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OMICS International
Journal of Diabetes & Metabolism
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ISSN: 2155-6156
Ohlsson et al., J Diabetes Metab 2017, 8:3
DOI: 10.4172/2155-6156.1000733
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
Research Article
Abstract
Background: Satiety and sweet craving are strongly inuenced by secretion of gastrointestinal hormones,
which are dependent on dietary factors. An Okinawan-based Nordic breakfast with moderately low carbohydrate
content and high fat and protein contents has shown increased postprandial satiety, along with improved endocrine
and metabolic prole. The primary aim of the study was to estimate the degree of satiety, sweet cravings, and
gastrointestinal symptoms, during and after dietary intervention, and to correlate these subjective estimates with
anthropometric, metabolic, and hormonal parameters and health-related quality of life (HRQoL). Secondary aim was
to correlate the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) against the HRQoL questionnaire
RAND-36.
Methods: Thirty type 2 diabetes patients were given the Okinawan-based Nordic diet during 12 weeks. Blood
sampling, anthropometric measuring and completion of questionnaires about satiety and sweet cravings, VAS-IBS,
and RAND-36 were performed at baseline, after 12 weeks of dietary intervention, and after 16 weeks of follow-up.
Results: The satiety was increased after dietary intervention, and sweet craving was decreased, without
correlations with any parameters. These changes persisted throughout the study period (p=0.002). At follow-up,
satiety was inversely correlated with GIP (p=0.041) and Social Functioning (p=0.044). Sweet craving correlated with
leptin levels (p=0.037), weight (p=0.048), BMI (p=0.001), waist circumference (p=0.006), vitality (p=0.046), and less
abdominal pain (p=0.034). Psychological improvement was seen during the dietary intervention, and gastrointestinal
symptom reduction afterwards, with correlations between the parameters.
Conclusions: A diet with moderately low carbohydrate content and high ber, fat, and protein contents
renders an increased satiety and a reduced sweet craving, independently of anthropometric, hormonal, metabolic
or psychological factors. Improved psychological well-being and HRQoL preceeds the reports of decreased
gastrointestinal symptoms.
High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently
of Anthropometric Hormonal and Metabolic Factors
Bodil Ohlsson1*, Gassan Darwiche1, Bodil Roth1, Mariette Bengtsson2 and Peter Hoglund3
1Department of Internal Medicine, Skane University Hospital, Lund University, Malmo, Sweden
2Department of Care Science, Malmo University, Sweden
3Department of Clinical Chemistry & Pharmacology, Skane University Hospital, Lund University, Lund, Sweden
*Corresponding author: Bodil Ohlsson, Department of Clinical Sciences, Skane
University Hospital, Inga Marie Nilsson Street 32, S-205 02 Malmo, Sweden, Tel:
+4640331000; Fax: +4640336208; E-mail: bodil.ohlsson@med.lu.se
Received February 24, 2017; Accepted March 20, 2017; Published March 27,
2017
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High
Fiber Fat and Protein Contents Lead to Increased Satiety Reduced Sweet Cravings
and Decreased Gastrointestinal Symptoms Independently of Anthropometric
Hormonal and Metabolic Factors. J Diabetes Metab 8: 733. doi: 10.4172/2155-
6156.1000733
Copyright: © 2017 Ohlsson B, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Keywords: Gastrointestinal hormones; Gastrointestinal symptoms;
Health-related quality of life (HRQoL); Okinawan-based Nordic diet;
Satiety; Sweet craving
Introduction
Several gastrointestinal hormones are involved in the regulation
of appetite control, digestion, and satiety, e.g., cholecystokinin
(CCK), ghrelin, glucagon-like peptide-1 (GLP-1), glucose-dependent
insulinotropic polypeptide (GIP), insulin, leptin, and polypeptide YY
(PYY) [1,2]. Both diet and physical activity have great impact on the
hormonal secretion [3,4] and perception of gastrointestinal complaints
and quality of life [5]. High protein content in the diet stimulate satiety
through several hormones and vagal aerent pathways, and protein has
been described as the most potent satiating macronutrient [6]. Also
a high fat content stimulates hormone secretion with ensuing slower
gastric emptying, which is an important factor for experience of satiety
[7,8]. During the last years, patients with functional bowel diseases
are recommended to avoid food components with high intake of
carbohydrates, to reduce their gastrointestinal complaints [9]. Not only
the food content, but also irregularity of food intake may be important
for perception of gastrointestinal complaints [5,10].
