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The Association Between Dietary Choline and Betaine with the Risk

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The Association Between Dietary Choline and Betaine with the Risk Diabetes Care 1 The Association Between Dietary Daniel T. Dibaba,1,2 Karen C. Johnson,1,2 Anna M. Kucharska-Newton,3,4 Choline and Betaine With the Risk Katie Meyer,5 Steven H. Zeisel,6 and Aurelian Bidulescu7 of Type 2 Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study https://doi.org/10.2337/dc20-0733 OBJECTIVE To examine the association between dietary intake of choline and betaine with the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS Among 13,440 Atherosclerosis Risk in Communities (ARIC) study participants, the prospective longitudinal association between dietary choline and betaine intake and the risk of type 2 diabetes was assessed using interval-censored Cox pro- portional hazards and logistic regression models adjusted for baseline potential confounding variables. 1Tennessee Clinical and Translational Science In- RESULTS stitute, University of Tennessee Health Science Among 13,440 participants (55% women, mean age 54 [SD 7.4] years), 1,396 Center, Memphis, TN CARDIOVASCULAR AND METABOLIC RISK 2 developed incident type 2 diabetes during median follow-up of 9 years from 1987 to Department of Preventive Medicine, University fi ofTennessee HealthScienceCenter,Memphis,TN 1998. There was no statistically signi cant association between every 1-SD increase 3Department of Epidemiology, College of Public in dietary choline and risk of type 2 diabetes (hazard ratio [HR] 1.01 [95% CI 0.87, Health, University of Kentucky, Lexington, KY 1.16]) nor between dietary betaine intake and the risk of type 2 diabetes (HR 1.01 4Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC [0.94, 1.10]). Those in the highest quartile of dietary choline intake did not have a 5 fi Department of Nutrition, University of North statistically signi cant higher risk of type 2 diabetes than those in the lowest choline Carolina at Chapel Hill, Chapel Hill, NC quartile (HR 1.09 [0.84, 1.42]); similarly, dietary betaine intake was not associated 6Nutrition Research Institute, University of North with the risk of type 2 diabetes comparing the highest quartile to the lowest (HR 1.06 Carolina at Chapel Hill, Kannapolis, NC 7 [0.87, 1.29]). Among women, there was a higher risk of type 2 diabetes, comparing Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana thehighest to lowest dietary choline quartile(HR 1.54[1.06, 2.25]),while inmen,the University, Bloomington, IN fi association was null (HR 0.82 [0.57, 1.17]). Nevertheless, there was a nonsigni cant Corresponding author: Aurelian Bidulescu, abidules interaction between high choline intake and sex on the risk of type 2 diabetes (P 5 @indiana.edu 0.07). The results from logistic regression were similar. Received 3 April 2020 and accepted 11 August 2020 CONCLUSIONS This article contains supplementary material online Overall and among male participants, dietary choline or betaine intakes were not at https://doi.org/10.2337/figshare.12814169. associated with the risk of type 2 diabetes. Among female participants, there was a © 2020 by the American Diabetes Association. trend for a modestly higher risk of type 2 diabetes among those with the highest as Readers may use this article as long as the work is compared with the lowest quartile of dietary choline intake. Our study should properly cited, the use is educational and not for profit, and the work is not altered. More infor- inform clinical trials on dietary choline and betaine supplementation in relationship mation is available at https://www.diabetesjournals with the risk of type 2 diabetes. .org/content/license. Diabetes Care Publish Ahead of Print, published online September 8, 2020 2 Dietary Choline and Betaine and Type 2 Diabetes Diabetes Care Type 2diabetes is a major health problem Atherosclerosis Risk in Communities 66-item version of the Willett semiquan- globally and in the U.S. (1,2). Dietary (ARIC) cohort. titative food frequency questionnaire habit is a leading contributor to morbid- (FFQ) (18). The dietary choline and be- ity and mortality globally (3) and is a most RESEARCH DESIGN AND METHODS taine intakes were estimated based on prominent risk factor for type 2 diabetes Study Population the daily serving sizes of the food items in addition to obesity, fat distribution, Data for the current study were obtained known to have choline and betaine by physical inactivity, age, and family history from the ARIC study cohort (13). The summing the amount of choline and ofdiabetes(4,5).Thereisstrongevidence baseline ARIC cohort examination was betaine in each food item per serving size for the association between food groups conducted from 1987 to 1989 and in- based on the U.S. Department of Agri- and the risk of type 2 diabetes, but there cluded 15,792 men and women fromfour culture food content database (19,20). remains a huge gap in evidence on the U.S. communities including Forsyth