The 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) score and diabetes risk in the Diabetes Prevention Program Outcomes Study (DPPOS) | BMC Nutrition

study population

The study protocol for DPP is publicly available at [20] and the design and methods for both DPP and DPPOS are detailed elsewhere (NCT00004992, NCT00038727). [16, 21,22,23]. Briefly, DPP was a multi-center, randomized, controlled clinical trial that recruited 3,234 participants (68% female, 45% from various ethnic/racial minority groups) from 27 clinical centers in the US (1996-1999). Eligible participants were ≥25 years old and had a body mass index (BMI) ≥24 kg/m2 (≥22kg/m2 for Asian/Pacific Islanders) and had a plasma glucose concentration between 5.3-6.9 mmol/L (95-125 mg/dL) in the fasting state and 7.8-11.0 mmol/L (140-199 mg/dL ) two hours after a 75 g oral glucose tolerance test (OGTT). Participants were excluded from this secondary analysis if they lacked dietary data (n=74), waist circumference (WC) or PA (n=4) or had energy outliers (n=9) at the beginning. Outliers were defined as values ​​that are more than two interquartile ranges above the 75th or below the 25th percentile on the logarithmic scale. The rate of missing data was low (~70% had diet and visitation data by age 15) and did not differ between treatment groups; missing data were randomly assumed to be missing. The final analytical cohort included 3,147 participants (see Supplementary Figure 1). Participants with no available nutritional data for Year 1 were excluded from analyzes assessing change in score from baseline to Year 1 (N=247).

DPP and DPPOS study designs

Participants in DPP were randomly assigned to receive intensive lifestyle intervention (ILS), metformin (MET), or a placebo pill (PLB). ILS participants were offered a 16-hour personalized curriculum over 24 weeks, followed by monthly sessions through DPP. The curriculum focused on diet, exercise, and behavior modification toward a low-fat, low-calorie diet (<25% kcal from fat) and ≥150 min/week of physical activity, with the primary goal of achieving ≥7% weight loss from baseline [17]. MET participants were instructed to take blinded metformin 850 g twice daily; PLB participants were matched with a placebo pill twice daily. Both the MET and PLB groups received standard written lifestyle recommendations and an in-person lifestyle session annually [22]. Participants were followed for an average of 3.2 years.

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Given the effectiveness of ILS, DPP was discontinued and participant groups were disclosed in July 2001; All participants were then offered the 16-session ILS curriculum [17] in a group format through a Healthy Lifestyle Program (HELP) during a 6-month bridge period [24] and invited to participate in the long-term follow-up study (DPPOS). Group Lifestyle HELP sessions were offered to DPPOS participants every three months to reinforce weight and activity goals. ILS participants were also offered 2-4 Booster Lifestyle Sessions twice a year. Metformin continued unmasked in the MET group. Years of follow-up are denoted as: years 0 (DPP baseline), 1 (DPP 1-year follow-up), and years 5, 6, 9, and 15 (DPPOS years 1, 2, 5, and 11) . The protocols were approved by the local institutional review boards of the participating study centers (Supplementary Table 1); all participants gave written informed consent.

Exposure: The 2018 WCRF/AICR score

The 2018 WCRF/AICR Score is used to assess compliance with the 2018 WCRF/AICR Cancer Prevention Recommendations [6]. Eight recommendations operationalized within the standardized rating system (Supplementary Table 2) relate to body weight, PA, fruits/vegetables and dietary fiber, ultra-processed foods, red and processed meats, SSBs and alcohol; the optional breastfeeding component was not included. Thus, overall scores ranged from 0 to 7 points, with a higher score indicating stronger agreement with the recommendations.

data collection

body composition

The body weight component of the score is calculated based on BMI (kg/m²).2) and toilet. BMI was estimated based on the height (cm) and weight (kg) of the participants. Height was reached at years 0, 1, and 15; the last measured height was used to calculate the BMI at each visit. Weight was measured twice a year and WC (cm) was measured annually by trained personnel in duplicate. If there was a deviation of more than 0.5 cm for height and toilet or 0.2 kg for weight, a third measurement was taken and the average of the three was given.

