Secondary analysis evaluates effect of Women’s Health Initiative dietary intervention.
A lower-fat diet, in addition to increased physical activity, has been shown to lower diabetes incidence in individuals with impaired glucose tolerance. The Women’s Health Initiative (WHI) Dietary Modification Trial (DMT) is the only large (n = 48,835), long-term, randomized low-fat, non–weight-loss diet trial. It was designed to study the effect of decreased fat intake (20% of calories) and increased vegetable/fruit (five servings per day) and grain (six servings per day) consumption on incidence of breast and colorectal cancers. Cardiovascular disease was a secondary end point, and data on diabetes were collected by self-report.
After the 8.1-year trial, a nonsignificant reduction in diabetes incidence was observed in intervention versus comparison group women. In the earlier analysis, however, the outcome was broadly defined as the time from randomization to first reported use of a glucose-lowering oral agent or injected insulin and did not explore the intervention’s impact on individual components of diabetes treatment as indicators of disease progression. For the current analysis, they separately investigated types of treatment and also had access to longitudinal summaries of glucose and medication histories at baseline and three other time points.
The objectives of this secondary analysis were to evaluate the effect of the WHI DMT intervention on specific diabetes-related outcomes during the intervention (8.1 years) and to assess the longer-term effects of the intervention on these outcomes during the post-intervention follow-up (median [SD] 9.8 [1.5] years), for a cumulative follow-up of 17.3 years.
Among women without baseline diabetes participating in a dietary and behavioral modification aimed at consuming a low-fat diet with increased vegetables, fruits, and grains, they observed a decreased risk for initiating insulin therapy during 8.1 years of intervention. The effect was greatest in those with central obesity or higher metabolic syndrome score at baseline. Blood glucose data in a 5.8% subsample of women with measured values were consistent with these findings, with reduction in glucose among intervention-group women without diabetes at baseline and a 25% reduction in rate of conversion from normal glucose tolerance to impaired fasting glucose in intervention-group women during the trial. Overall, given multiple testing considerations, the results from this secondary analysis show that a low-fat diet does not increase diabetes risk and suggest that the dietary intervention improved glycemia and slowed diabetes progression.
Notably, the women with baseline diabetes did not show significant improvements, but the medication data showed that women with baseline diabetes randomized to the intervention group decreased their use of diabetes medications compared with women with baseline diabetes randomized to the comparison group.
The WHI dietary intervention was multifaceted, resulting in changes in intake of most fatty acids and increased vegetable, fruit, and fiber intake. The observed results may be due to any or some combination of these changes. The major changes, however, were a reduction by ∼8% of total calories in fat intake and a corresponding increase by ∼8% of calories in carbohydrate intake. The analyses suggest that this dietary change over a sustained time period did not increase, and may have reduced, diabetes incidence and progression.
The WHI DMT intervention has been demonstrated to contribute to small, but significant, weight loss (1.9 kg loss in the intervention group compared with the control group at year 1, diminishing to 0.4 kg at the end of the intervention). In this analysis of progression of glucose intolerance, adjustment for weight loss had no impact on the findings in the overall group or in the subgroup analyses of women with or without central obesity, as measured by waist circumference. This observation suggests that the dietary intervention may have affected the sequence of events stemming from obesity and/or insulin resistance.
Prevailing diabetes treatments changed dramatically during the intervention period and do not represent current pharmacologic practices. For example, in women taking oral agents at baseline, metformin use tripled from baseline (17.5%) to year 6 (54.0%), thiazolidinedione use reached only 15% by year 6, and there was no reported usage of incretins or glucagon-like peptide 1 agonists.
In summary, in this secondary analysis of a trial in postmenopausal women, randomization to a behavioral intervention that promoted a low-fat diet (including higher vegetable, fruit, and grain intake) did not increase risk of diabetes. Rather, it may have been associated with reductions in glycemia and with the rate of diabetes therapy initiation and progression.
- The WHI DMT intervention has been demonstrated to contribute to small, but significant, weight loss (1.9 kg loss in the intervention group compared with the control group).
- The dietary intervention may have affected the sequence of events stemming from obesity and/or insulin resistance.
- Analysis of the intervention that promoted a low-fat diet (including higher vegetable, fruit, and grain intake) did not increase risk of diabetes.
Diabetes Care 2018 Apr; 41(4): 680-687. https://doi.org/10.2337/dc17-0534