I read with great interest the clinical trial report by Jakubowicz et al. recently published in Diabetes Care (1). The authors demonstrated a large benefit in a group of patients with type 2 diabetes just by manipulating the frequency and distribution of meals throughout the day. The interesting findings were explained as suggestive of clock gene expression correction by means of shifting carbohydrate intake to the morning time. They performed mRNA expression assays to support this hypothesis.
I want to point to an alternative explanation that, although inextricably associated with the protocol of the study, may be addressed in future trials. With the intervention diet having only a small 200 kcal dinner, one could reason that this protocol is not very different from implementing an intermittent fasting regimen with a feeding window of 5.5 h (0930–1500 h), corresponding to a daily 18.5 h of fasting.
Fasting has received recent attention, but there is a lack of human trials of sufficient size or length and in diverse settings, and clinical experience is still limited. Popular versions are alternate-day fasting and the closely related 5:2 fasting (5 ad libitum, 2 fasting days weekly) (2). Trials with severely restricted calories for a few days per week have been shown to be equivalent to daily calorie restriction for weight loss and metabolic health but have not been consistently shown to be better. A daily feeding window of 4–8 h, with corresponding fasting of 16–20 h, has shown promise in animal models but has been scarcely studied in humans (3–5). One such trial included healthy young men and seemed to be superior to the control diet in decreasing fat mass while keeping the feeding window in the afternoon and evening (5). To the best of my knowledge, there are no human trials of a similar protocol in patients with diabetes.
It would be very interesting to see a trial with similar methodology to the present carefully conducted study (1) but using different times of day for distribution of calories, such as the bulk of calories at dinner rather than breakfast, and compare it with the current winner protocol of a large breakfast. This would greatly inform the discussion of which variable is most responsible for the metabolic benefit shown in the present trial (time of day vs. length of feeding window).
I can certainly agree that a diet with multiple small meals has no scientific support for patients with type 2 diabetes wishing to improve metabolic parameters, and recommendation of this approach should be abandoned in this setting. I end by again praising the authors for this great addition to the literature.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
