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High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial

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Aims/hypothesis: High-energy breakfast and reduced-energy dinner (Bdiet) significantly reduces postprandial glycaemia in obese non-diabetic individuals. Our objective was to test whether this meal schedule reduces postprandial hyperglycaemia (PPHG) in patients with type 2 diabetes by enhancing incretin and insulin levels when compared with high-energy dinner and reduced-energy breakfast (Ddiet). Methods: In a randomised, open label, crossover design performed in a clinic setting, 18 individuals (aged 30-70 years with BMI 22-35 kg/m(2)) with type 2 diabetes (<10 years duration) treated with metformin and/or diet were given either Bdiet or Ddiet for 7 days. Participants were randomised by a person not involved in the study using a coin flip. Postprandial levels of plasma glucose, insulin, C-peptide and intact and total glucagon-like peptide-1 (iGLP-1 and tGLP-1) were assessed. The Bdiet included 2,946 kJ breakfast, 2,523 kJ lunch and 858 kJ dinner. The Ddiet comprised 858 kJ breakfast, 2,523 kJ lunch and 2,946 kJ dinner. Results: Twenty-two individuals were randomised and 18 analysed. The AUC for glucose (AUCglucose) throughout the day was 20% lower, whereas AUCinsulin, AUCC-peptide and AUCtGLP-1 were 20% higher for the Bdiet than the Ddiet. Glucose AUC0-180min and its peak were both lower by 24%, whereas insulin AUC0-180min was 11% higher after the Bdiet than the Ddiet. This was accompanied by 30% higher tGLP-1 and 16% higher iGLP-1 levels. Despite the diets being isoenergetic, lunch resulted in lower glucose (by 21-25%) and higher insulin (by 23%) with the Bdiet vs Ddiet. Conclusions/interpretation: High energy intake at breakfast is associated with significant reduction in overall PPHG in diabetic patients over the entire day. This dietary adjustment may have a therapeutic advantage for the achievement of optimal metabolic control and may have the potential for being preventive for cardiovascular and other complications of type 2 diabetes. Trial registration ClinicalTrials.gov NCT01977833 Funding No specific funding was received for the study.
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ARTICLE
High-energy breakfast with low-energy dinner decreases overall
daily hyperglycaemia in type 2 diabetic patients: a randomised
clinical trial
Daniela Jakubowicz &Julio Wainstein &Bo Ahrén &
Yosefa Bar-Dayan &Zohar Landau &
Hadas R. Rabinovitz &Oren Froy
Received: 23 November 2014 /Accepted: 28 January 2015
#Springer-Verlag Berlin Heidelberg 2015
Abstract
Aims/hypothesis High-energy breakfast and reduced-energy
dinner (Bdiet) significantly reduces postprandial glycaemia
in obese non-diabetic individuals. Our objective was to test
whether this meal schedule reduces postprandial
hyperglycaemia (PPHG) in patients with type 2 diabetes by
enhancing incretin and insulin levels when compared with
high-energy dinner and reduced-energy breakfast (Ddiet).
Methods In a randomised, open label, crossover design per-
formed in a clinic setting, 18 individuals (aged 3070 years
with BMI 2235 kg/m
2
) with type 2 diabetes (<10 years du-
ration) treated with metformin and/or diet were given either
Bdiet or Ddiet for 7 days. Participants were randomised by a
person not involved in the study using a coin flip. Postprandial
levels of plasma glucose, insulin, C-peptide and intact and
total glucagon-like peptide-1(iGLP-1andtGLP-1)were
assessed. The Bdiet included 2,946 kJ breakfast, 2,523 kJ
lunch and 858 kJ dinner. The Ddiet comprised 858 kJ break-
fast, 2,523 kJ lunch and 2,946 kJ dinner.
Results Twenty-two individuals were randomised and 18
analysed. The AUC for glucose (AUC
glucose
) throughout the
day was 20% lower, whereas AUC
insulin
, AUC
C-peptide
and
AUC
tGLP-1
were 20% higher for the Bdiet than the Ddiet.
Glucose AUC
0180min
and its peak were both lower by 24%,
whereas insulin AUC
0180min
was 11% higher after the Bdiet
than the Ddiet. This was accompanied by 30% higher tGLP-1
and 16% higher iGLP-1 levels. Despite the diets being
isoenergetic, lunch resulted in lower glucose (by 2125%)
and higher insulin (by 23%) with the Bdiet vs Ddiet.
Conclusions/interpretation High energy intake at breakfast is
associated with significant reduction in overall PPHG in dia-
betic patients over the entire day. This dietary adjustment may
have a therapeutic advantage for the achievement of optimal
metabolic control and may have the potential for being pre-
ventive for cardiovascular and other complications of type 2
diabetes.
Trial registration ClinicalTrials.gov NCT01977833
Funding No specific funding was received for the study.
Keywords Breakfast .Clock .Diabetes .Dinner .GLP-1 .
Insulin .Timing
Abbreviations
Bdiet High-energy breakfast and reduced-energy dinner
Ddiet High-energy dinner and reduced-energy breakfast
iGLP-1 Intact glucagon-like peptide-1
PPHG Postprandial hyperglycaemia
tGLP-1 Total glucagon-like peptide-1
Introduction
Postprandial hyperglycaemia (PPHG) contributes 3170% to
HbA
1c
values [1] and is strongly associated with increased
cardiovascular risk in type 2 diabetes [2,3]. Therefore, post-
prandial glycaemia is an important treatment target in type 2
D. Jakubowicz (*):J. Wainstein :Y. B a r - D a y a n :Z. Landau
Diabetes Unit, E. Wolfson Medical Center, Sackler Faculty of
Medicine, Tel Aviv University, Holon 58100, Israel
e-mail: daniela.jak@gmail.com
B. Ahrén
Department of Clinical Sciences, Faculty of Medicine, Lund
University, Lund, Sweden
H. R. Rabinovitz:O. Froy (*)
Institute of Biochemistry, Food Science and Nutrition, The Robert H.
Smith Faculty of Agriculture, Food and Environment, The Hebrew
University of Jerusalem, Rehovot 76100, Israel
e-mail: oren.froy@mail.huji.ac.il
Diabetologia
DOI 10.1007/s00125-015-3524-9
diabetes. Post-meal glycaemia displays a clear circadian pat-
tern with a more prolonged and higher response to an identical
meal in the evening vs the morning [48]. This is achieved in
part by the circadian secretion and activity of enzymes and
hormones involved in the regulation of postprandial
glycaemia [913]. Indeed, the circadian clock controls
glucagon-like peptide 1 (GLP-1) secretion in intestinal L cells
[9], insulin secretion in beta cells [14,15], hepatic insulin
extraction [7] and insulin-dependent glucose transporter
GLUT 4 expression in skeletal muscle [10,13].
While the master clock is entrained to the lightdark cycles
[16], meal timing and feeding schedules exert strong
entraining effects on peripheral oscillators maintaining the in-
ternal synchrony of most metabolic processes [17,18].
