechsler Memory Scales 4th Edition. Overall, these results do not support the hypothesis that psychopathic traits significantly interfere with memory for emotional stimuli.

Nordic dietary patterns and cardiometabolic outcomes: a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials.

AIMS/HYPOTHESIS: Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I2=88%, pQ<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], pMD=0.05; substantial heterogeneity: I2=89%, pQ<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p<0.05). For the other outcomes there were 'trivial' reductions or no effect. The certainty of the evidence was low for total CVD incidence and LDL-cholesterol; moderate to high for CVD mortality, established lipid targets, adiposity markers, glycaemic control, blood pressure and inflammation; and low for all other outcomes, with evidence being downgraded mainly because of imprecision and inconsistency. CONCLUSIONS/INTERPRETATION: Adherence to Nordic dietary patterns is associated with generally small important reductions in the risk of major CVD outcomes and diabetes, which are supported by similar reductions in LDL-cholesterol and other intermediate cardiometabolic risk factors. The available evidence provides a generally good indication of the likely benefits of Nordic dietary patterns in people with or at risk for diabetes. REGISTRATION: ClinicalTrials.gov NCT04094194. FUNDING: Diabetes and Nutrition Study Group of the EASD Clinical Practice.

Relationship between psychopathic traits and performance on the Mini Social Cognition and Emotional Assessment in incarcerated males.

Psychopathy is a constellation of personality traits such as callousness, manipulativeness, and impulsivity, and these traits often co-occur with antisocial behavior. Researchers and clinicians have posited that these traits may be associated with impairments in orbitofrontal cortex functioning, but researchers have rarely assessed this using clinical neuropsychological assessments. In a sample of 87 male inmates in a county jail, this study examined the relationship between psychopathic traits and performance on the Mini Social Cognition and Emotional Assessment (Mini-SEA), an assessment of orbitofrontal cortex functioning. Psychopathy scores (total or factor) were not correlated with Mini-SEA performance. Potential reasons for our null findings and study limitations are discussed. PRACTITIONER POINTS: Psychopathic traits were not associated with performance on a neuropsychological measure assessing orbitofrontal cortex functioning. Deficits in OFC functioning observed in psychopathy may be different in nature, or less severe, than those observed in patients with frontotemporal dementia, who perform poorly on this measure.

Youth with Low Pre-injury Mental Health Symptoms Are at a Higher Risk for Symptoms Following Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a growing public health concern, and it is a common injury amongst children and adolescents. Existing evidence suggests that mTBI in youth may be related to both externalizing and internalizing symptoms. However, many existing studies fail to control for pre-injury symptoms or consider the potential interaction between mTBI and pre-injury symptom levels. The current study employed data from a longitudinal sample (N = 1,803) of youth from the Project on Human Development in Chicago Neighborhoods to assess the interaction between pre-injury externalizing and internalizing symptoms and outcomes following mTBI in youth. The results showed, contrary to our expectations, that participants with lower pre-injury symptoms were at a greater risk for increased psychopathology following mTBI, compared to participants with higher pre-injury symptoms and non-injured participants. Potential explanations for the results and implications are discussed.

Feasibility and Acceptability of a Group Counseling Intervention for Opioid Use Disorder: An Exploratory Study.

The goal of the current exploratory study was to examine the feasibility and acceptability of an evidence-based group counseling intervention for individuals with opioid use disorders (OUD) reporting mental health issues and using medications for OUD. The intervention combines motivational interviewing and cognitive-behavioral therapy. Qualitative research methodology, specifically focus group interviewing, with seven individuals was used to examine the feasibility and acceptability of the intervention. Qualitative analysis of the focus group yielded four themes: Intervention Format, Group Counseling Factors, Comorbid Mental Health Issues, and Counselor Factors. The intervention proposed was found to be acceptable and feasible for addressing OUD and co-occurring mental health conditions, specifically depression, anxiety, and stress. [Journal of Psychosocial Nursing and Mental Health Services, 60(6), 7-10.].