A modied Okinawan diet has been developed consisting of
moderately low carbohydrate content, and higher contents of ber,
fat, and protein, with tastes and food components suitable for the
Nordic population [11]. e diet induced weight reduction, lowered
blood pressure, and improvement of metabolic parameters in type 2
diabetes. At the same time, an improvement of health-related quality
of life (HRQoL) was observed [11]. Already a single breakfast of the
diet rendered improved metabolic parameters with increased satiety
compared with a traditional breakfast [12]. In contrast, serum zonulin,
a biomarker of increased intestinal permeability [13], was increased
during the dietary intervention [14].
Our hypothesis was that this diet inuences the sensation of satiety,
sweet cravings, and gastrointestinal symptoms through its eects on
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 2 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
hormonal and metabolic parameters. Blood samples were taken before
study start, aer 12 weeks of dietary intervention, and aer 28 weeks
when the participants had chosen their own food for 16 weeks. At the
same time, the patients had to estimate their satiety, sweet cravings, and
gastrointestinal symptoms on visual analog scales (VAS), and HRQoL
on RAND-36. e result on anthropometric and metabolic parameters
and RAND-36 are presented in a previous report [11]. e objective of
the present study was to estimate the degree of satiety, sweet cravings,
and gastrointestinal symptoms during and aer a dietary intervention,
and to correlate these subjective estimates with anthropometric and
metabolic parameters and plasma levels of hormones regulating satiety
and well-being, i.e., CCK, cortisol, C-peptide, ghrelin, glucagon, GLP-
1, GIP, insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), PYY,
resistin, and visfatin, and HRQoL.
Subjects and Methods
e subjects were treated according to the Helsinki declaration
and the study was approved by the Regional Ethics Review Board at
Lund University (2014/460). All subjects were informed written and
orally, and gave their written, informed consent before entering the
study which was monitored by an external monitor and registered at
ClinicalTrials.gov data base (NCT02405806).
Study population
Patients with type 2 diabetes, aged between 18-70 years, were
recruited at a primary health care center in the southernmost district
of Sweden. Patients were to have both parents inborn in Scandinavia,
to avoid possible inuence of ethnicity on the study results. ey were
included in the study independently of body mass index (BMI) or anti-
diabetic treatment regimen. Overall exclusion criteria were severe food
allergy, and severe heart, pulmonary, cardiovascular, malignant, or
psychiatric diseases. Patients with type 1 diabetes mellitus, severe liver
insuciency, dened as spontaneous international normalized ratio
(INR)>1.1, or severe renal insuciency, dened as glomerular ltration
rate (GFR)<30 mL/min/1.73 m2, as well as patients with a prior major
gastrointestinal surgery were excluded. Patients with known alcohol
and drug abuse were not considered for inclusion. Participants were
initially informed of the project design and purpose through a letter
sent by mail. One week later, all patients were contacted by phone by
one of three investigators (BO, GD, physicians, or EL, nutritionist).
Study design
e trial was a clinical prospective interventional study and
conducted at Skane University Hospital, Malmo, Sweden, during 12
weeks with a new modied diet, followed by a clinical follow-up aer
another 16 weeks with unrestricted diets. Food for preparation of
lunch and dinner was delivered in a cooler bag home to the subjects
three times a week free of charge, along with written information and
recipes for meal preparation. Each participant had to prepare their own
breakfast. e participants were encouraged to maintain their regular
physical activity habits throughout the intervention.e study data
consisting of blood sampling; assessments of anthropometric data; and
completion of questionnaires was obtained at 3 separate visits: 1) at
study start before introduction of the modied diet; 2) aer 12 weeks
on the modied diet; and 3) aer 16 weeks on unrestricted diet (Figure
1). Blood samples were collected through an intravenous catheter aer
a 10-h fast. Plasma and serum was harvested and stored at -80°C until
analyzed for metabolic parameters and hormonal concentrations.
e physician and the patient had a discussion about the compliance
and ability to follow the dietary recommendations and the degree of
satisfaction with the food composition. A clinical examination including
measuring of anthropometric data was accomplished. To estimate the
degree of satiety and sweet hunger, a scoring on a visual analogue scale
(VAS) was used. To estimate the degree of abdominal symptoms and
HRQoL, the Visual Analog Scale for Irritable Bowel Syndrome (VAS-
IBS) and RAND-36 were lled in. e data surveys were completed at
home one day before the hospital visit. e study started on 2 February
2015 and ended on 18 September 2015.