Studies in animals and humans have shown that altered meal
timing, such as skipping breakfast or high energy intake at
dinner, are associated with disrupted clock gene expression,
increased lipogenesis, higher HbA
1c
and poor glycaemic con-
trol [4,1922]. In contrast, high-energy breakfast with no
dinner or time-restricted feeding reversed the impaired clock
gene expression, resulting in decreased plasma glucose and
triacylglycerol levels and reduced body weight in animal
models of obesity and type 2 diabetes [12,22,23]. The dif-
ferent effects of meals during the day may therefore be mod-
ulated by different energy loads to achieve optimal glucose
homeostasis. However, the effect of different meal timing
schedules on overall incretin, insulin and glycaemic excursion
during the entire day has not been previously explored in
individuals with type 2 diabetes. In this study, we assessed
the differential influence of two isoenergetic diets with differ-
ent meal timing schedules on PPHG over the entire day and
the corresponding changes in insulin and incretin hormones in
patients with type 2 diabetes. The two dietary schedules were
as follows: one with high-energy breakfast and lower-energy
dinner (Bdiet) and the other with high-energy dinner and
lower-energy breakfast (Ddiet).
Methods
Participants The study population initially included 22 individ-
uals who had type 2 diabetes for less than 10 years and an HbA
1c
level of 79% (5375 mmol/mol) on recruitment (Table 1).
Individuals aged 3070 years with BMI 2235 kg/m
2
were
included. None of the participants had impaired thyroid, renal
or liver function, pulmonary disease, psychiatric, immunologi-
cal or neoplastic diseases or severe diabetic complications, such
as cardiovascular disease, cerebrovascular disease, proliferative
diabetic retinopathy or gastroparesis and none had undergone
bariatric surgery. All participants were insulin-naive and patients
taking oral hypoglycaemic agents other than metformin were
excluded. Those on GLP-1 analogues or anorectic drugs or
those on steroid treatment were not allowed to participate. The
Helsinki Committee of the Wolfson Medical Center in Holon,
Israel approved the study. All the participants gave their
informed consent. The study was registered at
ClinicalTrials.gov (NCT01977833).
Study design This was a randomised, open-label, crossover-
within-subject clinical trial. Participants were randomised by a
person not involved in the study using a coin flip. We per-
formed two separate testing days each over the course of 14 h.
Test meals were provided in the clinic as breakfast, lunch and
dinner with energy and composition according to the assigned
diet schedule (Table 2). The participants consumed their meals
within 15 min, with breakfast at 08:00 hours, lunch at
13:00 hours and dinner at 19:00 hours. The diet during both
testing days provided a total daily energy intake of 6,276±
105 kJ (23% fat, 46% carbohydrates, 31% protein) with iden-
tical macronutrient content and composition, but different
meal timing distribution. The two meal timing schedules were
either breakfast diet (Bdiet) or dinner diet (Ddiet). The Bdiet
consisted of a large breakfast (2,946 kJ; 22% fat, 47% carbo-
hydrates, 31% protein), a medium-sized lunch (2,523 kJ; 23%
fat, 50% carbohydrates, 27% protein) and a small dinner
(858 kJ; 30% fat, 27% carbohydrates, 43% protein). This
was reversed in the Ddiet (858 kJ breakfast, 2,523 kJ lunch
and 2,946 kJ dinner). Participants followed the Bdiet and
Ddiet meal plans for 6 days at home prior to the intervention
day to prevent the pre-study meal pattern from influencing the
results. Participants were also asked to avoid alcohol and
excessive physical activity 6 days before each test day.
Participants ingested their last oral therapy 24 h before the test
day. Following a washout period of 2 weeks, the same proce-
dure was repeated on the second test day, with each participant
now crossed over to the opposite diet schedule.
Tabl e 1 Clinical and anthropometric characteristics
Characteristic
No. of patients 18
Sex (no. male/no. female) 8/10
Age (years) 57.8±4.7
Weight (kg) 76.8± 13.5
BMI (kg/m
2
) 28.1±2.9
Waist circumference (cm) 94± 5.8
Systolic BP (mmHg) 130.7±7.2
Diastolic BP (mmHg) 80.6±7.46
HbA
1c
(%) 7.6±0.4
HbA
1c
(mmol/mol) 59 ±2
Time since diagnosis of diabetes (years) 9.3± 5
Fasting blood glucose (mmol/l) 7.2± 0.5
Fasting plasma insulin (pmol/l) 49.3±9
Data are shown as nor as mean ± SE
Diabetologia
Meal challenges On the day of the meal challenge, each par-
ticipant reported to the laboratory at 07:00 hours after an over-
night fast. Participants were asked not to take glucose-
lowering medication during the test days and were instructed
to keep dietary logs. A dietitian reviewed these logs on the day
of the meal tests and only those who had 80% adherence to the
diet participated in the meal tests. Anthropometric data were
collected in the morning and each group consumed their
assigned meal plan: breakfast at 08:00 hours, lunch at
13:00 hours and dinner at 19:00 hours. At 07:30 hours, a
catheter was placed in the antecubital vein of the non-
dominant arm and remained in place until 22:00 hours.
Venous blood samples were collected just before breakfast
(t=0 min) and at 15, 30, 60, 90, 120, 150 and 180 min after
eating commenced. Blood sampling was repeated at the same
time points after lunch and dinner. The primary outcome was
to assess the overall postprandial GLP-1 levels in both meal
schedules. The secondary outcome was to assess the overall
postprandial glycaemia. Other outcomes were to assess the
overall postprandial response of plasma insulin and
C-peptide in both meal schedules.
Biochemical and hormonal blood analyses Plasma glucose
was immediately analysed on an Olympus AU 2700
analyser (Beckman Coulter, Brea, CA, USA). Serum and
plasma EDTA tubes for insulin and C-peptide were left on
ice to rest for approximately 30 min. Blood samples for
determining iGLP-1 and tGLP-1 were collected into
chilled tubes containing EDTA, aprotinin and diprotin A
(0.1 mmol/l). Samples were centrifuged immediately at
2,000gat 4°C for 10 min and stored at 80°C. Insulin and
C-peptide were determined by electrochemiluminescence
using a Cobas 601 Roche Diagnostic analyser (Madison,
WI, USA) according to the manufacturers instructions.
Tabl e 2 Diet composition on the meal test days
Meal type Energy content (kJ) Composition
Fat (g) Carbohydrate (g) Protein (g) Fibre (g)
Large meal
Whole-wheat bread: two slices 569 2.4 25.8 5.4 3.9
Caffè latte with non-fat milk: one tall 418 0.0 15.0 10.0 0.0
Tuna, light in water: 115 g 502 1.0 1.0 26.0 0.4
Scrambled egg: one egg 159 1.5 0.5 5.5 0.0
Olive oil: two teaspoons 335 9.0 0.0 0.0 0.0
Yogurt and cereal: one container 460 2.0 20.0 5.0 3.0
Granola bar, dark chocolate: one bar 502 2.0 24.0 5.0 4.0
Total 2,946 17.9 86.3 56.9 11.3
Percentage of energy 22 47 31 -
Lunch
Apple: one apple 339 0.5 21.0 0.3 3.7
Roasted chicken breast: 115 g 782 4.0 0.0 35.0 0.0
Diet drink: 236 ml 0 0.0 0.0 0.0 0.0
Salad, tossed greens: one salad 42 0.0 2.0 0.0 0.5
Vegetable soup: one cup 418 2.0 20.0 4.0 4.0
Olive oil: two teaspoons 335 9.0 0.0 0.0 0.0
Baked potato: one potato 607 0.2 33.6 3.1 2.3
Total 2,523 15.7 76.6 42.4 10.5
Percentage of energy 23 50 27 -
Small meal
Caffè Americano: one large 63 0.0 3.0 1.0 0.0
Salad, fresh tomato and mozzarella: one order 469 7.0 6.0 6.2 1.0
Salad, tossed greens: one salad 42 0.0 2.0 0.0 0.5
Turkey breast: three slices 251 0.0 1.0 14.0 -
Salad, mixed greens: one cup 33 0.0 2.0 1.0 1.0
Total 858 7.0 14.0 22.2 2.5
Percentage of energy 30 27 43 -
Diabetologia
Plasma tGLP-1 and iGLP-1 were quantified using ELISA
(Millipore, Billerica, MA, USA).
