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By Husham Syed-Mohammed Richard Grucza, Andrew Plunk, Laura Bierut, Pamela Hipp • GGT is a glycoprotein enzyme involved in counteracting oxidative stress • Increase in serum levels with repeated excessive alcohol consumption • Asparate and Alanine Aminotransferase are liver enzymes involved in amino acid metabolism. • Used clinically as indicators of liver cell injury • Commonly tested in clinical settings in liver panel tests • Studies have linked high GGT levels in risk prediction of type 2 diabetes, cardiovascular events, chronic kidney disease, and cancer • Numerous studies have associated GGT with all-cause mortality independent of alcohol use • Is GGT a more sensitive indicator of alcohol drinking patterns than ALT or AST? • Do drinking patterns impact GGT levels over and above total alcohol intake? • How are alcohol drinking behaviors associated with all-cause mortality? • How does GGT influence mortality at different levels of drinking? • National Health and Nutritional Examination Survey • Designed to assess the health and nutritional status of adults and children in the United States • Began in early 1960’s and data is still being currently collected • Combines interviews, physical examinations, and lab tests • N=16,811 • Data from five administrations of NHANES (1999-2008) • All past-year drinkers 21 years and older • Drinkers were described as those having at least 12 drinks in the past year • Whites, Hispanics, and Blacks • Compared the association of binge-drinking and non binge-drinking behaviors with GGT, AST, and ALT serum levels • Binge-drinking was described as having five or more drinks per drinking episode • “Moderate-drinking” was described as having four or less drinks per drinking episode GGT is More Sensitive to Binge-Drinking and ModerateDrinking Patterns Regression Coefficient 2.5000 GGT AST ALT Binge Drinking Days Per Week 2.0000 1.5000 1.0000 Moderate Drinking Days per Week 0.5000 0.0000 Male Female Male Female Male Liver Enzyme (Enzyme levels analyzed as T-Scores) FIGURE 1. Analysis were controlled for age, smoking behaviors, race, and weight to height ratio. Female • Compared association of serum GGT levels with different drinking patterns in different categories of total alcohol consumption • This was to test our hypothesis if drinking patterns impact GGT levels over and above total alcohol intake? Total Alcohol Consumption and Binge Drinking Increase GGT Levels 59 58 Serum GGT Levels (T-Score) 57 56 Average Weekly Consumption of Alcohol 55 54 0-2 drinks per week 2-6 drinks per week 53 6-14 drinks per week 14-192 drinks per week 52 51 50 Zero Light Med. Heavy Binge-Drinking Behavior FIGURE 2. Zero=zero days in year binge drinking, light=1-12 days in year binge drinking, med=13-52 days in year binge-drinking, heavy=53 or more days in year binge drinking. • N=6,834 • Used the same inclusion criteria as previous study • Survival Analysis: Mortality predicted from alcohol drinking patterns • Survival Analysis: Mortality predicted from GGT serum levels in different binge-drinking categories Effects of Drinking Patterns on Mortality 1.3 1.2 Hazard Ratio 1.1 1 Male Hazard Ratios 0.9 0.8 Female Hazard Ratios 0.7 Moderate Drinks Per Week Binge Drinks Per Week Categories Figure 3. Controls for this analysis included age, race, smoking behavior, poverty index, and waist to hip ratio. GGT is More Predictive of Mortality in Heavy Binge-Drinkers 1.6 1.5 Hazard Ratio 1.4 1.3 Male Hazard Ratios 1.2 Female Hazard Ratios 1.1 1 0 Days in Year Binge Drinking 1-12 Days in Year Binge Drinking 13-52 Days in Year Binge Drinking Binge Drinking Category Figure 4 The analysis was controlled for age, race, smoking behavior, poverty index, and waist to hip ratio. • GGT serum levels are the most sensitive liver enzyme associated with alcohol consumption • Both the amount of drinking and the pattern of drinking effects GGT levels • Binge-drinking behaviors strongly predict mortality, while moderate-drinking behaviors do not seem to have an effect • The association between GGT and mortality may be stronger in heavier drinkers • Thank you everyone who helped with the research this summer: – ARTSS Internship program – Richard Grucza – Pamela Hipp – Andrew Plunk – Laura Bierut