Feasibility and Acceptability of a Mindfulness-Based Relapse Prevention Intervention for Opioid Use Disorders.

In 2021, drug overdose deaths exceeded 100,000 for the first time in U.S. history, mostly attributable to opioid overdoses. Medications for opioid use disorders are considered the gold standard for treatment; however, treatment initiation and adherence remain a challenge. Mindfulness-based interventions show efficacy for substance use disorders, and peer support has been shown to improve treatment outcomes. The purpose of the current study was to examine the feasibility and acceptability of the Minds and Mentors Program. Enrollment, randomization, and retention rates were 36%, 49%, and 57%, respectively. Client satisfaction scores ranged from 84.4% to 100%. Approximately 64% of participants attended 10 of 12 treatment sessions, representing treatment adherence. Qualitative analysis revealed four main domains: Permission to Be Honest and Open, Applicability for Everyday Life, Hope Restored, and Changing the Way I Think. [Journal of Psychosocial Nursing and Mental Health Services, 60(3), 11-14.].

Neurocriminology: implications for the punishment, prediction and prevention of criminal behaviour.

Criminal behaviour and violence are increasingly viewed as worldwide public health problems. A growing body of knowledge shows that criminal behaviour has a neurobiological basis, and this has intensified judicial interest in the potential application of neuroscience to criminal law. It also gives rise to important questions. What are the implications of such application for predicting future criminal behaviour and protecting society? Can it be used to prevent violence? And what are the implications for the way offenders are punished?

Group versus individual format of intervention for aggressive children: Moderators and predictors of outcomes through 4 years after intervention.

This study originated in collaboration with Thomas Dishion because of concerns that a group format for aggressive children might dampen the effects of cognitive-behavioral intervention. Three hundred sixty aggressive preadolescent children were screened through teacher and parent ratings. Schools were randomized to receive either an individual or a group format of the child component of the same evidence-based program. The results indicate that there is variability in how group-based cognitive-behavioral intervention can affect aggressive children through a long 4-year follow-up after the end of the intervention. Aggressive children who have higher skin conductance reactivity (potentially an indicator of poorer emotion regulation) and who have a variant of the oxytocin receptor gene that may be associated with being hyperinvolved in social bonding have better outcomes in their teacher-rated externalizing behavior outcomes over time if they were seen individually rather than in groups. Analyses also indicated that higher levels of the group leaders' clinical skills predicted reduced externalizing behavior problems. Implications for group versus individual format of cognitive-behavioral interventions for aggressive children, and for intensive training for group therapists, informed by these results, are discussed.

Toward Tailored Interventions: Sympathetic and Parasympathetic Functioning Predicts Responses to an Intervention for Conduct Problems Delivered in Two Formats.

Coping Power is an evidence-based preventive intervention for youth with aggressive behavior problems that has traditionally been delivered in small group formats, but because of concerns about potentially diminished effects secondary to aggregation of high-risk youth, an individual format of Coping Power has been developed. The current study examined whether physiological characteristics of the child may provide information about which intervention delivery format works best for that individual. Indicators of sympathetic and parasympathetic nervous system functioning were examined in 360 fourth-grade children (65% male; 76.4% self-reported African-American) who were randomly assigned to Group Coping Power (GCP) or Individual Coping Power (ICP) (Lochman et al. 2015). Longitudinal assessments of teacher- and parent-reported proactive and reactive aggression were collected through a 1-year follow-up. For children with higher initial levels of aggression, those with lower parasympathetic functioning at pre-intervention showed greater reductions in teacher-rated proactive aggression in the ICP condition than the GCP condition. For children with high parasympathetic functioning, there was no differential effect of intervention format. Regardless of intervention format, youth with lower levels of sympathetic functioning at pre-intervention demonstrated greater reductions in teacher-rated proactive aggression. These findings suggest that physiological indicators may be worth considering in future studies examining which youth respond best to specific types of interventions.

Early life predictors of callous-unemotional and psychopathic traits.