Sample size and power analysis Power analysis revealed that
a sample size of 18 participants (18 in each treatment group;
Bdiet and Ddiet) is required to provide 80% power to detect
5% difference between groups in overall postprandial plasma
AUC for iGLP-1, insulin and glucose assessed after three
meals in each diet intervention. To allow discontinuation dur-
ing the course of the study, 22 participants were recruited.
Statistical analyses The results are expressed as mean ±SEM.
For time series, a two-way ANOVA (time ×diet) was per-
formed and a least-significant difference ttest post hoc analy-
sis was used for comparison between the diets at each time
point. Means comparisons were made using the CI of the
estimators. AUCs were calculated using the trapezoidal rule.
AStudentsttest for paired data was used for comparing the
AUC at different time intervals. In addition, a multivariate
ANOVA for repeated measurements was performed to assess
between- and within-subject effects for diet and time. A
pvalue 0.05 was considered statistically significant.
Statistical analysis was performed using SPSS (version 18)
software (www14.software.ibm.com/download/data/web/en_
US/trialprograms/W110742E06714B29.html).
Results
Participants Twenty-two individuals from the Wolfson
Diabetes Unit outpatient clinic were enrolled into the study
(Fig. 1). The study period from recruitment and including
follow-up was December 2013 to April 2014. After complet-
ing the first all-meals testing day, four participants dropped out
(two from the Bdiet group and two from the Ddiet group),
because of difficulties getting to the clinic. Eighteen individ-
uals (eight men, ten women) completed the study. These pa-
tients had an average age of 57.8 ±4.7 years, controlled type 2
diabetes of 9.3±5.0 years duration, HbA
1c
values of 7.6±
0.4% (59±2 mmol/mol) and BMI of 28.1±2.9 kg/m
2
(Table 1). Eight patients were treated with diet alone, whereas
ten were treated with diet and metformin. Five patients had a
history of hypertension and were treated with thiazides,
angiotensin-converting enzyme inhibitors and/or calcium
antagonists.
Plasma glucose and hormonal profiles of Bdiet vs Ddiet
group Fasting plasma glucose, insulin, C-peptide, tGLP-1
and iGLP-1 did not differ significantly between the two test
days or the groups (Fig. 2). Integrated AUC
glucose
after break-
fast, lunch and dinner was 20% lower in the Bdiet group than
in the Ddiet ( p<0.001, ttest) group (Fig. 2). Integrated
Assessed for eligibility (n=22)
Excluded (n=0)
Not meeting inclusion criteria (n=0)
Declined to participate (n=0)
Other reasons (n=0)
Analysed (n=18)
Excluded from analysis: discontinued
intervention (n=2)
Lost to follow-up (n=0)
Discontinued intervention: difficulty arriving at
clinic (n=2)
Allocated to receive Bdiet (n=22)
Received allocated intervention (n=22)
Did not receive allocated intervention (n=0)
Lost to follow-up (give reasons) (n=0)
Discontinued intervention: difficulty arriving at
clinic (n=2)
Allocated to receive Ddiet (n=22)
Received allocated intervention (n=22)
Did not receive allocated intervention (n=0)
Analysed (n=18)
Excluded from analysis: discontinued
intervention (n=2)
Allocation
Analysis
Follow-up
Randomised (n=22)
Enrolment
Fig. 1 Flow diagram of
recruitment
Diabetologia
AUC
insulin
,AUC
C-peptide
and AUC
tGLP-1
after breakfast, lunch
and dinner were higher by 20% during the Bdiet than during
the Ddiet ( p<0.001, ttest). Integrated AUC
iGLP-1
after break-
fast, lunch and dinner was higher by 10% during the Bdiet
than during the Ddiet (p<0.001, ttest).
Plasma glucose and hormonal profiles after high-energy
breakfast vs high-energy dinner After high-energy breakfast,
glucose AUC
0180min
and its peak were reduced by 24% com-
pared with the glucose response after high-energy dinner
(p<0.001, ttest) (Table 3, Fig. 2). During the early interval,
AUC
030min
, plasma glucose was lower by 10% after high-
energy breakfast vs high-energy dinner ( p<0.006, ttest).
After reaching their peak, plasma glucose levels decreased
rapidly after the high-energy breakfast whereas after the
high-energy dinner, plasma glucose persisted and remained
significantly higher.
The insulin response to the meal challenge was more rapid
and higher after high-energy breakfast compared with high-
energy dinner (Table 3,Fig.2). Insulin AUC
0180min
was 11%
higher after high-energy breakfast than after high-energy din-
ner ( p<0.001, ttest) (Table 3). During the first 30 min, plasma
insulin levels increased more rapidly after high-energy break-
fast than after high-energy dinner ( p<0.008, ttest). During
the late interval, AUC
60180min
, insulin secretion did not differ
(p<0.11) between the meals. After high-energy breakfast,
peak insulin secretion occurred at 60 min, 12% higher
(p<0.002, ttest) than after high-energy dinner. After high-
energy dinner, peak insulin secretion occurred at 120 min.
After meal ingestion, patterns of C-peptide levels mirrored
those of insulin with a more rapid and higher increase after
high-energy breakfast. High-energy breakfast resulted in a
higher C-peptide early response and AUC
0180min
, by 17%
(p<0.001, ttest) compared with high-energy dinner (Table 3).
The AUC
0180min
for tGLP-1 was 29% higher after high-
energy breakfast than after high-energy dinner ( p< 0.001,
ttest) (Table 3,Fig.2). Plasma tGLP-1 increased rapidly after
high-energy breakfast and peaked at 30 min. In contrast, after
high-energy dinner, the increase in plasma tGLP-1 was more
gradual and peaked at 60 min. Compared with high-energy
dinner, the high-energy breakfast resulted in 21% higher
tGLP-1 levels ( p<0.001, post hoc ttest). The high-energy
breakfast elicited 3035% higher early and late interval for
tGLP-1 ( p< 0.001, ttest). Similarly, iGLP-1 plasma levels
peaked at 30 min after high-energy breakfast compared with
a peak at 60 min after high-energy dinner. The peak level of
iGLP-1 was higher by 16% after high-energy breakfast than
after high-energy dinner ( p<0.001, post hoc ttest). The
AUC
0180min
, as well as the early and late intervals for
tGLP-1 and iGLP-1, were 1435% higher after high-energy
breakfast than after high-energy dinner ( p<0.001, ttest).
