More information on the E3N cohort study here: www.e3n.fr Background - It has been extensively shown, mainly in US populations, that sugar sweetened beverages (SSB) are associated with an increased risk for type 2 diabetes (T2D), but less is known on the effects of artificially sweetened beverages (ASB). Objective – To evaluate the association between self-reported SSB, ASB and 100% fruit juice consumption and T2D risk over 14 years of follow-up in the French prospective E3N-EPIC cohort. Design – A total of 66 118 women were followed from 1993 and 1 369 incident cases of T2D were diagnosed during the follow-up. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for T2D risk. Results – The average consumption of sweetened beverages, among consumers only, was 328 and 568 mL/week respectively for SSB and ASB. Women in the highest quartiles of SSB and ASB consumers were at increased risk of T2D with HRs of 1.34[1.05,1.71] and 2.21[1.56,3.14] for women consuming more than 359 and 603 mL/week of SSB and ASB respectively, compared to non-consumers. Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage (P=0.0088 and P<0.0001). In sensitivity analyses, the associations were partly mediated by BMI, although there was still a strong significant independent effect. No association was observed for 100% fruit juice consumption. Conclusions - Both SSB and ASB consumption were associated with an increased T2D risk. We cannot rule out that other factors than ASB consumption we did not control for are responsible for the association to diabetes, and randomized trials are required to prove a causal link between ASB consumption and type 2 diabetes.

1. Guy Fagherazzi, PhD
Inserm U1018 team 9
“Nutrition, Hormones and Women’s health”
Villejuif, FRANCE
Consumption of artificially and sugar
sweetened beverages and risk of type 2
diabetes in the E3N cohort

2. Article publié en janvier 2013
Consumption of artificially and sugar sweetened beverages and
incident type 2 diabetes in the E3N-EPIC cohort.

3. Diabetes
• More than 3 millions of diabetic in France, 347 millions globally
• 90% are diagnosed with type 2 diabetes
• Diabetes is a leading cause of blindness, amputation and kidney failure.
• Type 2 diabetes can be prevented

4. Sugar sweetened beverages (SSB)
• High consumption of SSB is associated with an increased
risk of:
– T2D,
– Weight gain,
– Obesity,
– Metabolic Syndrome,
– CHD,
– High blood pressure…
• Biological mechanisms
– No reduction of energy intake after consumption of SSB
– A rapid spike in blood glucose and insulin levels - insulin resistance
over time
What is known (1/2)

5. What is known (2/2)
Artificially sweetened beverages (ASB)
• Artificially sweetened beverages (ASB) and T2D
• Most of the studies failed to find an association, however a few
concluded to an increased risk of T2D
• No clear biological mechanisms
– Reverse causation?
– Preference for sweets and an appetite enhancer?
– Aspartame might induce a 30mn postprandial increase in insulin
levels equivalent to sucrose
Anton et al. 2012 Appetite

6. E3N-EPIC cohort
• E3N is the French part of the EPIC
cohort
• E3N: ”Etude Epidémiologique auprès de
femmes de l’Education Nationale”
• Prospective cohort 98,995 women aged
between 40 and 65 were recruited in
1990
• Main objective: To study risk factors of
women’s main chronic diseases (cancer,
diabetes, cardiovascular diseases...)
• Self-administered questionnaires sent
every 2 or 3 years
• 1993: diet-history questionnaire
– Sugar sweetened beverages
– Artificially sweetened beverages
– Pure-fruit juice

7. Diet-history questionnaire
• Asked in 1993: 238-item food-frequency questionnaire
– Adapted to the French meal pattern
– Validated against 24h-recall questionnaires
– Both a quantitative and a qualitative part
• Quantitative part: frequency & portion sizes per food group of food item
• Qualitative part: provide more information of items within one food group
7

8. Diet-history questionnaire
• Women were asked to report their food
consumption by meal
– Breakfast, Mid-morning snack, Appetizer,
Lunch, Afternoon snack, Appetizer,
Dinner, Night snack
• Women were helped with a photo
booklet to evaluate portion sizes
• Estimation of food consumption by
meal and by day + nutrients intakes
thanks to a food composition table
Meal Frequency Portion size
8

9. • Follow-up: 1993-2007
• N=66 118 women
• 1 369 incident validated diabetes cases
Baseline characteristics (in 1993)
– Age = 52.6 years
– 18.8% of women with BMI>25kg/m²
– Only 1 on 6 woman drink either ASB or SSB
– Mean SSB consumption = 328.3 ml/week
– Mean ASB consumption= 567.7 ml/week
– Mean 100% fruit juice consumption = 686.7 ml/week
Study population

10. Statistical analyses
• Cox models
– Age as the time scale
– Model 1 adjusted for
• years of education, smoking status
• physical activity
• hypertension, hypercholesterolemia
• use of hormone replacement therapy
• family history of diabetes
• alcohol intake, omega-3 fatty acid intake, carbohydrate intake, coffee, fruit and
vegetables, processed-meat consumption
• dietary pattern (Western or Mediterranean)
– Model 2 : model 1 + total energy intake
– Model 3 : model 2 + BMI (in kg/m²)

11. Influence of energy intake and BMI

12. Hazard ratios of T2D risk
Figure 1. Risk of type 2 diabetes according to categories of sugar and artificially sweetened
beverages and fruit juice consumptions. E3N cohort data (N=66 118).
0.5
1
1.5
2
2.5
SSB
ASB
FJ
P<0.01
P<0.0001 P=0.2823

13. Spline regression models
+59%

14. Sensitivity analyses
• Reverse causation?
– Exclusion of the 5 first years of follow-up
– Similar results were obtained for the ≠ types of beverages :
• Increased risk of T2D for high consumption of SSB and ASB, no
association for FJ
• Associations mediated by BMI or energy intake?
– Increased risks slightly attenuated but still strongly significant
when adjusting for energy intake or BMI
• Interaction with BMI?
– Strength of the associations was attenuated with increase in
BMI categories. No more associations in obese women
– Limited statistical power

15. Strengths and limitations
• First prospective study on a French population
• Validated diabetes cases
• Validated dietary questionnaire
• Low consumption of SSB and ASB, low variability
• No updated information on consumption during the
follow-up
• No information on the type of SSB, ASB or 100%
fruit juice
– But in 1993, the ASB market was mainly composed of
products made with aspartame

16. Take-home message
• Reverse causation is unlikely to explain completely the association for
ASB
• More studies are needed on the impact of ASB on chronic conditions
– The relationship might be not causal
– ASB consumption may be associated with a risky behavior for T2D.
• We should be more cautious regarding the promotion of ASB as an
healthy alternative.
Both ASB and SSB were found to be directly
associated with an increased risk of T2D,
independent of BMI, in a population of French
women

17. Acknowledgments
• Alice Vilier
• Françoise Clavel-Chapelon
• Beverley Balkau
Thanks for your attention!