Diets
e diet is based on the traditional Okinawan diet [15,16] but
modied to suit the Nordic diet with tastes and food components
suitable for the Nordic population [11]. e meal composition is
consistent with moderately low carbohydrate content [17]. At the same
time, the contents of ber, fat, and protein are increased, which lead
to a bigger meal demanding more mastication and prolonged meal
intake [12]. e food is based on traditional Nordic raws, e.g., whole
grains, vegetables, legumes, root crops, fat sh, birds, fruits, berries,
and nuts, with minimal industrial processing. At the same time, the
amount of sugar, red meat, processed meat, and dairy products is
limited. e diet has a good nutritional supply including a mean calorie
intake around 1900 kcal/day, which is slightly lower compared with a
traditional diet. e participants were allowed to eat three meals a day
including breakfast, lunch, and dinner, and two snacks between meals
consisting of a variety of fruits, berries, and seeds. Organic food items
were preferred whenever possible. At the occurrence of cravings, the
subjects were instructed to eat a third snack (e.g., carrots, boiled eggs,
mackerel in tomato sauce, or cottage cheese with berries) to avoid eating
fast carbohydrates. Raw vegetables or green salad were to be ingested
with the main meals; 100 gram at breakfast and 150 gram at lunch and
dinner, respectively. e participants were instructed always to start
with the vegetables and to eat slowly. Nutrition information is given
in Table 1.
Two breakfast alternatives were ingested, depending on their
ordinary breakfast ingested, and the participants bought and prepared
the meals on their own. e other meals were planned together with the
kitchen of Igelosa Life Science Lab (Lund University) and delivered to
the subjects free of charge, along with recipes and instructions on how
to cook the food.
No dietary supplements such as sh oil, probiotics or multivitamin
drugs were allowed to be introduced during the study period. As most
one visit to a restaurant or to another diet per week was allowed.
Journeys or a stay during a longer time period at another place had to
be discussed with the investigators (BO and GD). Maximal intake of
alcoholic beverages was set to 30 g ethanol/week (2.5 glasses wine).
Assessment of clinical variables and anthropometry
e investigation took place under identical conditions by two
clinically experienced physicians (BO and GD). Physical examination
included cardiopulmonary, abdominal, and neurological examinations
as well as measurements of blood pressure, pulse, respiratory rate,
weight, height, waist circumference, and assessment of BMI. A protocol
was completed including data on presence of diabetic complications;
information whether they already were on ongoing weight-reducing
diet; intake of dietary supplements, vitamins, and probiotics; changes
in medication; physical activity or routines; as well as any extraordinary
events of daily life.
Blood sampling and chemistry analyses
All samples consisted of whole blood drained into
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 3 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
ethylenediaminetetra-acetic acid (EDTA) glass tubes (BD Microtainer,
New Jersey, USA) or serum separation tubes (SST) with coagulation
activator and gel (BD Microtainer). Blood was centrifuged at 3000 rcf
for 5 min and plasma and serum was stored in -80°C until analyzed.
Cortisol, C-peptide, and insulin in serum and plasma glucose and blood
hemoglobin A1c (HbA1c) were analyzed by standard methods in the
Department of Clinical Chemistry. Zonulin was measured in serum
and feces according to the manufacturer´s instructions, previously
described [14].
Hormonal analyses
e Luminex analyses were performed within 9 months. Human
diabetes 10-plex panel (Bio-Plex Pro™ Human Diabetes Immunoassay
control no 5029560-1 and 5040782, Bio-Rad Laboratories, CA, USA)
was performed on the Luminex-200 (Luminex xMAP, Bio-Rad
Laboratories) and data were analyzed using Bio-Plex Manager soware
6.0 (Bio-Rad Laboratories). Hormones (pg/ml) measured were ghrelin,
glucagon, GLP-1, GIP, leptin, PAI-1, resistin, and visfatin. For more
details about the analyses, see Ohlsson et al. [12]. CCK and PYY were
analyzed by ELISA according to the manufacturer´s instruction (Cloud-
Clone Corp. Houston, USA, CEB802 Hu and CEB067 Hu, respectively).
Questionnaires
Satiety and sweet cravings
e patients completed one VAS for satiety and one VAS for sweet
cravings at 12 weeks and at 28 weeks aer study start, according to
previous validation [18]. ese items were measured on a scale from
0-100, where 0 represents no satiety or no sweet cravings, respectively,
and 100 represents a maximal feeling of satiety or maximal feeling of
Figure 1: Flow-chart of patient recruitment and study design. VAS-IBS=Visual Analog Scale for Irritable Bowel Syndrome. Two patients interrupted the
study at 6 weeks on diet, and data collected at that time point was calculated together with data from patients with 12 weeks of intervention.