Plasma glucose and hormonal profiles after Bdiet lunch vs
Ddiet lunch Glucose AUC
0180min
and its peak were lower
by 2125% after Bdiet lunch vs Ddiet lunch ( p<0.001, ttest)
(Table 3, Fig. 2). The glucose early and late interval was lower
by 13% and 24%, respectively, after Bdiet lunch than after
Ddiet lunch ( p<0.006,ttest). Insulin AUC
0180min
was higher
by 23% after Bdiet lunch than after Ddiet lunch. In addition,
0
2
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AUCiGLP-1 (pmol/l × min)
AUCtGLP-1 (pmol/l × min) AUCC-peptide (nmol/l × min)
iGLP-1 (pmol/l)
AUCinsulin (pmol/l × min) AUCglucose (mmol/l × min)
tGLP-1 (pmol/l) C-peptide (nmol/l) Insulin (pmol/l) Glucose (mmol/l)
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Fig. 2 All-day graphs for glucose, insulin, C-peptide, tGLP-1 and iGLP-
1. White circles, Ddiet group; black circles, Bdiet group. *p<0.05
Diabetologia
the early prandial insulin AUC
030min
was higher by almost
50% after Bdiet lunch vs Ddiet lunch ( p<0.001,ttest). Insulin
reached peak levels 30 min after the Bdiet lunch and 90 min
after the Ddiet lunch, with the Bdiet lunch producing higher
peak levels ( p<0.001, ttest) (Table 3, Fig. 2). Throughout the
180 min of analysis, C-peptide levels were 30% higher after
the Bdiet lunch than after the Ddiet lunch ( p<0.001, ttest)
and tGLP-1 and iGLP-1 levels were 1626% higher after the
Bdiet lunch than after the Ddiet lunch ( p<0.001, ttest). In
addition, tGLP-1 and iGLP-1 peaked 30 min earlier after
Bdiet lunch compared with Ddiet lunch.
Discussion
In this study, we demonstrate in individuals with type 2 dia-
betes that a meal schedule of high-energy breakfast and low-
energy dinner (Bdiet) leads to overall increased GLP-1 and
insulin levels and to reduced hyperglycaemia throughout the
day compared with a reverse meal schedule (Ddiet). Although
both diets had an identical day-long energy composition, the
difference in timing led to a significant reduction in overall
glucose excursions in the Bdiet compared with the Ddiet. In
parallel, the integrated AUCs for insulin, C-peptide, iGLP-1
and tGLP-1 secretion were significantly enhanced along the
entire day in the Bdiet compared with the Ddiet schedule.
These observations suggest that a change in meal timing
influences the overall daily rhythm of postprandial insulin,
incretin and glycaemic excursions. Our findings showing a
significantly reduced overall glycaemia with the Bdiet sched-
ule are consistent with studies in animal models. Impaired
peripheral clock gene expression as a result of breakfast skip-
ping or reduced food intake in the first meal of the day along
with high-energy dinner, has been associated with increased
lipogenesis and higher overall daily glucose excursions, de-
spite no differences in daily total or fat-derived energy [12,
22]. Alternatively, a specific change in the meal timing (i.e.
increasing breakfast and reducing dinner energy content) may
also restore clock gene expression in obese and diabetic ani-
mals, resulting in reduced plasma glucose and triacylglycerol
levels and body weight [12,22]. Recently, it was reported that
high-energy breakfast with reduced dinner improved insulin
sensitivity and decreased body weight, glucose excursions and
HbA
1c
among obese and diabetic patients [2427]. The omis-
sion of breakfast was also associated with increased risk of
type 2 diabetes, poor glycaemic control, higher HbA
1c
, in-
creased lipogenesis, visceral adiposity and high blood pres-
sure and increased cardiovascular risk despite the same daily
energy intake in individuals with type 2 diabetes [20,21].
Although this study investigated the acute effect of meals,
long-term interventions should determine whether adhering
to this diet would successfully lower HbA
1c
levels. This issue
was addressed in our previous study, in which eating a large
breakfast each day for 3 months led to a 5% reduction in
Tabl e 3 AUC at different time intervals of breakfast vs dinner and HE lunch of Bdiet vs Ddiet
AUC Bdiet HE breakfast Ddiet HE dinner pvalue % change Bdiet lunch Ddiet lunch pvalue % change
Glucose (mmol/l×min)
030 min 283± 16 311±27 <0.006 10 243± 6 275 ±16 <0.001 13
60180 min 1,094 ±56 1,513±125 <0.001 27 1,038±55 1,368±124 <0.001 24
0180 min 1,735±76 2,270±167 <0.001 24 1,586± 9 2,015 ±67 <0.001 21
Insulin (pmol/l ×min)
030 min 3,653±757 3,104±326 <0.008 19 6,587±590 3,327± 382 <0.001 49
60180 min 28,308 ±2,952 26,780 ±3,702 0.111 8 25,683± 3,841 24,155±3,118 0.140 8
0180 min 38,753± 3,695 34,572± 4,257 <0.001 11 41,781±4,424 32,260±3,792 <0.001 23
C-peptide (nmol/l×min)
030 min 31± 7 26 ±5 0.042 17 50± 7 33± 5 <0.001 35
60180 min 22 19 194± 15 <0.001 16 236±36 170 ±25 <0.001 28
0180 min 300±29 250 ±20 <0.001 17 354±43 249± 23 <0.001 30
tGLP-1 (pmol/l ×min)
030 min 817 ±104 533± 51 <0.001 35 906.1 ±89 519.7±115 <0.001 43
60180 min 3,178 ±388 2,238± 241 <0.001 30 3,271 ±453 2,566± 352 <0.001 22
0180 min 5,063±489 3,581±256 <0.001 29 5,298 ±523 3,938± 490 <0.001 26
iGLP-1 (pmol/l ×min)
030 min 347 ±36 255 ±27 <0.001 27 391.3±26 265.5±22 <0.001 32
60180 min 1,403 ±124 1,202± 133 <0.001 14 1,431 ±161 1,294± 104 <0.002 11
0180 min 2,183±154 1,799±161 <0.001 18 2,286 ±64 1,931±113 <0.001 16
Diabetologia
HbA
1c
levels [27]. Thus, meal timing schedule may be a
crucial factor in the improvement of glucose balance and
prevention of complications in type 2 diabetes and lends
further support to the role of the circadian system in meta-
bolic regulation.