Psychopathy is a disorder that occurs primarily in males. Offenders with psychopathic traits are responsible for a disproportionate amount of crime in society, particularly violent crime. Early childhood is a time when individual differences in empathy and guilt-key indicators of the construct of psychopathy-are first evident. A growing number of longitudinal studies have begun to investigate how factors in infancy and early childhood predict psychopathic-like traits in later childhood, adolescence, and adulthood. These studies have suggested that parenting styles during infancy (parental sensitivity, maternal harsh intrusion, commenting on the emotional state of the child) as well as attachment styles are predictive of later psychopathic-like traits. In addition, child characteristics such as temperament and the functioning of biological systems such as the autonomic nervous system and hypothalamic-pituitary-adrenal axis are predictive. Overall, studies have suggested that at least some of the origins of psychopathic traits are present in infancy and early childhood, which is consistent with the perspective of psychopathy as a neurodevelopmental disorder. A recent evolutionary-developmental model provides hypotheses regarding how psychopathy may develop and why it is more common in males than females. This model, and its implications for intervention, is discussed in the context of the longitudinal studies that have been conducted on psychopathy.

The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: A double-blind, randomized, controlled, acute feeding, equivalence trial.

AIM: To assess and compare the effect of small doses of fructose and allulose on postprandial blood glucose regulation in type 2 diabetes. METHODS: A double-blind, multiple-crossover, randomized, controlled, acute feeding, equivalence trial in 24 participants with type 2 diabetes was conducted. Each participant was randomly assigned six treatments separated by >1-week washouts. Treatments consisted of fructose or allulose at 0 g (control), 5 g or 10 g added to a 75-g glucose solution. A standard 75-g oral glucose tolerance test protocol was followed with blood samples at -30, 0, 30, 60, 90 and 120 minutes. The primary outcome measure was plasma glucose incremental area under the curve (iAUC). RESULTS: Allulose significantly reduced plasma glucose iAUC by 8% at 10 g compared with 0 g (717.4 ± 38.3 vs. 777.5 ± 39.9 mmol × min/L, P = 0.015) with a linear dose response gradient between the reduction in plasma glucose iAUC and dose (P = 0.016). Allulose also significantly reduced several related secondary and exploratory outcome measures at 5 g (plasma glucose absolute mean and total AUC) and 10 g (plasma glucose absolute mean, absolute and incremental maximum concentration [Cmax ], and total AUC) (P < .0125). There was no effect of fructose at any dose. Although allulose showed statistically significant reductions in plasma glucose iAUC compared with fructose at 5 g, 10 g and pooled doses, these reductions were within the pre-specified equivalence margins of ±20%. CONCLUSION: Allulose, but not fructose, led to modest reductions in the postprandial blood glucose response to oral glucose in individuals with type 2 diabetes. There is a need for long-term randomized trials to confirm the sustainability of these improvements.

Oxytocin Receptor Gene Variant Interacts with Intervention Delivery Format in Predicting Intervention Outcomes for Youth with Conduct Problems.

Coping Power is an evidence-based preventive intervention program for youth with aggressive behavior problems that has traditionally been delivered in small group formats. Because of concerns about iatrogenic effects secondary to aggregation of high risk youth, the current study examined whether genetic risk may moderate intervention outcome when youth were randomly assigned to group versus individual formats of an intervention. The oxytocin receptor gene (OXTR) has been associated with social behavior and may influence susceptibility to social reinforcement in general and deviant peer influence in particular. One variant of OXTR (rs2268493) was examined in 197 fourth-grade African-American children (64% male) who were randomly assigned to Group Coping Power or Individual Coping Power (Lochman et al. 2015). Longitudinal assessments of teacher- and parent-reported behavior were collected through a 1-year follow-up. Growth curve analyses revealed a genotype by delivery format interaction. Youth with the A/A genotype demonstrated reductions in externalizing problems over the course of the intervention regardless of intervention format. In contrast, carriers of the G allele receiving the group-based intervention showed little improvement during the intervention and a worsening of symptoms during the follow-up year, while those receiving the individual format demonstrated reductions in externalizing problems. Given the associations between this OXTR variant and social bonding, carriers of the G allele may be more sensitive to social rewards from deviant peers in the group setting. This study suggests that genetic factors may be useful in predicting which type of intervention will be most effective for a particular individual.

