Dietary modification puts the brakes on diabetes progression

From the WHI Clinical Coordinating Center, Public Health Sciences Division

The proportion of adults with diabetes in the U.S. has steadily climbed over the past several decades, and the prevalence of diagnosed diabetes is now at an all-time high. In addition, it is estimated that a third of all adults in the U.S. have prediabetes, an alarming statistic as this early impairment in blood glucose homeostasis is a major risk factor for the development of diabetes. With such a substantial proportion of the population diagnosed with or at a high risk for diabetes, identifying ways to reduce its burden is of great public health interest.

Past intervention trials revealed that weight loss achieved through lifestyle modification, including increased physical activity and a low-calorie, low-fat diet, is highly effective in reducing diabetes incidence. However, whether a low-fat dietary intervention alone, without a specific goal of weight loss, can also impact diabetes incidence has remained unknown. Drs. Ross Prentice and Lesley Tinker and Mr. Aaron Aragaki of the Public Health Sciences Division and collaborators addressed this gap by conducting secondary analyses of data collected from postmenopausal women in the Women’s Health Initiative (WHI) Clinical Trial. The results from this work were recently published in Diabetes Care.

The authors analyzed data collected during the large-scale WHI Dietary Modification Trial in which 48,835 women were randomized to either a non-weight loss, low-fat dietary pattern that increased fruit, vegetable, and grain intake or to a control group that did not modify their usual dietary pattern. Women in the dietary modification group reduced their fat intake by about 8% during the intervention phase. This intervention period lasted 8.1 years, and approximately 70% of the woman participated in a post-intervention follow-up, in which they were followed for a total cumulative period of 17.3 years.

To assess the effect of the dietary modification on diabetes, the authors employed a recently published composite outcome approach by Cespedes et al. that was “well suited to detect and characterize the nuanced influence that an intervention or risk factor may have on disease diagnosis and progression,” as described by Aragaki. The authors studied diabetes progression using this composite method by analyzing the transition from no diabetes to type 2 diabetes requiring antidiabetic pills and then the subsequent transition to the use of insulin as a composite outcome.

Diagram of hazard ratios of results.
Diabetes outcomes during the WHI dietary modification trial. Time from randomization to first report of insulin after pills (T2) is parsed into the component outcomes (T2 = T1 + T3): time from randomization to first report of pills for diabetes (T1) and time from pills to first report of insulin (T3). HR, hazard ratio; CI, confidence interval; p, significance level (p-value). Image provided by Mr. Aragaki

In women without diabetes at baseline, during the intervention period there was a trend towards reduced risk for the time to first use of diabetes requiring pills (see Figure, T1) and for the time from diabetes requiring pills to requiring insulin (see Figure, T3), although these did not reach statistical significance. However, when these outcomes were considered together (see Figure, T2) using the composite approach, it became clear that the dietary modification slowed diabetes progression, with a 26% reduction in the risk for diabetes requiring insulin. In the cumulative analysis of the intervention period plus the post-intervention follow-up, there was a significant 12% reduction in risk for diabetes requiring insulin.

Fasting blood glucose levels were also measured in a small cohort of the women. Separate analyses of this group revealed that the low-fat dietary pattern reduced the risk for the development of elevated fasting glucose (>100 mg/dL) by 25% during the intervention phase. This is a noteworthy finding because a fasting glucose level between 100 – 125 mg/dL is considered prediabetes.

Together, the results from this study suggest that a low-fat dietary pattern may slow the development and progression of type 2 diabetes. From a public health perspective, these findings are striking in that this modest lifestyle change may be highly feasible for many adults. “Our results support a hypothesis that a dietary intervention aimed at reducing fat intake and promoting greater intake of vegetables, fruits, and grains may have a long-term positive influence on slowing progression of type 2 diabetes,” said Aragaki.

When asked about the next steps, Aragaki indicated that the WHI dietary intervention participants “chose varying approaches towards reduction in total fat, so ongoing efforts will attempt to identify dietary pattern changes that enhance dietary benefits while avoiding any adverse effects.” Of the WHI low-fat dietary pattern, Aragaki noted additional recently published benefits in breast cancer mortality and the prevention of cardiovascular disease by Chelebowski et al., “women randomized to the dietary modification group were at 35% lower risk of death after breast cancer, and healthy normotensive women without prior history of cardiovascular disease were at 30% lower risk of coronary heart disease as reported by Prentice et al. It is hoped that ongoing efforts will provide actionable recommendations for healthy eating.” With the tremendous amount of lifestyle and dietary intake data collected from the WHI participants, there is no doubt that additional insight on the health effects of dietary modification will be gained from these follow-up analyses.

Howard BV, Aragaki AK, Tinker LF, Allison M, Hingle MD, Johnson KC, Manson JE, Shadyab AH, Shikany JM, Snetselaar LG, Thomson CA, Zaslavsky O, Prentice RL. 2017. A low-fat dietary pattern and diabetes: a secondary analysis from the Women's Health Initiative Dietary Modification Trial. Diabetes Care. doi: 10.2337/dc17-0534.

This research was supported by the National Institutes of Health.

Additional Citations:

Cespedes Feliciano EM, Prentice RL, Aragaki AK, Neuhouser ML, Banack HR, Kroenke CH, Ho GYF, Zaslavsky O, Strickler HD, Cheng T-YD, Chlebowski RT, Saquib N, Nassir R, Anderson G, Caan BJ.  2017. Methodological considerations for disentangling a risk factor's influence on disease incidence versus postdiagnosis survival: The example of obesity and breast and colorectal cancer mortality in the Women's Health Initiative. Int J Cancer. 141:2281-2290.

Chlebowski RT, Aragaki AK, Anderson GL, Thomson CA, Manson JE, Simon MS, Howard BV, Rohan TE, Snetselar L, Lane D, Barrington W, Vitolins MZ, Womack C, Qi L, Hou L, Thomas F, Prentice RL. 2017. Low-fat dietary pattern and breast cancer mortality in the Women’s Health Initiative randomized controlled trial. J Clin Oncol. 35:2919-2926.

Prentice RL, Aragaki AK, Van Horn L, Thomson CA, Beresford SA, Robinson J, Snetselaar L, Anderson GL, Manson JE, Allison MA, Rossouw JE, Howard BV. 2017. Low-fat dietary pattern and cardiovascular disease: results from the Women’s health Initiative randomized controlled trial. Am J Clin Nutr. 106:35-43.