physical activity

PA was assessed at each annual visit for 15 years using the Modifiable Activity Questionnaire (MAQ), a valid and reliable tool for assessing moderate and severe PA (MVPA) in adults. [25, 26]. The 37 activities included in the questionnaire were considered MVPAs based on the guidelines of the 2011 Compendium of Physical Activities. As shown in Supplementary Table 2, participants were considered to meet the PA recommendation if they performed ≥ 150 min/week of MVPA (equivalent to 7.5 MET-hours/week).

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Study participants completed a modified version of the Insulin Resistance Atherosclerosis Study (IRAS) Feeding Frequency Questionnaire (FFQ) in person with trained staff [27]. The 117-item questionnaire recorded food reminders over the past year and was administered at years 0, 1, 5, 6, 9, and 15. Nutrient and energy estimates were obtained using the DietSys Nutrient Analysis Program and Nutrition Data System (Version 2.6 8A/23, Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN, USA) [27]. The data was used to calculate the five dietary components of the score (fruits/vegetables and fiber, fast foods, red and processed meats, SSBs and alcohol) and energy. Details of how each component was estimated are included in Supplementary Table 2.

Demographic covariates

Self-reported age (years), gender (male/female), race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, Native American, Asian/Pacific Islander), education (years), smoking (never, current, former ), family history for type 2 diabetes (yes/no), marital status (never married, living together, married, separated, divorced, widowed), and hormone therapy (for women, yes/no) were assessed at year 0.


Fasting glucose and HbA1c were measured every six months and OGTTs were performed annually. The primary endpoint was development of diabetes based on the 1997 American Diabetes Association criteria: fasting plasma glucose ≥ 7 mmol/L (≥ 126 mg/dL) or 2-hour plasma glucose ≥ 11.1 mmol/L (≥ 200 mg/dl) after an oral glucose load of 75 g [21], confirmed by repeat testing within six weeks. Participants’ results were collected for DPP up to July 31, 2001 and used for DPPOS up to January 2, 2014.

Statistical analysis

Descriptive statistics were used to examine characteristics of the study population. Comparisons between groups were calculated using ANOVA for continuous variables and chi-square tests for categorical variables. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association of the 2018 WCRF/AICR score with diabetes incidents over time, using person-years as the underlying time metric. The score was modeled as a continuous variable (ie risk per 1 point increase). To examine whether and how scores have changed over time (i.e., considering a time-dependent score) and how they relate to risk differences by group, the association between score changes from years 0–1 and the risk of diabetes by DPP (mean 3 years follow-up) and by DPPOS (~15 years follow-up). In addition, the relationship between time-dependent score changes over 15 years and diabetes risk was examined. Treatment group, age, gender, race/ethnicity, and smoking were tested as potential effect modifiers; Models were stratified as needed. Baseline models adjusted for age, gender, and baseline risk score. Multivariate models additionally adjusted for race/ethnicity, marital status, family history of type 2 diabetes, education, hormonal therapy, and baseline energy intake.

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Given the distribution of the fruit/vegetable and SSB data, sensitivity analyzes were performed, excluding participants with data outliers identified using the same approach described above, to determine if they significantly affected the estimates. Asian participants’ weight component cutoffs were adjusted in a second sensitivity analysis according to World Health Organization (WHO) guidelines and WCRF/AICR recommendations [6, 28]. In addition, a sensitivity analysis was performed to examine whether the results differed depending on the participation in DPPOS lifestyle sessions.

Finally, models were run to examine the independent associations of each individual WCRF/AICR score component. To further investigate the effect of weight change and physical activity, models were run to assess associations with body weight and the combined physical activity components; the five nutritional components combined; and the score without the weight component. All exploratory models were adjusted for the other components in the score and the covariates mentioned above. SAS version 9.4 (SAS Institute, Inc., Cary, NC) was used for all analyses. Statistical tests were two-sided with a significance level of 0.05.

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