Autonomic functioning in reactive versus proactive aggression: The influential role of inconsistent parenting.

Research has consistently supported autonomic nervous system (ANS) functioning as a predictor of aggressive behavior in youth. Several studies have further examined how the functioning of the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS interact with environmental factors to predict behavioral outcomes. One factor that has yet to be studied in this context however, is parenting practices. Given that many interventions for externalizing behavior target parenting practices, such as increasing consistent discipline, it may be particularly important to assess whether parenting practices interact with SNS and PNS functioning in the child to influence risk for aggressive behavior. Therefore, the current study addressed this question by examining inconsistent discipline as a moderator of the relationship between baseline SNS versus PNS activity and reactive versus proactive aggression. Data were collected from a sample of fourth graders identified as at-risk for aggression (N = 188). Results indicated that baseline SNS activity was positively related to proactive aggression under high levels of inconsistent discipline, but negatively related to proactive aggression under very low levels of inconsistent discipline. Baseline PNS activity was negatively associated with reactive aggression under low levels of inconsistent discipline. No main effects were found for SNS or PNS functioning and either form of aggression, emphasizing the importance of taking a biosocial approach to examining the predictors of aggressive behavior in at-risk youth. Results from this study help to better understand the circumstances under which children are most likely to exhibit reactive versus proactive aggression, better informing targeted prevention and treatment.

Neurocognitive characteristics of youth with noncomorbid and comorbid forms of conduct disorder and attention deficit hyperactivity disorder.

OBJECTIVE: Studies investigating neurocognitive deficits in youth with conduct disorder (CD) and attention deficit hyperactivity disorder (ADHD) are often confounded by the high rates of comorbidity between the two. METHOD: Neurocognitive functioning was examined in three diagnostic groups (ADHD only, CD only, comorbid ADHD and CD) matched by age, sex, IQ, and medication status (n=28-32 per group). RESULTS: No significant differences emerged between the diagnostic groups on measures of risk-taking or response inhibition. Children with CD performed better on a measure of spatial planning than those with comorbid ADHD and CD, and dimensional analyses in the full sample (n=265) revealed a small association between ADHD symptoms and poorer spatial planning. CONCLUSION: These results suggest that deficits in spatial planning may be more pronounced in individuals with ADHD, but that the neurocognitive functioning of youth with noncomorbid and comorbid CD and ADHD are largely similar.

Agreement Between Parent- and Self-Reports of Psychopathic Traits and Externalizing Behaviors in a Clinical Sample.

A number of studies have identified discrepancies in informant ratings of externalizing behaviors in youth, but it is unclear whether similar discrepancies exist between informants when rating psychopathic traits. In this study, we examined parent-child agreement on ratings of both psychopathic traits and externalizing behaviors, and examined the factors that influence agreement in both of these domains. A total of 282 children between 7 and 16 years (M = 10.60 years, SD = 1.91) from an outpatient child psychiatric clinic participated in this study. Our findings revealed low levels of parent-child agreement on these measures (ICC values ranging from .02 to .30 for psychopathic traits; ICC values ranging from .09 to .30 for externalizing behaviors). In addition, our findings did not support the moderating effects of child's age, gender, clinical diagnosis, informant, and parental conflict on the relationship between parent- and child-ratings of psychopathic traits and externalizing behaviors. Further research is needed to better understand how parents and child reports of child's externalizing behaviors and psychopathic traits are similar and/or different from one another and factors that influence these agreements.

Hypothalamic pituitary adrenal activity and autonomic nervous system arousal predict developmental trajectories of children's comorbid behavior problems.