The postprandial glucose response after the high-energy
breakfast was significantly lower than after the low-energy
breakfast, and decreased rapidly after the peak at 30 min. In
contrast, the plasma glucose after high-energy dinner peaked
higher than after the low-energy dinner, and remained elevat-
ed until the end of the postprandial response. Decline in car-
bohydrate tolerance toward the evening, with more prolonged
and higher postprandial glycaemic response to identical meals
in the evening than in the morning has been shown in healthy
individuals and those with type 2 diabetes [48]. Notably, the
2 h post-meal glycaemia was significantly lower after the
high-energy breakfast than after the high-energy dinner, and
was below the upper limit (10 mmol/l) of 2 h post-meal
glycaemia recommended in the recent ADA guidelines for
the prevention of cardiovascular events in patients with type
2 diabetes. In parallel, significantly higher insulin and
C-peptide responses were observed after the high-energy
breakfast than after the high-energy dinner. This greater and
more rapid early prandial insulin secretion after the high-
energy breakfast has further importance since in type 2 diabe-
tes the deficiency of early prandial insulin is the major con-
tributor to postprandial hyperglycaemia and cardiovascular
risk [2,3]. The mechanism of better glucose tolerance after
high-energy breakfast than after an identical dinner may be in
part the result of clock regulation that triggers higher beta cell
responsiveness in the morning, lower hepatic insulin extrac-
tion after breakfast than after dinner [7]andtheincreasein
insulin-mediated muscle glucose uptake in the morning [7,
10]. Thus, the assignment of major energy load at breakfast,
when beta cell responsiveness and insulin-mediated muscle
glucose uptake are at optimal levels, seems an adequate strat-
egy to decrease PPHG in patients with type 2 diabetes. The
contribution to our results made by different clearance of in-
sulin cannot be excluded, although ratios of insulin to
C-peptide (a rough estimate of hepatic extraction) did not
differ between the diets.
The early prandial increase in GLP-1 during the first
30 min after high-energy breakfast coincided with the early
prandial insulin response. These results are supported by pre-
vious findings in which AUC30
iGLP-1
correlated significantly
with AUC30
insulin
[6]. This suggests that the more rapid and
higher early insulin response after the high-energy breakfast
may be a result of a more rapid early prandial GLP-1 level,
which mediates the potentiation of beta cell function.
Recently, the circadian rhythm of GLP-1 secretory responses
was shown in animals, with increased release after the first
meal at the beginning of the normal feeding period and this
profile was correlated with insulin secretion [9]. Moreover,
when this first meal was omitted, both GLP-1 and insulin
rhythms were completely inverted along with disruption of
clock gene expression. Collectively, these results indicate that
the peripheral clock in intestinal L cells, which drives the
circadian expression of GLP-1, can be modulated by different
meal timing.
Glucose excursions were reduced after lunch preceded by
high-energy breakfast (Bdiet) compared with after an identical
lunch preceded by low-energy breakfast (Ddiet). This reduced
glucose response was associated with rapid and significantly
enhanced insulin, tGLP-1 and iGLP-1 responses. This second-
meal phenomenon suggests that by changing meal timing
schedule, it is possible to enhance the incretin and
insulinotropic effects, achieving significant reduction in
PPHG through the day in patients with type 2 diabetes.
Several theories have been suggested to explain the
second-meal phenomenon in type 2 diabetes, including
differences in the amount and the pattern of insulin secre-
tion, augmentation of beta cell function and increased
incretin response [26,28]. The high GLP-1 response to
lunch after high-energy breakfast suggests that incretin
hormones may play an important role in the second-meal
phenomenon. Indeed, this phenomenon was absent after a
repeated intravenous glucose tolerance test [29], but not
after a meal tolerance test [26,30,31].
One limitation of our study is that the macronutrient com-
position varied according to the time of day. Thus, some of the
results may also be due to the timing of macronutrient inges-
tion. Another limitation is that a group of healthy individuals
was not included. Although we show the effect of two differ-
ent meal timing schedules on the overall hyperglycaemia and
on the potentiation of insulin and incretin secretion throughout
the day and the effect of second-meal phenomenon in diabetic
individuals, we cannot determine whether these effects also
occur in healthy people. In addition, insulin sensitivity, sup-
pression of endogenous glucose production and gastric emp-
tying were not examined.
In conclusion, the results of this study support a role for
diurnal regulation in glycaemic control in patients with type 2
diabetes. We demonstrated that a larger percentage of daily
energy consumed at breakfast is associated with significant
reduction in overall PPHG in patients with type 2 diabetes.
The findings also suggest the possibility of applying the
second-meal phenomenon as a way of reducing postpran-
dial glucose excursion, especially at lunch. This, along
with the benefits of the Bdiet schedule in reducing overall
hyperglycaemia, may have a therapeutic advantage for the
achievement of optimal metabolic control and may pre-
vent cardiovascular and other complications of type 2
diabetes.
Acknowledgement The authors would like to thank M. Barnea (The
Weizmann Institute of Science, Rehovot, Israel) for statistical assistance.
Diabetologia
Duality of interest The authors declare that there is no duality of inter-
est associated with this manuscript.
Contribution statement JW contributed to the conception and design
of the study, acquired and interpreted data and drafted the article. OF and
DJ contributed to the conception and design of the study, acquired,
analysed and interpreted data and drafted and revised the article. BA
researched data, contributed to the interpretation of the data and drafted
and revised the article. HRR, YB and ZL contributed to the conception
and design of the study, acquired and interpreted data, organised the
randomisation and drafted the article. Alllisted authors approved the final
version of the manuscript. DJ is the guarantor of this work.
References
1. Monnier L, Lapinski H, Colette C (2003) Contributions of fasting
and postprandial plasma glucose increments to the overall diurnal
hyperglycemia of type 2 diabetic patients: variations with increasing
levels of HbA(1c). Diabetes Care 26:881885
2. Ceriello A, Colagiuri S, Gerich J, Tuomilehto J, Guideline
Development G (2008) Guideline for management of
postmeal glucose. Nutrition, metabolism, and cardiovascular
diseases. Nutr Metab Cardiovasc Dis 18:S17S33
3. Szuszkiewicz-Garcia MM, Davidson JA (2014) Cardiovascular
disease in diabetes mellitus: risk factors and medical therapy.
Endocrinol Metab Clin N Am 43:2540
4. Morgan LM, Shi JW, Hampton SM, Frost G (2012) Effect of meal
timing and glycaemic index on glucose control and insulin secretion
in healthy volunteers. Br J Nutr 108:12861291
5. van Cauter E, Shapiro ET, Tillil H, Polonsky KS (1992) Circadian
modulation of glucose and insulin responses to meals: relationship to
cortisol rhythm. Am J Physiol 262:E467E475
6. Lindgren O, Mari A, Deacon CF et al (2009) Differential islet and
incretin hormone responses in morning versus afternoon after stan-
dardized meal in healthy men. J Clin Endocrinol Metab 94:2887
2892
7. Saad A, Dalla Man C, Nandy DK et al (2012) Diurnal pattern to
insulin secretion and insulin action in healthy individuals. Diabetes
61:26912700
8. Gibbs M, Harrington D, Starkey S, Williams P, Hampton S (2014)
Diurnal postprandial responses to low and high glycaemic index
mixed meals. Clin Nutr 33:889894
9. Gil-Lozano M, Mingomataj EL, Wu WK, Ridout SA, Brubaker PL
(2014) Circadian secretion of the intestinal hormone GLP-1 by the
rodent L cell. Diabetes 63:36743685
10. Dyar KA, Ciciliot S, Wright LE et al (2014) Muscle insulin sensitiv-
ity and glucose metabolism are controlled by the intrinsic muscle
clock. Mol Metab 3:2941
11. Froy O (2010) Metabolism and circadian rhythmsimplications for
obesity. Endocr Rev 31:124
12. Wu T, Sun L, ZhuGe F et al (2011) Differential roles of breakfast and
supper in rats of a daily three-meal schedule upon circadian regula-
tion and physiology. Chronobiol Int 28:890903
13. Prasai MJ, Mughal RS, Wheatcroft SB, Kearney MT, Grant PJ, Scott
EM (2013) Diurnal variation in vascular and metabolic function in
diet-induced obesity: divergence of insulin resistance and loss of
clock rhythm. Diabetes 62:19811989
14. Yoshino J, Imai S (2010) A clock ticks in pancreatic beta
cells. Cell Metab 12:107108
15. Sadacca LA, Lamia KA, deLemos AS, Blum B, Weitz CJ (2011) An
intrinsic circadian clock of the pancreas is required for normal insulin
release and glucose homeostasis in mice. Diabetologia 54:120124
16. Reppert SM, Weaver DR (2002) Coordination of circadian timing in
mammals. Nature 418:935941
17. Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F,
Schibler U (2000) Restricted feeding uncouples circadian oscillators
in peripheral tissues from the central pacemaker in the suprachias-
matic nucleus. Genes Dev 14:29502961
18. Hara R, Wan K, Wakamatsu H et al (2001) Restricted feeding en-
trains liver clock without participation of the suprachiasmatic nucle-
us. Genes Cells 6:269278
19. Loboda A, Kraft WK, Fine B et al (2009) Diurnal variation of the
human adipose transcriptome and the link to metabolic disease.
