Steven Bell

Alcohol Consumption and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of More Than 1.9 Million Individuals From 38 Observational Studies

OBJECTIVE Observational studies indicate that moderate levels of alcohol consumption may reduce the risk of type 2 diabetes. In addition to providing an updated summary of the existing literature, this meta-analysis explored whether reductions in risk may be the product of misclassification bias. RESEARCH DESIGN AND METHODS A systematic search was undertaken, identifying studies that reported a temporal association between alcohol consumption and the risk of type 2 diabetes. No restrictions were placed upon the language or date of publication. Non-English publications were, where necessary, translated using online translation tools. Models were constructed using fractional polynomial regression to determine the best-fitting dose-response relationship between alcohol intake and type 2 diabetes, with a priori testing of sex and referent group interactions. RESULTS Thirty-eight studies met the selection criteria, representing 1,902,605 participants and 125,926 cases of type 2 diabetes. A conventional noncurrent drinking category was reported by 33 studies, while five reported a never-drinking category. Relative to combined abstainers, reductions in the risk of type 2 diabetes were present at all levels of alcohol intake <63 g/day, with risks increasing above this threshold. Peak risk reduction was present between 10–14 g/day at an 18% decrease in hazards. Stratification of available data revealed that reductions in risk may be specific to women only and absent in studies that adopted a never-drinking abstention category or sampled an Asian population region. CONCLUSIONS Reductions in risk among moderate alcohol drinkers may be confined to women and non-Asian populations. Although based on a minority of studies, there is also the possibility that reductions in risk may have been overestimated by studies using a referent group contaminated by less healthy former drinkers.

Alcohol consumption and cognitive decline in early old age

Objective: To examine the association between alcohol consumption in midlife and subsequent cognitive decline. Methods: Data are from 5,054 men and 2,099 women from the Whitehall II cohort study with a mean age of 56 years (range 44–69 years) at first cognitive assessment. Alcohol consumption was assessed 3 times in the 10 years preceding the first cognitive assessment (1997–1999). Cognitive tests were repeated in 2002–2004 and 2007–2009. The cognitive test battery included 4 tests assessing memory and executive function; a global cognitive score summarized performances across these tests. Linear mixed models were used to assess the association between alcohol consumption and cognitive decline, expressed as z scores (mean = 0, SD = 1). Results: In men, there were no differences in cognitive decline among alcohol abstainers, quitters, and light or moderate alcohol drinkers (<20 g/d). However, alcohol consumption ≥36 g/d was associated with faster decline in all cognitive domains compared with consumption between 0.1 and 19.9 g/d: mean difference (95% confidence interval) in 10-year decline in the global cognitive score = −0.10 (−0.16, −0.04), executive function = −0.06 (−0.12, 0.00), and memory = −0.16 (−0.26, −0.05). In women, compared with those drinking 0.1 to 9.9 g/d of alcohol, 10-year abstainers showed faster decline in the global cognitive score (−0.21 [−0.37, −0.04]) and executive function (−0.17 [−0.32, −0.01]). Conclusions: Excessive alcohol consumption in men (≥36 g/d) was associated with faster cognitive decline compared with light to moderate alcohol consumption.

Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records

Abstract Objectives To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption. Design Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years). Setting CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). Participants 1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline. Main outcome measures 12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm. Results 114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00). Conclusions Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary. Registration clinicaltrails.gov (NCT01864031).

Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis

Summary Background Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. Methods In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p≤5 × 10−8) were tested for replication in an independent GWAS of 30 770 cases and 286 913 controls, followed by a joint analysis of the discovery and replication stages. We did gene annotation, pathway, and gene-set-enrichment analyses and studied the genetic correlations between restless legs syndrome and traits of interest. Findings We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1·92, 95% CI 1·85–1·99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1). Interpretation Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations. Funding Deutsche Forschungsgemeinschaft, Helmholtz Zentrum München–Deutsches Forschungszentrum für Gesundheit und Umwelt, National Research Institutions, NHS Blood and Transplant, National Institute for Health Research, British Heart Foundation, European Commission, European Research Council, National Institutes of Health, National Institute of Neurological Disorders and Stroke, NIH Research Cambridge Biomedical Research Centre, and UK Medical Research Council.

Reasons why people change their alcohol consumption in later life: findings from the Whitehall II Cohort Study.

Purpose Harmful alcohol consumption among the ageing population is an important public health issue. Very few studies ask drinkers why they change their consumption in later life. The aim of this paper was to determine whether a group of people aged over 60 years increased or decreased their alcohol consumption over the past decade and to determine the reasons for their change. We also examined whether the responses varied by age, sex and socio-economic position (SEP). Subjects and Methods Data were taken from 6,011 participants (4,310 men, 1,701 women, age range 61 to 85 years) who completed questionnaires at phase 11 (2012-2013) of the Whitehall II Cohort Study. Results Over half the study members reported a change in alcohol consumption over the past decade (40% decreased, 11% increased). The most common reasons given for decreases were as a health precaution and fewer social occasions. Common reasons for increases were more social occasions and fewer responsibilities. The lowest SEP group was less likely to increase consumption compared to high SEP (RR 0.57, 95% CI 0.40 to 0.81). Women were more likely to increase consumption in response to stress/depression than men (RR1.53, 95% CI 1.04 to 2.25). Compared to high SEP, the lowest SEP group was less likely to reduce as a health precaution (RR 0.61, 95% CI 0.38 to 0.76). Conclusions Alcohol consumption in late life is not fixed. Reasons for change vary by age, sex and SEP. Such information could be used to tailor intervention strategies to reduce harmful consumption.

