1. Diet, Obesity, and Chronic Disease
The Kratz Lab at Fred Hutch
Mario Kratz, Ph.D.

2. ©2014 Fred Hutchinson Cancer Research Center

3. Focus of the Kratz Lab at Fred Hutch? ? ? ? ?
©2014 Fred Hutchinson Cancer Research Center

4. 1990 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

5. 1993 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14% %–19%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

6. 1996 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14% %–19%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

7. 1999 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14% %–19% ≥20%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

8. 2002 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14% %–19% %–24% ≥25%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

9. 2005 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14% %–19% %–24% %–29% ≥30%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

10. 2008 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14% %–19% %–24% %–29% ≥30%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

11. 2010 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2
No Data <10% %–14% %–19% %–24% %–29% ≥30%
Percentage of adults with BMI ≥ 30 kg/m2
©2014 Fred Hutchinson Cancer Research Center

12. Obesity & Chronic Disease?
©2014 Fred Hutchinson Cancer Research Center

13. Obesity & Chronic Disease
Risk of type 2 diabetes in relationship to obesity
Colditz et al.; Ann. Intern. Med. 1995; 122: 481-6
©2014 Fred Hutchinson Cancer Research Center

14. Obesity & Chronic Disease
Increase in risk of dying from specific types of cancer in obese men (BMI >35 kg/m2) compared to normal weight men.
Calle et al; N. Engl. J. Med. 2003; 348:
©2014 Fred Hutchinson Cancer Research Center

15. Obesity & Chronic Disease
Risk of cardiovascular disease in relationship to obesity & diabetes
10-year risk of developing cardiovascular disease
WOMEN
Normal weight
Obese
No diabetes
6.2%
9.3%
Diabetes
9.4%
10-year risk of developing cardiovascular disease
MEN
Normal weight
Obese
No diabetes
Diabetes
Fox et al.; Diabetes Care 2008; 31:
©2014 Fred Hutchinson Cancer Research Center

16. Obesity & Chronic Disease
Risk of cardiovascular disease in relationship to obesity & diabetes
10-year risk of developing cardiovascular disease
WOMEN
Normal weight
Obese
No diabetes
6.2%
9.3%
Diabetes
9.4%
41.9%
10-year risk of developing cardiovascular disease
MEN
Normal weight
Obese
No diabetes
Diabetes
Fox et al.; Diabetes Care 2008; 31:
©2014 Fred Hutchinson Cancer Research Center

17. Obesity & Chronic Disease
Risk of cardiovascular disease in relationship to obesity & diabetes
10-year risk of developing cardiovascular disease
WOMEN
Normal weight
Obese
No diabetes
6.2%
9.3%
Diabetes
9.4%
41.9%
10-year risk of developing cardiovascular disease
MEN
Normal weight
Obese
No diabetes
11.9%
22.8%
Diabetes
33.2%
47.6%
Fox et al.; Diabetes Care 2008; 31:
©2014 Fred Hutchinson Cancer Research Center

18. Obesity & Chronic Disease?
©2014 Fred Hutchinson Cancer Research Center

19. Obesity & Chronic Disease✔
But: How does being obese increase the risk for chronic disease?
©2014 Fred Hutchinson Cancer Research Center

20. Obesity & Chronic Disease
Dyslipidemia
Insulin Resistance
Chronic Disease
Obesity
Low-Grade Chronic Systemic Inflammation
Changes in Hormone Concentrations: Sex Steroid Hormones
Adiponectin Leptin
©2014 Fred Hutchinson Cancer Research Center

21. Obesity & Chronic Disease
Dyslipidemia
Insulin Resistance
Chronic Disease
Adipose Tissue Inflammation
Low-Grade Chronic Systemic Inflammation
Changes in Hormone Concentrations: Sex Steroid Hormones
Adiponectin Leptin
©2014 Fred Hutchinson Cancer Research Center

22. Introduction & Objective
DASI
DASI
DAIRY RCT
AIM
DAIRY RCT
CROSS- ROADS
©2014 Fred Hutchinson Cancer Research Center

23. Introduction & Objective
DASI
DASI
DAIRY RCT
AIM
DAIRY RCT
CROSS- ROADS
©2014 Fred Hutchinson Cancer Research Center

24. Anti-Inflammatory Milieu (AIM)-Diet Study
Based on a recent publication of our group (Kratz et al.; Cell Metab. 2014; 20: 1-12), we hypothesize that excessive diurnal exposure of adipose tissue to glucose, insulin, and fatty acids triggers ‘metabolic inflammation’.
Newly developed AIM diet minimizes adipose tissue exposure to glucose, insulin, and long-chain fatty acids.
Dietary intervention RCT to compare the effect of the AIM diet vs. USDA-diet on:
Adipose tissue inflammation
Insulin resistance
Glucose tolerance
©2014 Fred Hutchinson Cancer Research Center