Data Collection

1.2.1 RECRUITMENT AND FOLLOW-UP

Of 500 000 women initially invited and mailed a questionnaire to participate in the study, about 100 000 agreed to participate¹⁶⁶. With respect to age and region of residence, the respondents and the non-respondents presented similar characteristics. Since then, self-administered questionnaires (Q1-Q11) have been sent to participants every 2-3 years (Figure 22) and the average participation rate has remained high (83% for the 11 questionnaire cycles) and the loss to follow-up since 1990 has remained low (3%; women who either: never answered a questionnaire, withdrew from the study, or whose contact information was lost).

1.2.2 OVERVIEW OF DATA COLLECTED

The questionnaires collected anthropometric, lifestyle, and health status data and allowed for the update of longitudinal data by repeating identical questions to update information on health status and factors such as menopause, smoking, or weight throughout follow-up.

A biological bank was also created from blood samples collected between 1994 and 1999 from approximately 25 000 participants (participation rate ~40%). Between 2009 and 2011, about 44 775 saliva samples were further collected from women who hadn’t given blood samples (participation rate ~69%).

In addition, data are available from the MGEN, which updates the vital status and address of participants every 3 months, and since January 1^st, 2004, has also provided data on drug reimbursements.

FIGURE 22. CALENDAR OF SELF-ADMINISTERED QUESTIONNAIRES IN THE E3N COHORT STUDY

1.2.3 THE DIETARY QUESTIONNAIRE

Dietary data was collected twice in E3N, once in 1993 and again in 2005, using a validated 208-item food frequency questionnaire¹⁷⁰. The first food frequency questionnaire (FFQ) was sent to 93 055 women and had a response rate of 80% and the second was sent to 93 121 women and had a response rate of 77%. The FFQ was designed to assess the habitual diet of the previous year. It took food and drink consumption throughout the day into account, keeping in mind French meal patterns, and included questions regarding each meal occasion, as well as snacks and appetizers.

The questionnaire was divided into two parts: a quantitative and a qualitative section. The quantitative section described the habitual frequency and portion sizes consumed, based on 66 food types and items grouped by 8 meal occasions (breakfast, morning snack, appetizer before lunch, lunch, afternoon snack, appetizer before dinner, dinner, after-dinner snack) (Figure 23). To quantify the frequency of consumption, 11 frequency categories were used: never or less than once per month, 1, 2, or 3 times per month, or 1-7 times per week and the quantity consumed was estimated using standard units (such as number of eggs, tablespoons), or portion sizes that were indicated with the aid of a photo booklet.

FIGURE 23. EXTRACT FROM THE QUANTITATIVE SECTION OF THE FFQ USED IN E3N

The second section allowed a more detailed description of each food consumed from each of the 6 food groups (cooked vegetables, salads, fruit, meat, fish, and dairy) and the frequency of its consumption (never, 1-3 times/month or 1-7 times/week). Detailed data were also obtained on the method of cooking, fats and sugar used. This section allowed the data from the first section to be weighed by that from the second and to calculate the average daily consumption of 208 types of foods and drinks.

1.2.4 FATTY ACID INTAKE

FA consumption was estimated using the database of food nutritional composition published by ANSES (the French Agency for Food, Environmental, and Occupational Health & Safety) and the results from the FFQ. For each woman, intakes of the following principal FA groups were obtained: total saturated fatty acids (SFAs), total monounsaturated fatty acids (MUFAs), total polyunsaturated fatty acids (PUFAs), (including total omega-3 polyunsaturated fatty acids (n-3 PUFAs) and total omega-6 polyunsaturated fatty acids (n-6 PUFAs)), and total trans unsaturated fatty acids (TFAs), in g/day. In addition, the consumptions of individual n-6 PUFAs: linoleic acid (LA; 18:2n6) and arachidonic acid (AA; 20:4n6), and individual n-3 PUFAs: α-linolenic acid (ALA; 18:3n3), eicosapentaenoic acid (EPA; 20:5n3), docosapentaenoic acid (DPA; 22:5n3), and docosahexaenoic acid (DHA; 22:6n3) were also estimated. However, only the FA intakes at Q3 were available for analyses.

1.2.5 ASSESSMENT OF TYPE 2 DIABETES

Cases of T2D were first identified either in follow-up questionnaires (with declaration of at least one of the following: (1) T2D, (2) a self-reported, physician-recommended diabetic diet, (3) use of diabetic medication, or (4) hospitalization due to diabetes) or they were identified as receiving diabetic drug reimbursements from health insurance records at least once between January 2004 and March

2012¹⁷¹. Those who were identified in both manners were considered validated. In 2012, all women (n=7649) were mailed a diabetes-specific questionnaire which included questions on the circumstances of the diagnosis (year, symptoms, biological exams, etc.), management (diabetic diet, physical activity, medications), and results of their most recent concentrations of fasting glucose and HbA1c. Cases were validated if one of the following was met: (1) fasting plasma glucose

≥7.0 mmol/L, (2) random glucose ≥11.1 mmol/L at diagnosis, (3) report of diabetic medication use, or (4) last values of fasting glucose or HbA1c concentrations ≥7.0 mmol/L or ≥7%, respectively.

Consequently, 5238 cases of T2D could be validated in E3N.

In 2014, women with validated cases of T2D were invited to answer the AfterDiab questionnaire, which inquired about their diabetes (diagnosis, results from their last exams), treatment, diabetes-related complications (heart, digestive system, kidneys, eyes, feet, and teeth) and their quality of life (sleep, state of health, living with diabetes). A total of 3473 women responded to this questionnaire and were then included in the E3N-AfterDiab study, which is also part of the EPIC sub-study devoted to diabetes: Interaction of genetic and lifestyle factors on the incidence of type 2 diabetes (InterAct).

1.2.6 ASSESSMENT OF RETINOPATHY

As diabetic macular edema (DME) is considered a further complication of DR¹, potential cases of DR were first identified in the AfterDiab questionnaire with the declaration of “yes” to at least one of the following: (1) retinopathy, (2) DME, (3) the loss of vision in at least one eye, or (4) laser treatment. Validation questionnaires were then mailed to the potential cases (n=889), inquiring about a diagnosis of DR,

DME, or laser treatment and requesting a copy of the most recent ophthalmological assessment.

659 validation questionnaires were returned, for a response rate of 74.1%. Cases of DR were considered validated if one of the following was met: “yes” response to retinopathy in both questionnaires and/or confirmation through ophthalmological assessment records and/or “yes” to retinopathy in the validation questionnaire and/or declaration of DR in AfterDiab and declaration of either laser treatment or DR eye injections in the validation questionnaire. Otherwise, respondents, non-respondents and the rest of the AfterDiab population were classified as non-cases. Cases of DME were validated in the same manner. In total, 77 cases were identified, containing 60 cases of DR and 35 cases of DME.