Dose-Response Association Between Psychological Distress and Risk of Completed Suicide in the General Population

Elevated suicide rates in people with clinical depression, as indexed by hospitalizations or use of psychiatric outpatient services, are well documented. However, the association between depression across the full range of severity and subsequent suicide risk is unknown. With single-cohort studies insufficiently powered to examine this relation, to our knowledge, we provide the first pooling of individual-level data from a series of large general population–based cohort studies.

Association of Systemic Inflammation With Risk of Completed Suicide in the General Population.

Association of Systemic Inflammation With Risk of Completed Suicide in the General Population There is a growing prima facie case for inflammation being associated with suicide. In cohort studies,1 elevated levels of inflammatory markers have been linked to the future occurrence of depression, a known risk factor for suicide. In psychiatric patients, inflammation is positively associated with the intensity of self-reported suicidal ideation,2 and those who commit suicide have higher cytokine levels post mortem relative to control patients.3 Furthermore, individuals with asthma, a condition characterized by inflammation, experience higher rates of suicide mortality than their nonatopic counterparts.4 While these various lines of evidence may implicate inflammation in the pathophysiology of suicide, there has been no prospective examination of the link between inflammation and future suicide events.

Ten-year alcohol consumption typologies and trajectories of C-reactive protein, interleukin-6 and interleukin-1 receptor antagonist over the following 12 years: a prospective cohort study

Moderate alcohol consumption is thought to confer cardiometabolic protective effects. Inflammatory pathways are hypothesized to partly underlie this association.

Drinking Pattern, Abstention and Problem Drinking as Risk Factors for Depressive Symptoms: Evidence from Three Urban Eastern European Populations

Purpose To examine whether the frequency and amount of alcohol consumed in binge drinking sessions, total annual volume of alcohol consumed, problem drinking and abstaining from alcohol are associated with depressive symptoms in Eastern Europe. Subjects and Methods Cross-sectional data from a total of 24,381 participants from general population samples of the Czech Republic (N = 7,601), Russia (N = 6,908) and Poland (N = 9,872) aged 45–69 years in 2002–2005. Depressive symptoms were defined as ≥16 points on the Centre for Epidemiological Studies – Depression (CES-D) scale. Several alcohol related measures were derived using responses from the graduated frequency questionnaire. Binge drinking was defined at several sex-specific thresholds (ranging from 60+ to 140+ g of ethanol) and two frequencies (at least monthly or weekly). Total annual alcohol intake in grams was also extracted. Problem drinking was defined as ≥2 positive answers on the CAGE questionnaire. Results Problem drinking was consistently associated with approximately a 2-fold increase in odds of depressive symptoms across all countries and in both sexes. Abstaining from alcohol was typically associated with increased odds of depressive symptoms. Analyses separating lifelong abstainers and former drinkers in the Russian cohort revealed that this increased odds was driven by former drinkers. Amongst men, heavy frequent binge drinking was associated with increased odds of depressive symptoms in the Czech Republic and Poland. In women, heavy infrequent binge drinking was associated with increased odds of depressive symptoms in Russia and Poland. Only in Polish men was higher annual volume of alcohol intake associated with increased odds of depressive symptoms. Conclusion Abstaining from alcohol and problem drinking were associated with increased odds of depressive symptoms in these Eastern European populations. Annual volume of alcohol intake as well as frequency and amount of alcohol consumed in a binge drinking session were less consistently associated with depressive symptoms.

Twenty‐Five‐Year Alcohol Consumption Trajectories and Their Association With Arterial Aging: A Prospective Cohort Study

Background Emerging evidence suggests that arterial stiffness, an important marker of cardiovascular health, is associated with alcohol consumption. However, the role of longer‐term consumption patterns in the progression of arterial stiffness over time remains unclear. A longitudinal cohort design was used to evaluate the association between alcohol consumption over 25 years and subsequent changes in arterial stiffness. Methods and Results Data (N=3869; 73% male) were drawn from the Whitehall II cohort study of British civil servants, in which participants completed repeat pulse wave velocity assessments of arterial stiffness across a 4‐ to 5‐year interval. Repeated alcohol intake measurements were used to categorize participants into alcohol consumer types, accounting for longitudinal variability in consumption. Sex‐stratified linear mixed‐effects modeling was used to investigate whether drinker types differed in their relationship to pulse wave velocity and its progression over time. Males with consistent long‐term heavy intake >112 g of ethanol/week had significantly higher baseline pulse wave velocity (b=0.26 m/s; P=0.045) than those who drank consistently moderately (1–112 g of ethanol/week). Male former drinkers showed significantly greater increases in arterial stiffness longitudinally compared to consistently moderate drinkers (b=0.11 m/s; P=0.009). All associations were nonsignificant for females after adjustment for body mass index, heart rate, mean arterial pressure, diabetes mellitus, high‐density lipoprotein, and triglycerides. Conclusions This work demonstrates that consistently heavy alcohol consumption is associated with higher cardiovascular risk, especially among males, and also provides new insights into the potential impact of changes in drinking levels over time. It discusses the additional insights possible when capturing longitudinal consumption patterns in lieu of reliance on recent intake alone. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02663791.