1. Prospective Association of Sweet Beverage Intake with Incident Type 2 Diabetes: The EPIC-Norfolk Study Laura O’Connor MRC Epidemiology Unit 25 th June 2014, Institute of Public Health Away Day, 2014

2. Type 2 diabetes

3. Background – sweet beverages & T2D Sugar sweetened beverages (SSB) positive association Meta-analysis of 8 studies (cases=15043) EPIC-InterAct study (cases=11,684) Other sugar sweetened beverages ? Artificially-sweetened beverage (ASB) null & positive associations – role of confounding & reverse causality by adiposity not clear Fruit juice (100%) null & positive associations – limited evidence RR 1.18 (1.06,1.32) per serving (12 oz) RR 1.25 (1.10,1.42) per serving (12 oz)

4. Background – sweet beverages & T2D Sugar sweetened beverages (SSB) positive association Meta-analysis of 8 studies (cases=15043) EPIC-InterAct study (cases=11,684) Other sugar sweetened beverages ? Artificially-sweetened beverage (ASB) null & positive associations – role of confounding & reverse causality by adiposity not clear Fruit juice (100%) null & positive associations – limited evidence

5. Background – sweet beverages & T2D Sugar sweetened beverages (SSB) positive association Meta-analysis of 8 studies (cases=15043) EPIC-InterAct study (cases=11,684) Other sugar sweetened beverages ? Artificially-sweetened beverages (ASB) null & positive associations – role of confounding & reverse causality by adiposity not clear Fruit juice (100%) null & positive associations – limited evidence

6. Background – sweet beverages & T2D Sugar sweetened beverages (SSB) positive association Meta-analysis of 8 studies (cases=15043) EPIC-InterAct study (cases=11,684) Other sugar sweetened beverages ? Artificially-sweetened beverages (ASB) null & positive associations – role of confounding & reverse causality by adiposity not clear Fruit juice (100%) null & positive associations – limited evidence Reducing SSB consumption is recommended Insufficient evidence for appropriate alternatives to lower risk of diabetes

7. Aim 1.Associations of sweet beverage intake with T2D: 2.How substituting alternative beverages for sweet beverages affect the incidence of T2D SSBSoft drinks Sweetened tea & coffee Sweetened milk beverages ASB Fruit juice (100%)

8. Methods Study design & participants EPIC Norfolk Study 25639 UK adults aged 40-79 at baseline Outcome – incident T2D Incident cases ascertained until 31 st July 2006 Medical record linkage 847 cases 10.8 years of follow-up

9. Per standard serving 4 intake categories: non-consumers & consumers split by tertile Methods – Exposure: sweet beverage intake Detailed prospective 7-day food diary 336 g/d 150 g/d 280 g/d

10. Methods – Statistical analysis Cox proportional hazards regression for each sweet beverage type: per serving and by intake category Substitution non-sugar sweetened beverages for sweet beverages per serving

11. Results – baseline characteristics Soft drinks broadly similar to total cohort Sweetened tea & coffee lower social class “less healthy” diets Sweetened milk beverages lower social class “less healthy” diets ASB younger, more women, more obese more physically active, lower EI Fruit juice (100%) higher social class “healthier diets”

12. Results Prospective association of sweet beverage intake & T2D, HR (95%CI) per serving Non- consumers High consumers Tertile 3 Soft drinks336 g/dRange: 142-3314 g/d Adjusted model 1.21 (1.05, 1.39)1.25 (1.05, 1.50) + BMI and waist circumference1.14 (1.01, 1.32)1.18 (0.98, 1.41) Sweetened tea & coffee280 g/dRange: 877-5096 g/d Adjusted model 0.98 (0.94, 1.02)0.95 (0.77, 1.16) + BMI and waist circumference1.03 (0.99, 1.07)1.22 (0.99, 1.50) Sweetened milk beverages280 g/dReferenceRange: 211-2653 g/d Adjusted model 1.22 (1.05, 1.43)group1.41 (1.16, 1.73) + BMI and waist circumference1.27 (1.09, 1.48)1.49 (1.22, 1.81) ASB336 g/dRange: 169-5848 g/d Adjusted model 1.22 (1.11, 1.33)1.65 (1.31, 2.07) + BMI and waist circumference1.06 (0.93, 1.20)1.18 (0.94, 1.50) Fruit juice150 g/dRange: 123-1372 g/d Adjusted model 1.01 (0.88, 1.15)0.92 (0.75, 1.13) + BMI and waist circumference1.04 (0.92, 1.19)0.98 (0.80, 1.21) Adjusted for age, sex, social class, education level, family history of diabetes, physical activity level, smoking status, alcohol consumption, season, mutual adjustment for intake of other sweet beverages, total energy intake