The combined effects of hypothalamic-pituitary-adrenal (HPA) axis activity and autonomic nervous system (ANS) arousal were examined on developmental trajectories of children's comorbid internalizing and externalizing problems. Participants were 394 urban dwelling, primarily African American, youth (50% male, age 11-12 years). Parent-reported child behavior problems were obtained initially, 3, 6, and 12 months later. Saliva samples (collected at the initial assessment) were assayed for cortisol (HPA) and alpha-amylase (ANS). Cross-domain latent class growth analysis identified a stable comorbid trajectory and four other distinct short-term developmental trajectories of internalizing and externalizing behavior problems. ANS arousal was negatively associated with the probability of stable comorbidity, but only among youth who also had high levels of HPA axis activity. Findings underscore the predictive value of the interaction of HPA axis activity and ANS arousal in differentiating children with stable comorbidity and have important implications for etiological theories and treatment outcome research.

The methods and baseline characteristics of a multi-site randomized controlled trial evaluating mindfulness-based relapse prevention in conjunction with peer support to improve adherence to medications for opioid use disorders.

Introduction: Medications for opioid use disorders (MOUD) remain the gold standard for treating OUD, but treatment initiation and adherence remain challenging. Exclusive utilization of pharmacotherapy as a treatment modality for OUD is sub-optimal, and a combination of psychotherapies and pharmacotherapies is recommended. General trends indicate the benefits of peer mentoring and MBRP separately. Therefore, we hypothesize that the combined effect of MBRP and Peer mentoring will produce synergistic improvements in MOUD adherence compared to an enhanced twelve-step facilitation (TSF). Methods: This paper describes the methods and baseline characteristics of a multi-site randomized controlled trial evaluating the effectiveness of a combination of MBRP and peer support (MiMP) compared to an enhanced TSF in improving adherence to MOUD. Both MiMP and TSF are 12-week manualized protocols that utilize licensed therapists. The interventions are delivered in weekly group sessions that last about 75-90 minutes per session. The primary outcome is MOUD adherence. Secondary and exploratory outcomes include relapse, cravings, depression, anxiety, stress, quality of life, and pain catastrophizing. Results: The participants' ages ranged from 21 years to 77 years, with a mean age of 44.5 (SD ± 11.5 years). There was an almost equal distribution of gender and place of residence. Overall, 51.9% (n=54) of participants identified as female and 48.1% (n=50) were male. Similarly, 51.9% (n=54) of participants resided in urban areas, while 48.1% (n=50) resided in rural areas. Participants identified as either black or white, with over three-quarters identifying as white (77.9%, n= 81) and 22.1% (n= 23) as black. Most participants randomized to the 12-step facilitation group were white (93.1%). Relationships and employment status were well distributed between categories. Over half of the participants reported some college or higher education. Over 90% of the participants made less than $75,000 per year. Some participants indicated that they had both public and private health insurance. Discussion and conclusion: This study is innovative in several ways including combining MBRP and peer support, addressing comorbid mental health issues among individuals with OUD, utilizing manualized protocols, and evaluating of both physiological and self-reported measures in assessing cortisol reactivity as a predictor of relapse and treatment outcomes.

Integration of epidemiological and blood biomarker analysis links haem iron intake to increased type 2 diabetes risk.

Dietary haem iron intake is linked to an increased risk of type 2 diabetes (T2D), but the underlying plasma biomarkers are not well understood. We analysed data from 204,615 participants (79% females) in three large US cohorts over up to 36 years, examining the associations between iron intake and T2D risk. We also assessed plasma metabolic biomarkers and metabolomic profiles in subsets of 37,544 (82% females) and 9,024 (84% females) participants, respectively. Here we show that haem iron intake but not non-haem iron is associated with a higher T2D risk, with a multivariable-adjusted hazard ratio of 1.26 (95% confidence interval 1.20-1.33; P for trend <0.001) comparing the highest to the lowest quintiles. Haem iron accounts for significant proportions of the T2D risk linked to unprocessed red meat and specific dietary patterns. Increased haem iron intake correlates with unfavourable plasma profiles of insulinaemia, lipids, inflammation and T2D-linked metabolites. We also identify metabolites, including L-valine and uric acid, potentially mediating the haem iron-T2D relationship, highlighting their pivotal role in T2D pathogenesis.

Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants.

BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.