Time restricted eating to treat gestational diabetes mellitus

Gestational diabetes mellitus (GDM) has an incidence of 2-5% in the
Netherlands, and confers an increased risk of maternal and neonatal
complications, including miscarriage, foetal anomalies, pre-eclampsia and
macrosomia. Blood glucose reduction reduces this risk of maternal and neonatal
complications in GDM.
All mammals have a circadian timing system, consisting of a central brain clock
in the hypothalamic suprachiasmatic nucleus (SCN), and peripheral clocks in
tissues including liver, muscle, and adipose tissue. The central SCN clock
regulates food intake and energy expenditure, and peripheral clocks regulate
daily rhythms in local tissue glucose metabolism, with the liver clock
regulating gluconeogenesis, the muscle clock regulating insulin sensitivity,
and the pancreas clock regulating insulin secretion. Peripheral clocks are not
only synchronized by direct signals from the central clock, but also strongly
respond to signals resulting from food intake. Time restricted eating (TRE) is
the reduction of the eating period to a consistent daily 4-12 hr period. The
rationale is that with appropriately timed TRE, the periods of food intake and
fasting are synchronized with the rhythm of the circadian timing system, and
thereby the functioning of the circadian tissue clocks is improved. Several
studies indicate that TRE is a promising new approach in the prevention and
treatment of diabetes mellitus. TRE protects against the development of
obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) in mice
fed a high fat diet, and in mice fed a high-fat-high-sucrose diet. In two
recent translational human pilot studies, 10-11hr TRE caused persistent weight
loss in 8 obese subjects and 6hr TRE improved insulin sensitivity in men with
prediabetes. To date, TRE has not been investigated in GDM. We hypothesize that
TRE improves insulin sensitivity, glucose values, and consequently neonatal and
maternal outcomes in GDM, via strengthening of clock gene expression rhythms.

To determine the effect of time restricted eating in gestational diabetes on
glucose metabolism.

prospective single blinded randomized controlled trial

The intervention group will adhere to a TRE-regimen in addition to receiving
the standard care as is given according to protocol in gestational diabetes
mellitus. The control group will solely be given the standard care according to
protocol.

The study will generate knowledge on the effects of time restricted eating on
sugar metabolism in women with GDM. This information is very valuable as GDM
with an incidence of 2-5% in the Netherlands confers an increased risk of
maternal and neonatal complications. Blood glucose reduction reduces this risk
of maternal and neonatal complications in GDM and TRE could prove to be a novel
way of achieving this. No benefits for the patients can be guaranteed but
adhering to a TRE-regimen in women with GDM could lead to a better glucose
control if similar results are found to an earlier study in men with
prediabetes.

Study burden an risks are in proportion to the benefits for both society and
participants themselves. Participants will be in the study from approximately
28 week pregnancy duration until 6 weeks after delivery (i.e. approximately 12
weeks).
Total study duration is 12 weeks but actual time spent on the study is limited
to five short visits.

The burden of participation is minimal. In addition to regular care,
participants will
- fill in the Munich Chronotype Questionnaire (MCTQ) and the chrono-nutrition
questionnaire (10 min) at inclusion.
- At baseline and at week 4, 8 and 12 after inclusion, participants will:
o Keep track of their daily food intake by means of a food diary.
o Wear a wrist-worn actigraph, with the look and feel of a regular watch
o Fill in the Pittsburgh Sleep Quality Index (a questionnaire which takes
approximately 5 minutes to complete)
o Collect buccal cytological brushes with 4-hourly intervals during the awake
hours. For this they use a non-invasive buccal swab, which has no risks for the
participants.
- At the start of the study, week 4 and the visit before the expected delivery
date.
o Wear a Dexcom G6 glucose monitor. (This is optional; additional permission is
asked in the informed consent form).
-At the start of the study, the visit before the expected delivery date and 6
weeks post-partum;
o undergo hepatic steatosis measurement with the FibroScan (2-5 min). The
FibroScan is a non-invasive ultrasound measurement without any risks for
participants (additional permission for this procedure is asked in the informed
consent form).
o After study completion, undergo an in depth interview about the
time-restricted eating regimen (30 minutes)