13. Results Prospective association of sweet beverage intake & T2D, HR (95%CI) per serving Non- consumers High consumers Tertile 3 Soft drinks336 g/dRange: 142-3314 g/d Adjusted model 1.21 (1.05, 1.39)1.25 (1.05, 1.50) + BMI and waist circumference1.14 (1.01, 1.32)1.18 (0.98, 1.41) Sweetened tea & coffee280 g/dRange: 877-5096 g/d Adjusted model 0.98 (0.94, 1.02)0.95 (0.77, 1.16) + BMI and waist circumference1.03 (0.99, 1.07)1.22 (0.99, 1.50) Sweetened milk beverages280 g/dReferenceRange: 211-2653 g/d Adjusted model 1.22 (1.05, 1.43)group1.41 (1.16, 1.73) + BMI and waist circumference1.27 (1.09, 1.48)1.49 (1.22, 1.81) ASB336 g/dRange: 169-5848 g/d Adjusted model 1.22 (1.11, 1.33)1.65 (1.31, 2.07) + BMI and waist circumference1.06 (0.93, 1.20)1.18 (0.94, 1.50) Fruit juice150 g/dRange: 123-1372 g/d Adjusted model 1.01 (0.88, 1.15)0.92 (0.75, 1.13) + BMI and waist circumference1.04 (0.92, 1.19)0.98 (0.80, 1.21) Adjusted for age, sex, social class, education level, family history of diabetes, physical activity level, smoking status, alcohol consumption, season, mutual adjustment for intake of other sweet beverages, total energy intake

14. Results – Substitution, non-sugar sweetened beverage in place of a sweet beverage HR (95%CI) Most adjusted model including BMI and waist circumference

15. Results – Substitution, non-sugar sweetened beverage in place of a sweet beverage HR (95%CI) Most adjusted model including BMI and waist circumference

16. Results – Substitution, non-sugar sweetened beverage in place of a sweet beverage HR (95%CI) Most adjusted model including BMI and waist circumference

17. Results – Substitution, non-sugar sweetened beverage in place of a sweet beverage HR (95%CI) Most adjusted model including BMI and waist circumference

18. Results – Substitution, non-sugar sweetened beverage in place of a sweet beverage HR (95%CI) Most adjusted model including BMI and waist circumference

19. Results – Substitution, non-sugar sweetened beverage in place of a sweet beverage HR (95%CI) Most adjusted model including BMI and waist circumference

20. Summary Soft drinks and sweetened milk beverage intake was associated with higher T2D risk, independent of adiposity Sweetened tea/coffee, ASB and fruit juice was not associated Consuming ASB in place of soft drinks and sweetened milk was not associated with T2D Consuming drinking water or unsweetened tea & coffee in place of any SSB was inversely associated with T2D

21. Population impact of sweet beverage intake on T2D % Population Attributable Fraction (PAF) of T2D incidence attributable to high % total energy from all sweet beverages Assuming causality 3 scenarios Contribution of sweet beverages PAF (95% CI) <10% total energy3 (1 to 7) % <5% total energy7 (1 to 13) % <2% total energy15 (3 to 25) %

22. Strengths and Limitations Strengths Prospective detailed food diary data examine individual beverage types inclusion of beverages not previously examined Incident T2D ascertained/verified using medical record linkage Limitations Did not account for change in sweet beverage intake Reporting bias Residual confounding

23. Conclusion Consumption of soft drinks and sweetened milk beverages was associated with higher T2D risk Promoting drinking water or unsweetened tea/coffee in place of SSB may help curb the escalating diabetes epidemic 3 to 15 % of incident diabetes cases might be prevented if consumers of sweet beverages reduced intakes to below a range of 10 and 2 %TE

24. Acknowledgements Prospective Associations of Sweet Beverage Intake with Incident Type 2 Diabetes and Effects of Substitutions with Non-Sugar Sweetened Alternatives: The European Prospective Investigation into Cancer and Nutrition Norfolk Study, UK Laura O’Connor, PhD; Fumiaki Imamura, MS, PhD; Marleen AH Lentjes, MSc; Kay-Tee Khaw, FMedSci; Nicholas J Wareham, PhD, FRCP; Nita G Forouhi, PhD FFPHM With thanks to: Amit Bhaniani & Robert Luben Funding: The EPIC Norfolk Study is supported by programme grants from the Medical Research Council UK and Cancer Research UK

25. Thank you

26. Sensitivity analyses Adjusting for plasma vitamin C as an objective marker of dietary quality fibre intake as a marker of dietary quality non-sweet beverage energy in place of total energy Excluding those with prevalent chronic disease (n=2332) those with self-reported hypertension or hypercholesterolaemia (n=4943) those with incomplete food diary records (<7 days) (n=2219) the top 1% of consumers for each sweet beverage separately and simultaneously Including those originally excluded for having missing covariate data (n=591) Adjusting for plasma vitamin C, strengthened the association of fruit juice from HR (95%CI): 1.04 (0.92, 1.18) to 1.22 (1.07, 1.41)

27. Potential Mechanisms SSB risk of T2D Via effects on adiposity liquid calories are not fully compensated for, promoting weight- gain Independently via glycaemic effects of consuming large amounts of rapidly absorbable sugars metabolic effects of fructose Tea/coffee decrease risk of T2D Tea catechins inhibit carbohydrate digestive enzymes Black & green tea increase insulin sensitivity Green tea prevents damage to pancreatic β cells Coffee? Antioxidant in vivo, chlorogenic acid may delay glucose absorption