Cumulative intake of artificially sweetened and sugar-sweetened beverages and risk of incident type 2 diabetes in young adults: the Coronary Artery Risk Development In Young Adults (CARDIA) Study Kristin M Hirahatake,1 David R Jacobs, Jr.,2 James M Shikany,2,3 Luohua Jiang,1 Nathan D Wong,1,4 Lyn M Steffen,1 and Andrew O Odegaard1 1Department of Epidemiology, School of Medicine, University of California, Irvine, CA, USA; 2Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, MN, USA; 3Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, AL, USA; and 4Heart Disease Prevention Program, Department of Medicine, University of California, Irvine, CA, USA Abstract Background: Epidemiological evidence has demonstrated a positive association between artificially sweetened beverage (ASB) and sugar-sweetened beverage (SSB) consumption and type 2 diabetes (T2D) risk. However, research informing this topic in young adults is limited. Objective: This study examined the association between ASB, SSB, and total sweetened beverage (TSB; combined ASB and SSB) consumption and T2D risk in young adults. Results: During the 30-y follow-up period, 680 participants developed T2D. ASB consumption was associated with a 12% greater risk of T2D per serving/day (HR 1.12, 95% CI 1.04–1.20) in a model adjusted for lifestyle factors, diet quality, and dieting behavior. Further adjustments for baseline BMI (HR 1.07, 95% CI 0.99–1.14) and weight change during follow-up (HR 1.04, 95% CI 0.97–1.12) attenuated the association. SSB and TSB consumption as continuous variables per 1 serving/day of intake were associated with 6% and 5% increased risks of T2D, respectively (HRSSB 1.06, 95% CI 1.01–1.10; HRTSB 1.05, 95% CI 1.01–1.09), in the model accounting for lifestyle factors, dieting behavior, baseline BMI, and weight change. Results were consistent when the exposures were modeled in categories of consumption and quintiles. Conclusions: In young adults, long-term ASB, SSB, and TSB consumption were associated with increased risks of T2D. However, the estimates for ASB were attenuated when accounting for weight changes. Introduction For several decades, the rise in obesity and the prevalance of type 2 diabetes (T2D) in the United States closely paralleled the rise in both artificially sweetened beverage (ASB) and sugar-sweetened beverage (SSB) consumption (1). Consequently, lowering SSB intakes has become an important focus of public health nutrition efforts, and recent reports indicate that SSB intake in the United States is declining, while water consumption is rising (2). Consumption of ASBs, often marketed as healthy alternatives to SSBs, has come under scrutiny due to research findings and long-term safety concerns (3). Notably, both ASB and SSB intake trends vary among different age and sociodemographic groups (2–4). Although the body of evidence supports a positive association between SSB consumption and obesity and T2D risk (5–7), there are methodological limitations of the experimental studies, and a closer examination of observational studies suggests potential publication biases (8, 9). At the same time, despite the promotion of ASBs as healthy, sugar-free, low-calorie alternatives to SSBs (10, 11), their role in weight management remains inconclusive, and evidence on the metabolic and health effects of ASB consumption over time is limited (12–14). Furthermore, evidence from prospective, observational studies suggests a positive association between ASB consumption and long-term cardiometabolic risk, but the results have been less consistent than the SSB–T2D relationship, and reverse causation, publication biases, and residual confounding have been suggested as explanatory factors (7, 12, 13). A recent scientific advisory report from the American Heart Association suggested that consuming ASBs may be a useful temporary replacement strategy to reduce SSB intake, but the optimal long-term choice was to avoid both beverages; this implies that both ASB and SSB have similar, negative roles in cardiometabolic health, despite a lack of direct evidence examining the relationship of the combined intake of the beverages with outcomes (3). Additionally, the observational studies on this topic have largely examined middle-aged and older adults, while evidence is lacking for how sweetened beverage consumption habits relate to T2D risks beginning in early adulthood. To address these gaps, we examined the relationships between ASB, SSB, and total sweetened beverage (TSB; ASB and SSB intake combined) consumption over time and T2D risk in young adult men and women from the Coronary Artery Risk Development In Young Adults (CARDIA) study. Methods Study population The CARDIA study is a prospective, multicenter