BMC Med Genomics 2:7
20. Reutrakul S, Hood MM, Crowley SJ, Morgan MK, Teodori M,
Knutson KL (2014) The relationship between breakfast skipping,
chronotype, and glycemic control in type 2 diabetes. Chronobiol Int
31:6471
21. Mekary RA, Giovannucci E, Willett WC, van Dam RM, Hu FB (2012)
Eating patterns and type 2 diabetes risk in men: breakfast omission,
eating frequency, and snacking. Am J Clin Nutr 95:11821189
22. Fuse Y, Hirao A, Kuroda H, Otsuka M, Tahara Y, Shibata S (2012)
Differential roles of breakfast only (one meal per day) and a
bigger breakfast with a small dinner (two meals per day) in
mice fed a high-fat diet with regard to induced obesity and
lipid metabolism. J Circadian Rhythms 10:4
23. Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O (2012)
Timed high-fat diet resets circadian metabolism and prevents obesity.
FASEB J 26:34933502
24. Jakubowicz D, Froy O, Wainstein J, Boaz M (2012) Meal
timing and composition influence ghrelin levels, appetite
scores and weight loss maintenance in overweight and obese
adults. Steroids 77:323331
25. Jakubowicz D, Barnea M, Wainstein J, Froy O (2013) High
caloric intake at breakfast vs. dinner differentially influences
weight loss of overweight and obese women. Obesity 21:
25042512
26. Jakubowicz D, Froy O, Ahrén B et al (2014) Incretin, insulinotropic
and glucose-lowering effects of whey protein pre-load in type 2 dia-
betes: a randomised clinical trial. Diabetologia 57:18071811
27. Rabinovitz HR, Boaz M, Ganz T et al (2014) Big breakfast rich in
protein and fat improves glycemic control in type 2 diabetics. Obesity
22:E46E54
28. Lee SH, Tura A, Mari A et al (2011) Potentiation of the early-phase
insulin response by a prior meal contributes to the second-meal phe-
nomenon in type 2 diabetes. Am J Physiol Endocrinol Metab 301:
E984E990
29. Ravanam A, Jeffery J, Nehlawi M, Abraira C (1991) Improvement of
glucose-primed intravenous glucose tolerance and correction of acute
insulin decrement by glipizide in type II diabetes. Metab Clin Exp 40:
11731177
30. Jovanovic A, Gerrard J, Taylor R (2009) The second-meal phenom-
enon in type 2 diabetes. Diabetes Care 32:11991201
31. Bonuccelli S, Muscelli E, Gastaldelli A et al (2009) Improved
tolerance to sequential glucose loading (Staub-Traugott effect):
size and mechanisms. Am J Physiol Endocrinol Metab 297:
E532E537
Diabetologia
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... Des rapports récents suggèrent que la consommation d'un petit déjeuner riche en calories (500 kcal), avec un apport calorique plus faible au diner (200 kcal) entraîne une amélioration plus prononcée de la glycémie à jeun, du taux d'insuline et des scores de satiété qu'une répartition calorique inverse chez des sujets en surpoids et obèses [259]. On retrouve cela également chez les patients atteints de DT2 avec une diminution des hyperglycémies quotidiennes globales suite à un petit déjeuner riche et un diner faible en calories [260].Si l'on s'intéresse au fractionnement alimentaire, la majorité des études d'intervention ne rapportent pas ou peu d'impact bénéfique de l'augmentation de la fréquence des repas sur le poids corporel [261][262][263], le bilan énergétique et la santé [263], en condition isocalorique ou hypocalorique chez des sujets sains ou obèses. A l'inverse, sur les aspects de la satiété, Allirot et al., dans une étude contrôlée, ont montré un effet favorable du fractionnement alimentaire aigu sur les différents aspects de la satiété chez le sujet obèse [264]. ...
Thesis
L’hyperglycémie chronique est impliquée dans le développement de complications associées au DT2 et la variabilité glycémique (VG) apparait comme une composante à part entière de l'homéostasie du glucose. Les mesures hygiéno-diététiques, en première ligne dans la prise en charge du DT2, passent entre autres par une modification de l’alimentation, dans laquelle les glucides occupent une place prépondérante. Au-delà de la quantité, la qualité des glucides a été mise en avant comme ayant un impact déterminant sur les excursions glycémiques. Notamment, la digestibilité des produits à base d’amidon pourrait alors avoir un impact sur le contrôle glycémique chez les patients atteints de DT2. Mais il y a aujourd’hui un réel besoin d’apporter une caractérisation des produits plus complète sur cet aspect et de mener des études de faisabilité et d’efficacité de tels régimes modulant la digestibilité de l’amidon. Mes travaux de thèse montrent qu’il est possible de concevoir un régime riche en amidon lentement digestible (SDS), grâce à des choix de produits amylacés disponibles dans le commerce, des conseils de cuisson et des recommandations adaptées. Pour la première fois, nous avons montré que le contrôle de la digestibilité de l'amidon de produits amylacés avec des instructions de cuisson appropriées dans une population atteinte de DT2 augmentait la consommation de contenu en SDS dans un contexte de vie réelle et que ce type de régime était bien accepté dans telle population. De plus, nous avons montré que l’augmentation du rapport SDS/glucides était associée à une amélioration du contrôle glycémique postprandial et qu’il existait une corrélation linéaire inverse entre les paramètres de VG et la teneur en SDS. La mise en œuvre d’un régime riche en amidon lentement digestible dans une population atteinte de DT2, a montré une différence significative sur le profil de variabilité glycémique, mais également sur les excursions glycémiques postprandiales, évalués par le CGMS, en comparaison avec un régime pauvre en amidon lentement digestible. Ce type de régime a également permis aux patients d’atteindre des cibles glycémiques postprandiales plus appropriées. Grâce à un travail de revue de la littérature, nous avons mis en évidence que la déviation standard (SD), le coefficient de variation (CV), l’amplitude moyenne des excursions glycémiques (MAGE) et la moyenne glycémique (MBG) étaient les paramètres de VG les plus étudiés en termes de relation avec les paramètres de diagnostic du DT2 et les complications liées au DT2 et qu’ils montraient des relations fortes, en particulier avec l’HbA1c. Dans les études interventionnelles, nous avons pu voir que la SD, le MAGE et le temps dans la cible (TIR) étaient les paramètres les plus utilisés comme critères d’évaluation, montrant des améliorations significatives suite aux interventions pharmacologiques ou nutritionnelles, souvent en lien avec des paramètres de contrôle glycémique comme l’HbA1c, la glycémie à jeun ou en postprandial. La VG apparaît donc comme une composante clé de la dysglycémie du DT2. Au-delà de son utilisation par le patient comme support du contrôle glycémique, le CGMS apparait comme un outil pertinent en recherche clinique pour évaluer l’efficacité des interventions même si à ce jour, il reste encore très peu utilisé pour les interventions nutritionnelles. Des études plus approfondies seront cependant nécessaires pour confirmer l'impact bénéfique de telles interventions alimentaires à long terme. Nous avons conçu une étude à plus grande échelle pour étudier l'impact à long terme d’un régime riche en SDS sur la variabilité et le contrôle glycémiques (CGMS) et les complications et comorbidités associées chez le patient atteint de DT2. La modulation de la digestibilité de l'amidon dans l'alimentation pourrait alors être utilisée comme un outil nutritionnel simple et approprié pour améliorer l'homéostasie glucidique au quotidien dans le DT2.