County, potential association between specific NC; Jackson, MS; suburbs of Minneapolis, Primary Outcome dietary nutrients such as choline and MN; and Washington County, MD. Par- Incident type 2 diabetes was the primary betaine and the risk of type 2 diabetes. ticipants were followed up through an- outcome of interest in the study and was Given the involvement of choline (an nual telephone interviews and review of ascertained at visit 2 (1990–1992), visit essential nutrient) and betaine (main hospitalizations. Extensive examinations 3 (1993–1995), and visit 4 (1996–1998) methyl donor) in the one-carbon cycle were conducted initially every 3 years, among those free of type 2 diabetes at with possible epigenetic effects, there with the latest examination currently baseline. Participants with fasting blood $ is a growing interest in the association underway. Participants were aged 45–64 glucose level 126 mg/dL, taking diabe- between dietary choline and betaine years at baseline. Participants were ex- tes medication, or reporting a physician intake, both found in a variety of foods, cluded from this analysis if they had diagnosis of diabetes were considered to and the risk of diseases in humans. baseline type 2 diabetes (n 5 2,014), if have type 2 diabetes, while those with , However, there are only a few previous they had missing values for dietary cho- fasting blood glucose level 126 mg/dL human studies on dietary choline and line, dietary betaine, type 2 diabetes, or who were not taking diabetes medi- 5 betaine intake and the risk of type 2 other relevant covariates (n 127), or if cations were considered free of type 2 diabetes. diabetes with inconsistent results. A re- they were of a race other than black 5 5 cent study among men found a lower risk or white (n 48). Participants (n 163) of type 2 diabetes in those with the with improbable total calorie intake Covariates # . The covariates in the study collected at highest choline intake as compared with ( 500 kcal/day or 5,000 kcal/day) study baseline included sociodemographic those with the lowest choline intake (6). were also excluded from the analysis 5 variables (age, sex, race, and education); Extant literature points to an association (14). All participants (n 13,440) with complete data on exposure variables, BMI; health behaviors (smoking and alco- between dietary consumption of phos- covariates, and outcome variables were hol use); total cholesterol; and intake of phatidylcholine (7) as well as plasma, included in the final analysis. Insulin total calories, folate, magnesium, vitamin serum, or urine metabolites of choline resistance, an impaired response of pe- B6, vitamin B12, methionine, and animal and risk of type 2 diabetes (8). Trimethyl- ripheral tissues to insulin action, was fat. amine-N-oxide (TMAO), a microbiota- defined based on the HOMA of insulin dependent metabolite of dietary choline, is resistance, which was calculated using: Statistical Analysis found to be directly associated with the (FPI 3 FPG)/22.5, in which FPI is fasting Baseline participant characteristics across risk of type 2 diabetes (9). At the same plasma insulin concentration (milliunits the choline quartiles were compared time, some studies suggest that dietary per liter) and FPG is fasting plasma using ANOVA for normally distributed choline and betaine intakes are associ- glucose (millimoles per liter) (15). An and Kruskal-Wallis tests for nonnormally ated with better insulin sensitivity in HOMA of insulin resistance cutoff value distributed continuous variables and x2 humans (10). The enzymes in the one- of $4.70 (80th percentile) was used to test for categorical variables. Interval- carbon cycle that involves choline and define insulin resistance (16). Impaired censored Cox proportional hazards re- betaine are differently expressed in glucose tolerance was defined based on gression models sequentially adjusted males and females and result in higher fasting blood glucose. Participants with for baseline covariates were fit to de- choline and betaine metabolites in fe- fasting blood glucose of 100–125 mg/dL termine the longitudinal association be- males than males (11). There are also were classified as meeting the definition tween dietary choline and betaine intake differences in choline requirements (12). of impaired fasting glucose (17). In a with the risk of type 2 diabetes consid- Given that dietary habits are modifi- sensitivity analysis, we excluded partic- ering cubic splines of baseline hazard. able, examination of the association of ipants with impaired glucose tolerance Covariates adjusted for in model 1 were dietary choline intake with the risk of and insulin resistance conditions with an age, race, sex, BMI, alcohol intake, and type 2 diabetes may inform dietary mod- underlying abnormality of glucose me- smoking, and the exposure variables ifications, which may help reduce the risk tabolism and considered precursors of (choline and betaine) were mutually attributable to choline. In this study, we diabetes. adjusted.
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