1. A Low-Fat Dietary Pattern Slows Progression of Diabetes: Results from the WHI Dietary Modification Trial
Barbara V Howard, PhD
Sr Scientist , MedStar Health Res. Inst.
Professor Of Medicine, GU School of Medicine

2. Definition of Diabetes
At enrollment prevalent diabetes was defined as a positive response to the question “ Did a doctor ever say that you had sugar diabetes or high blood sugar when you were not pregnant?” During the semiannual follow-up contacts, documentation was limited to treated diabetes when participants were asked, “Since the date given on the front of this form, has a doctor prescribed any of the following pills or treatments?” Choices included “pills for diabetes” and “insulin shots for diabetes.”

3. Risk of Treated Diabetes in the WHI Dietary Modification Trial
N=3,341 cases
7.1% intervention
7.4% comparison
Tinker et al, Arch Intern Med. 2008;168(14):

4. Conclusions at end of Intervention
A low-fat diet alone did not result in a decreased risk of developing treated diabetes mellitus among generally healthy postmenopausal women.
In subgroup analyses, women reporting the greatest decreases in total fat intake showed a decreased risk of diabetes. However, the decreased risk may have been related to the ad libitum low-fat diet and consequent weight loss experienced among participants in the intervention group.

5. Participants 48,835 women entered the DMI trial
8.1 years avg FU
34,674 participated in FU thru 2015 (71%)
Median 17.3 years
Analysis was done on 47,023 women- those taking insulin at baseline were excluded
Serum glucose and insulin were measured in 2324 women at baseline and in yrs 1,3, and 6 (5.8%)

6. Aim
Explore the impact of the DMI on progression of diabetes as indicated by use of oral agents and insulin

7. Baseline characteristics of dietary trial participants stratified by baseline diabetes status

8. Baseline characteristics of dietary trial participants stratified by baseline diabetes status (cont’d)

9. Diabetes outcomes during the intervention period among participants that did not report treated diabetes at baseline (n=45579)

10. Diabetes outcomes during the intervention phase among participants that reported taking pills at baseline (n=1444)

11. Diabetes Outcomes in the Dietary Modification Trial by study period

12. Measures of Fasting Glucose in the Dietary Modification Trial by study period
Glucose levels in intervention vs comparison were 94.9 vs 96.3 mg/dl (2% lower)
ALL RESULTS SIGNIFICANT AFTER ADJUSTMENT FOR WEIGHT SSND WEIGHT CHANGE

13. Subgroup analysis: Time from randomization to first report of insulin during the intervention period (T2)

14. Subgroup analysis: Time from randomization to first report of insulin (T2; cont’d)

15. Summary and Conclusions
Rate of initiation of insulin was lower in intervention group without DM at baseline
Effect greatest in those with MS or central obesity
Progression from NGT to abnormal glucose tolerance reduced 25% in intervention group and avg glucose was lower
The intervention appears to slow the progression of diabetes

16. Co-authors Aaron Aragaki, MS Lesley Tinker, PhD
Matthew Allison, MD, MPH
Melanie Hingle, PhD, MPH, RD
Karen Johnson, MD,MPH
JoAnn Manson, MD, DrPH
Aladdin Shadyab, PhD
James Skikaney, PhD
Linda Snetselaar, PhD, RD
Cynthia Thomson, PhD, RDN
Oleg Zaslavsky, PhD
Ross Prentice, PhD

17. Backup

18. Subgroup analysis: Time from pills to first report of insulin during the intervention period among women that initiated pills during follow−up (T3)

19. Women’s Health Initiative
48,835
36,282
3 Controlled Trials
27,347
Hormone Therapy Trials
Calcium/Vitamin D Trial
Dietary Modification Trial:
Breast & Colorectal Cancers (Coronary Heart Disease 2 endpoint)
Overlapping participation in the clinical trials offers a cost-efficient design.
Women invited to participate in HRT and DM after meeting eligibility criteria and providing informed consent.
93,676
1 Observational Study
Observational Study
161,808 women total

20. Rationale for Design of the Intervention
Primary goal was to test the theory that reducing total fat intake to 20% of calories would decrease the risk of breast cancer and colorectal cancer (cancer was primary outcome: both saturated and polyunsaturated fats had been implicated)
Achieving 20% calories from fat required reducing fat across the board, rather than targeting only saturated and trans fat and allowing replacement with other fats
CHD was secondary outcome: expectation that restricting fat to 20% calories would reduce saturated and trans fats sufficiently to impact risk of CHD

21. Study Design
Target sample size 48, % Intervention; 60% Comparison
Excludes women with prior breast or colorectal cancer and with low fat intake (<32%)
Age and ethnicity goals
Projected power
Invasive breast cancer 86%
Colorectal cancer 90%
Coronary heart disease 86%
Dietary intervention program based on NCI- sponsored feasibility studies

22. WHI DM Trial 373,092 completed the eligibility screening form
316,953 excluded (refused, low fat intake, info not avail)
WHI DM Trial
56,139
eligible
7,304 excluded (staff/participant reevaluation, history of breast cancer, other)
48,835 randomized
Intervention
19,541
Comparison 29,294
Status 3/31/05
17,674 alive & retained
1,867 lost, deceased, or withdrew
Status 3/31/05
26,677 alive & retained
2,667 lost, deceased, or withdrew
19,541 included in analysis
29,294 included in analysis
Dietary

23. Dietary Change Goals: Intervention Group
20% energy from fat
5 or more fruit and vegetable servings daily
6 or more grain servings daily
Photos courtesy of USDA Agricultural Research Service

24. Structure of the intervention- Decrease Fat Intake, Increase Vegetables, Fruits and Grains
18 group sessions Year 1
Quarterly maintenance sessions Year 2 and beyond
CORE
Baseline
End of DM Trial
Motivational Interviewing –3 personal contacts
Targeted Messaging – Mailing
Tailored Feedback: Personal Evaluation of Fat Intake – Group sessions
AUGMENTATIONS
Tailored Feedback: Personal Evaluation of Fat Intake – Mailing
Clinical Center augmentations
Mean Follow-up 8.1 yrs

25. WHI DM Trial Achievement Percent energy from fat
Prentice RL et al. Women's Health Initiative Trial of a Low-fat Eating Pattern and Breast Cancer

26. Dietary Changes in the Intervention Group: Types of Fat
Howard BV et al. JAMA Feb 2006

27. Dietary Intake Intervention vs Control: Fruits, Vegetables, and Grains
Fruits and Vegetables
Grains
Howard BV et al. JAMA Feb 2006

28. Trend Analyses-Greater Effects in :
those in the intervention who reached the lowest levels of
saturated fat (HR 0.81 in the group that consumed < 6.1%, p < 0.001, adjusted HR = 0.82, p = 0.05) and
trans fat (HR 0.81 in group consuming < 1.1%, p < .001, adjusted HR = 0.84, p = 0.10)
or the highest levels of
vegetables/fruits (HR = 0.88 in the group that consumed > 6.5 servings/day, p < .001, adjusted HR = .89, p = .11).

29. Change in Body Weight by Randomization Group