28 April 2022 In Diabetes

AIMS/HYPOTHESIS: The aim of this study was to evaluate the prospective association between baseline and 9 year change in alcohol consumption and long-term risk of diabetes and whether these associations might be modified by sex and/or BMI.

METHODS: We conducted a prospective analysis of 12,042 Atherosclerosis Risk in Communities (ARIC) study participants without prevalent diabetes (55% women, 78% white, mean age 54 years). Alcohol consumption was assessed at visit 1 (1987-1989) and visit 4 (1996-1998). We used Cox models to estimate hazard ratios for diabetes risk by baseline drinking categories and change in alcohol consumption, stratified by sex and obesity status.

RESULTS: During a median follow-up of 21 years, there were 3795 incident cases of diabetes. Among women, consuming 8-14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.75, 95% CI 0.58, 0.96) compared with current drinkers consuming ≤1 drink/week. Among men, consuming 8-14 drinks/week was associated with a borderline significant lower risk of diabetes (HR 0.84, 95% CI 0.70, 1.00) and consuming >14 drinks/week was associated with a significantly lower risk of diabetes (HR 0.81, 95% CI 0.67, 0.97) (p(interaction) < 0.01 for sex). For both sexes, among current drinkers, there was a significant decreasing trend in diabetes risk as the alcohol consumption increased. The association was modified by BMI (p(interaction) = 0.042 for women, p(interaction) < 0.001 for men). In women, the inverse association was only seen among overweight and obese participants. In men, the inverse association was more pronounced among obese participants. On average, drinking status did not change substantially over the 9 year period. For men with alcohol intake ≥7 drinks/week at baseline, decreasing alcohol intake was associated with higher risk of diabetes (HR per daily drink decrease 1.12, 95% CI 1.02, 1.23).

CONCLUSIONS/INTERPRETATION: In this community-based population, there was an inverse association between alcohol consumption and diabetes risk. The amount of the alcohol consumption associated with lower risk was different in women and men, and the association was more pronounced among participants with higher BMI.

28 April 2022 In Dementia

BACKGROUND: Dementia indicates a significant disease burden worldwide with increased population aging. This study aimed to investigate the impact of alcohol consumption on the risk of cognitive impairment in older adults.

METHODS: Participants >/= 60 years were administered the Digit Symbol Substitution Test (DSST) to evaluate cognitive function in National Health and Nutrition Examination Survey (NHANES) cycles from 1999 to 2002 and 2011 to 2014 for enrollment in the present study. Participants were categorized into non-drinker, drinker, and heavy drinker groups. Logistic regression analyses were performed to explore associations between cognitive impairment and alcohol consumption.

RESULTS: Multivariate analysis showed that older adults, men, people from minority races, persons with lower education or income levels, social difficulties, hypertension, or chronic kidney disease were significantly associated with a higher risk of cognitive impairment (all p < 0.05). In the young old (60-69 years), heavy amount of alcohol drinking was significantly associated with lower risk of cognitive impairment compared with drinkers [adjusted odds ratio (aOR): 0.280, 95% Confidence interval (CI) 0.095-0.826]. But in the middle old persons (>/= 70 years), heavy alcohol drinking was associated with higher risk of cognitive impairment (aOR: 2.929, 95% CI 0.624-13.74).

CONCLUSIONS: Our study demonstrated that light to heavy drinking was associated with lower risk of cognitive impairment in participants aged between 60 and 69 years, but caution is needed in the middle old people with heavy alcohol drinking.

28 April 2022 In Cardiovascular System

IMPORTANCE: Observational studies have consistently proposed cardiovascular benefits associated with light alcohol consumption, while recent genetic analyses (ie, mendelian randomization studies) have suggested a possible causal link between alcohol intake and increased risk of cardiovascular disease. However, traditional approaches to genetic epidemiology assume a linear association and thus have not fully evaluated dose-response estimates of risk across different levels of alcohol intake.

OBJECTIVES: To assess the association of habitual alcohol intake with cardiovascular disease risk and to evaluate the direction and relative magnitude of cardiovascular risk associated with different amounts of alcohol consumption.

DESIGN, SETTING, and PARTICIPANTS: This cohort study used the UK Biobank (2006-2010, follow-up until 2016) to examine confounding in epidemiologic associations between alcohol intake and cardiovascular diseases. Using both traditional (ie, linear) and nonlinear mendelian randomization, potential associations between alcohol consumption and cardiovascular diseases (eg, hypertension and coronary artery disease) as well as corresponding association shapes were assessed. Data analysis was conducted from July 2019 to January 2022.

EXPOSURES: Genetic predisposition to alcohol intake.

MAIN OUTCOMES AND MEASURES: The association between alcohol consumption and cardiovascular diseases, including hypertension, coronary artery disease, myocardial infarction, stroke, heart failure, and atrial fibrillation.

RESULTS: This study included 371463 participants (mean [SD] age, 57.0 [7.9] years; 172400 [46%] men), who consumed a mean (SD) 9.2 (10.6) standard drinks per week. Overall, 121708 participants (33%) had hypertension. Light to moderate alcohol consumption was associated with healthier lifestyle factors, adjustment for which attenuated the cardioprotective epidemiologic associations with modest intake. In linear mendelian randomization analyses, a 1-SD increase in genetically predicted alcohol consumption was associated with 1.3-fold (95% CI, 1.2-1.4) higher risk of hypertension (P < .001) and 1.4-fold (95% CI, 1.1-1.8) higher risk of coronary artery disease (P = .006). Nonlinear mendelian randomization analyses suggested nonlinear associations between alcohol consumption and both hypertension and coronary artery disease: light alcohol intake was associated with minimal increases in cardiovascular risk, whereas heavier consumption was associated with exponential increases in risk of both clinical and subclinical cardiovascular disease.

CONCLUSIONS and RELEVANCE: In this cohort study, coincident, favorable lifestyle factors attenuated the observational benefits of modest alcohol intake. Genetic epidemiology suggested that alcohol consumption of all amounts was associated with increased cardiovascular risk, but marked risk differences exist across levels of intake, including those accepted by current national guidelines.

22 March 2022 In Liver Disease

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk.

METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (>/=80 g/day (men), >/=50 g/day (women), for >/=10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC).

RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 +/- 0.06 vs. 0.61 +/- 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption.

CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions.

LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

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