cohort study designed to investigate the development and determinants of cardiovascular disease and its associated risk factors in young adults. Briefly, 5115 Black and White men and women aged 18–30 years were recruited between 1985–1986 from 4 US cities: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California. Participant enrollment targeted balances among age, race, sex, and educational attainment. The initial examination included standardized measures of known cardiovascular risk factors, as well as psychosocial, dietary, and exercise-related characteristics. Reexamination occurred at 2, 5, 7, 10, 15, 20, 25, and 30 years after baseline, with retention of 91%, 86%, 81%, 79%, 74%, 72%, 72%, and 71% of the surviving cohort, respectively. The CARDIA study was approved by the institutional review board at each field center, and informed consent was obtained from all participants prior to enrollment (15). Participants with a diagnosis of diabetes at baseline (n = 34), missing baseline diabetes status data (n = 88), or missing baseline dietary data (n = 4) were excluded from this analysis. Additionally, individuals who only participated in the baseline visit and had no follow-up data (n = 152) and individuals with extreme energy intakes [<600 kcal/day or >6000 kcal/day for women (n =53) and <800 kcal/day or >8000 kcal/day for men (n = 64)] were also excluded. The proportion of missing data for other pertinent covariates was low (<1%); missing values were imputed by sex and race subgroup to the median value for continuous variables (BMI, alcohol intake, physical activity) and to the most frequent categorical value for multichotomous variables (smoking status) (16). The final study sample for this analysis included 4719 Black and White young adult men and women. Beverage consumption Dietary intake was assessed at baseline (Year 0) and at Years 7 and 20 using the CARDIA Diet History: an interviewer-administered, validated dietary assessment instrument consisting of a short questionnaire on general dietary practices, followed by a comprehensive questionnaire about typical intake of foods, using the previous 1 month as a reference for recall (17). Briefly, interviewers asked study participants open-ended questions about dietary consumption in the past month within 100 food categories, referencing 1609 separate food items in Years 0 and 7 and several thousand separate food items in Year 20. Follow-up questions for selected foods concerned serving size, frequency of consumption, and common additions to these foods. Provision was made for reporting foods not found in the food frequency list. Diet history data were coded by the University of Minnesota Nutrition Coordinating Center and categorized into 166 food groups. As done in previous CARDIA studies (18, 19), we further collapsed these groups to define SSBs as sugar-sweetened soft drinks and fruit drinks and ASBs as soft drinks and fruit drinks sweetened with non-nutritive (non-caloric) sweeteners, both measured as the total number of 8-ounce servings per day. We also calculated combined TSB intake as the sum of SSB and ASB intake at each time point. The purpose of combining SSB and ASB was to provide an exposure variable that directly tested the most recent scientific statement from the American Heart Association on low-calorie sweetened beverages, which suggested that the hypothesized optimum sweetened beverage intake was essentially no intake (3). Though the potential underlying putative mechanisms between ASB and SSB intakes with cardiometabolic health likely differ, a simple adjustment of the other beverage type may not completely account for the potential confounding of crossover consumption of SSBs to ASBs, or vice versa, that could occur over time. To examine the relationship between beverage intake over time and T2D risk, we calculated a cumulative, average value of ASB, SSB, and TSB consumption for each participant using dietary data from Years 0, 7, and 20. For participants with follow-up times >0 and 7 years, we used beverage intake from Y0 only. For participants with follow-up times >7 and 20 years, cumulative, average beverage intakes from Y0 and Y7 data were used. For participants with follow-up time >20 years, the cumulative, average of beverage intakes at Y0, Y7, and Y20 was used. We used this approach to ensure that only beverage consumption prior to incident T2D was included in our analysis. Cumulative averages were calculated based on available data; individuals without repeated measures of diet were assigned their baseline beverage intake level. Incident type 2 diabetes mellitus Diabetes status was assessed at examination Years 0, 7, 10, 15, 20, 25, and 30. All blood samples were drawn and