... The TRE studies that have utilized meal photo timing have provided a comprehensive analysis of the number of eating occasions (as a surrogate measure of total EI) and reported a reduction (14,18) or similar number (43), in response to the reduced eating window. Evidence from studies by Jakubowicz and colleagues (44,45) has shown that larger morning meals (high in carbohydrate) with small evening meals (high in protein) are effective for reducing body weight and improving glycemic control. However, in these studies, it is difficult to determine whether it is the EI or the macronutrient distribution that led to changes in several physiological outcomes. ...
Article
Time-restricted eating (TRE) is a popular dietary strategy that emphasises the timing of meals in alignment with diurnal circadian rhythms, permitting ad libitum energy intake during a restricted (∼8-10 h) eating window each day. Unlike energy-restricted diets or intermittent fasting interventions that focus on weight loss, many of the health-related benefits of TRE are independent of reductions in body weight. However, TRE research to date has largely ignored what food is consumed (i.e., macronutrient composition and energy density), overlooking a plethora of past epidemiological and interventional dietary research. To determine some of the potential mechanisms underpinning the benefits of TRE on metabolic health, future studies need to increase the rigour of dietary data collected, assessed, and reported to ensure a consistent and standardised approach in TRE research. This perspective provides an overview of studies investigating TRE interventions in humans and considers dietary intake (both what and when food is eaten) and their impact on selected health outcomes (i.e., weight loss, glycaemic control). Integrating existing dietary knowledge about what food is eaten with our recent understanding on when food should be consumed is essential to optimise the impact of dietary strategies aimed at improving metabolic health outcomes.
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Importance: It is unclear how effective intermittent fasting is for losing weight and body fat, and the effects may depend on the timing of the eating window. This randomized trial compared time-restricted eating (TRE) with eating over a period of 12 or more hours while matching weight-loss counseling across groups. Objective: To determine whether practicing TRE by eating early in the day (eTRE) is more effective for weight loss, fat loss, and cardiometabolic health than eating over a period of 12 or more hours. Design, setting, and participants: The study was a 14-week, parallel-arm, randomized clinical trial conducted between August 2018 and April 2020. Participants were adults aged 25 to 75 years with obesity and who received weight-loss treatment through the Weight Loss Medicine Clinic at the University of Alabama at Birmingham Hospital. Interventions: All participants received weight-loss treatment (energy restriction [ER]) and were randomized to eTRE plus ER (8-hour eating window from 7:00 to 15:00) or control eating (CON) plus ER (≥12-hour window). Main outcomes and measures: The co-primary outcomes were weight loss and fat loss. Secondary outcomes included blood pressure, heart rate, glucose levels, insulin levels, and plasma lipid levels. Results: Ninety participants were enrolled (mean [SD] body mass index, 39.6 [6.7]; age, 43 [11] years; 72 [80%] female). The eTRE+ER group adhered 6.0 (0.8) days per week. The eTRE+ER intervention was more effective for losing weight (-2.3 kg; 95% CI, -3.7 to -0.9 kg; P = .002) but did not affect body fat (-1.4 kg; 95% CI, -2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (-4.2%; 95% CI, -14.9 to 6.5%; P = .43). The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d. The eTRE+ER intervention also improved diastolic blood pressure (-4 mm Hg; 95% CI, -8 to 0 mm Hg; P = .04) and mood disturbances, including fatigue-inertia, vigor-activity, and depression-dejection. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups. In a secondary analysis of 59 completers, eTRE+ER was also more effective for losing body fat and trunk fat than CON+ER. Conclusions and relevance: In this randomized clinical trial, eTRE was more effective for losing weight and improving diastolic blood pressure and mood than eating over a window of 12 or more hours at 14 weeks. Trial registration: ClinicalTrials.gov Identifier: NCT03459703.
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Peripheral clocks are known to modulate circadian patterns of insulin secretion. Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by the intestinal L-cell that acts as a link between the gut and pancreatic β-cell. Herein, we demonstrate the existence of a diurnal rhythm in GLP-1 secretory responses to an oral glucose load in rats, with increased release immediately preceding the normal feeding period. This profile of GLP-1 release correlated with the pattern in insulin secretion, and both rhythms were completely inverted in animals subjected to a 12-hr feeding cycle disruption and abolished in rats maintained under constant light conditions. A daily variation in the insulin response to exogenous GLP-1 was also found. Consistent with these in vivo findings, we demonstrated a circadian pattern in the GLP-1 secretory response to different secretagogues in murine GLUTag cells, as well as in the mRNA levels of several canonical clock genes. Furthermore, significant changes in the expression of several genes were demonstrated by microarray and knockdown of two of them, thyrotroph embryonic factor and protein tyrosine phosphatase 4a1, resulted in altered GLP-1 secretion. Collectively, these results indicate that an independent peripheral clock in the L-cell drives a circadian rhythm in GLP-1 secretory responses.
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Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle.
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Breakfast skipping is associated with obesity and an increased risk of type 2 diabetes. Later chronotypes, individuals who have a preference for later bed and wake times, often skip breakfast. The aim of the study was to explore the relationships among breakfast skipping, chronotype, and glycemic control in type 2 diabetes patients. We collected sleep timing and 24-h dietary recall from 194 non-shift-working type 2 diabetes patients who were being followed in outpatient clinics. Mid-sleep time on free days (MSF) was used as an indicator of chronotype. Hemoglobin A1C (HbA1C) values were obtained from medical records. Hierarchical linear regression analyses controlling for demographic, sleep, and dietary variables were computed to determine whether breakfast skipping was associated with HbA1C. Additional regression analyses were performed to test if this association was mediated by chronotype. There were 22 participants (11.3%) who self-reported missing breakfast. Breakfast skippers had significantly higher HbA1C levels, higher body mass indices (BMI), and later MSF than breakfast eaters. Breakfast skipping was significantly associated with higher HbA1C values (B = 0.108, p = 0.01), even after adjusting for age, sex, race, BMI, number of diabetes complications, insulin use, depressive symptoms, perceived sleep debt, and percentage of daily caloric intake at dinner. The relationship between breakfast skipping and HbA1C was partially mediated by chronotype. In summary, breakfast skipping is associated with a later chronotype. Later chronotype and breakfast skipping both contribute to poorer glycemic control, as indicated by higher HbA1C levels. Future studies are needed to confirm these findings and determine whether behavioral interventions targeting breakfast eating or sleep timing may improve glycemic control in patients with type 2 diabetes.
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Circadian rhythms are integral to the normal functioning of numerous physiological processes. Evidence from human and mouse studies suggests that loss of rhythm occurs in obesity and cardiovascular disease and may be a neglected contributor to pathophysiology. Obesity has been shown to impair the circadian clock mechanism in liver and adipose tissue but its effect on cardiovascular tissues is unknown. We investigated the effect of dietinduced obesity in C57BL6J mice upon rhythmic transcription of clock genes and diurnal variation in vascular and metabolic systems. In obesity clock gene function and physiological rhythms were preserved in the vasculature but clock gene transcription in metabolic tissues and rhythms of glucose tolerance and insulin sensitivity were blunted. The most pronounced attenuation of clock rhythm occurred in adipose tissue, where there was also impairment of clock-controlled master metabolic genes and both AMPK mRNA and protein. Across tissues, clock gene disruption was associated with local inflammation but diverged from impairment of insulin signalling. We conclude that vascular tissues are less sensitive to pathological disruption of diurnal rhythms during obesity than metabolic tissues and suggest that cellular disruption of clock gene rhythmicity may occur by mechanisms shared with inflammation but distinct from those leading to insulin resistance.
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Evaluation of the existence of a diurnal pattern of glucose tolerance after mixed meals is important to inform a closed-loop system of treatment for insulin requiring diabetes. We studied 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA(1c) (5.2 ± 0.0%) to determine such a pattern in nondiabetic individuals. Identical mixed meals were ingested during breakfast, lunch, or dinner at 0700, 1300, and 1900 h in randomized Latin square order on 3 consecutive days. Physical activity was the same on all days. Postprandial glucose turnover was measured using the triple tracer technique. Postprandial glucose excursion was significantly lower (P < 0.01) at breakfast than lunch and dinner. β-Cell responsivity to glucose and disposition index was higher (P < 0.01) at breakfast than lunch and dinner. Hepatic insulin extraction was lower (P < 0.01) at breakfast than dinner. Although meal glucose appearance did not differ between meals, suppression of endogenous glucose production tended to be lower (P < 0.01) and insulin sensitivity tended to be higher (P < 0.01) at breakfast than at lunch or dinner. Our results suggest a diurnal pattern to glucose tolerance in healthy humans, and if present in type 1 diabetes, it will need to be incorporated into artificial pancreas systems.
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Cardiovascular disease is a serious complication of diabetes mellitus. In the last 2 decades, great strides have been made in reducing microvascular complications in patients with diabetes through improving glycemic control. Decreasing rates of cardiovascular events have proved to be more difficult than simply intensifying the management of hyperglycemia. A tremendous effort has been made to deepen understanding of cardiovascular disease in diabetes and to formulate the best treatment approach. This review summarizes the current state of knowledge and discusses areas of uncertainty in the care of patients with diabetes who are at risk for cardiovascular disease.
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Our goal was to evaluate the effect of breakfast size and composition on body weight, glycemic control, and metabolic markers in adults with type 2 diabetes mellitus (T2DM). 59 overweight/obese adults with T2DM were randomized to one of two isocaloric diabetic diets for 3 months; big breakfast (BB), breakfast was rich in fat and protein and provided 33% of total daily energy or small breakfast (SB), breakfast was rich in carbohydrates and provided 12.5% of total daily energy. Although body weight was reduced similarly in both groups, the BB group showed greater HbA1c and systolic blood pressure reductions (HbA1c: -4.62% vs. -1.46%, p = 0.047; SBP -9.58 vs. -2.43 mmHg; p = 0.04). T2DM medication dose was reduced in a greater proportion of the BB participants (31% vs. 0%; p = 0.002) while in the SB, a greater proportion of participants had a dose increases (16.7% vs. 3.4%; p = 0.002). Hunger scores were lower in the BB group and greater improvements in fasting glucose were observed in the BB group. A simple dietary manipulation enriching breakfast with energy as protein and fat appears to confer metabolic benefits and might be a useful alternative for the management of T2DM.
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Glycaemic index testing is conducted in the morning, however postprandial glycaemia has a diurnal rhythm. The study aimed to evaluate the effect of glycaemic index on glucose tolerance at different times during the day. A randomised controlled crossover study was conducted in ten healthy participants after a standardised premeal and eight hour fast. Low (37) and high glycaemic index (73) meals, matched for energy, available carbohydrate, protein and fat, were consumed at 08:00 h and 20:00 h. Blood samples were taken for 2 h postprandially. Postprandial glucose area under curve showed effect with time of day after both meals (Low p < 0.001, High p = 0.003), and a trend (p = 0.06) to higher glycaemic responses in the evening for low glycaemic index meal. No differences were observed in insulin responses. Despite the calculated difference in meal glycaemic index little difference was observed in morning responses, but differences were seen in the evening when insulin insensitivity is increasing, the glycaemic response increase was proportionally greater for low glycaemic index meals. Low glycaemic index foods are of less value in glycaemic control in the evening than the morning. Consuming food late in the day has a detrimental metabolic impact irrespective of glycaemic index.
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Objective: Few studies examined the association between time-of-day of nutrient intake and the metabolic syndrome. Our goal was to compare a weight loss diet with high caloric intake during breakfast to an isocaloric diet with high caloric intake at dinner. Design and methods: Overweight and obese women (BMI 32.4 ± 1.8 kg/m(2) ) with metabolic syndrome were randomized into two isocaloric (~1400 kcal) weight loss groups, a breakfast (BF) (700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) or a dinner (D) group (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner) for 12 weeks. Results: The BF group showed greater weight loss and waist circumference reduction. Although fasting glucose, insulin, and ghrelin were reduced in both groups, fasting glucose, insulin, and HOMA-IR decreased significantly to a greater extent in the BF group. Mean triglyceride levels decreased by 33.6% in the BF group, but increased by 14.6% in the D group. Oral glucose tolerance test led to a greater decrease of glucose and insulin in the BF group. In response to meal challenges, the overall daily glucose, insulin, ghrelin, and mean hunger scores were significantly lower, whereas mean satiety scores were significantly higher in the BF group. Conclusions: High-calorie breakfast with reduced intake at dinner is beneficial and might be a useful alternative for the management of obesity and metabolic syndrome.