Nutritional value Unit Calculated value E% Recommended (NNR 2012)
Total Energy kcal 1866
Energy (excluding beverages) kcal 1629
Protein g95.0 23 10-20 E%
Fat g63.9 35 25-40 E%
Saturated fatty acids g18.7 10 <10 E%
Polyunsaturated fatty acids g14.9 8 5-10 E%
Mono-unsaturated fatty acids g17.8 10 10-20 E%
Carbohydrate g168.4 42 45-60 E%
Sucrose g23.5 6 <10 E%
Dietary bre g35.9 25-35 g
Nordic Nutrition Recommendations (NNR) 2012 are shown in ref No 15
Table 1: Nutrition composition and daily mean intake of energy, nutrients, and food components of the modied Okinawan-based Nordic diet,
compared with Nordic Nutrition Recommendations (NNR) 2012.
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 4 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
for disappearance. Two patients interrupted the study at 6 weeks on
diet, which time point was considered as end of the intervention, and
data collected at that time point was calculated together with data from
patients with 12 weeks of intervention.
We tested the hypotheses with linear mixed eect models to
analyze continuous variables, with random intercept and unstructured
covariance’s for repeated measures within a patient, with visits as
nominal xed eect, using baseline as reference. We assumed that
missing observations were unrelated to the observed value, i.e., missing
at random. In these analyses predicted mean values and their 95%
condence limits are presented, together with estimates of changes
from baseline and 95% condence limits and p-values for the changes.
Fisher´s exact test was used for dichotomous variables and Spearman´s
correlation test for correlation of continuous variables. Mann-Whitney
U test was used for comparisons of VAS scales for satiety and sweet
craving and values are presented as median and interquartile ranges.
Descriptive statistics are presented as means and standard deviations
(SD) for continuous variables and as counts or frequencies for
categorical variables. Statistics were done using MATLAB R2015a
(Mathworks Inc.) or IBM SPSS Statistics 23 (Statistical Package for the
Social Sciences). P<0.05 was considered statistically signicant.
Results
Basal characteristics
In total, 45 patients were randomly selected aer consideration of
inclusion and exclusion criteria. Of these, 30 patients (17 women), mean
age 57.5 ± 8.2 years, were included from 45 invited patients (Figure 1).
Reasons for not inclusion were: unwillingness to participate (n=11), late
autoimmune diabetes in adult (LADA) (n=1), a history of gastric by-
pass surgery (n=1), pregnancy (n=1), or already on a diet (n=1).
e duration of type 2 disease was 10.4 ± 7.6 years. e treatment
given was metformin (40%), metformin in combination with
insulin (27%), insulin solely (13%), metformin in combination with
sulfonylurea (7%), diet solely (7%), sulfonylurea (3%), or dipeptidyl
peptidase-4 (DPP) (3%). e most common secondary complication to
the disease was autonomic neuropathy and/or peripheral neuropathy
(30%), retinopathy (27%), and nephropathy and macroangiopathy
(17% in both). Only one patient had a veried gastroparesis.
Sixteen percent had only completed primary school, 57% had
completed high school, and 27% had higher education. e majority
was employed, 67%, whereas 17% were retired. e rest of the patients
were on sick leave or unemployed. Twenty of the patients were married
or cohabitant, whereas six were divorced or widow/widower and four
were living alone. Smoking and snung or both occurred in 23% of the
patients.
An alcoholic beverage was ingested by half of the patients once a
month or less, by 27% for 2-4 times a month, by 13% for 2-3 times a
week, and 0% were teetotalers. A moderate physical exercise during
leisure time was most common (53%), followed by moderately regular
exercise (27%), regular exercise and training (13%), and sedentary
leisure time (7%). Antihypertensive medication was prescribed in 63%
of patients and lipid-lowering medication in 47%.
Only 2 patients had sole dietary treatment of the diabetes. In 15
subjects, the anti-diabetes medication was gradually reduced during
dietary intervention, and two subjects, one with both oral hypoglycemic
agents and insulin, had their medication cancelled. Of the other 12
subjects with insulin treatment, three had their insulin therapy cancelled
sweet cravings, respectively. At 12 and 28 weeks aer study start, the
patients also had to answer the questions: “Can you imagine to continue
with this kind of food regime?”, “How strong is your satiety today
compared with the feeling of satiety at study start and at dietary stop
aer 12 weeks, respectively?”, and “How strong is your sweet hunger
today compared with the feeling of sweet hunger at study start and
at dietary stop aer 12 weeks, respectively?”. e questions had to be
answered to the same degree, less, or more.
Visual analog scale for irritable bowel syndrome
e VAS-IBS was used to investigate gastrointestinal complaints in
the study groups before study start, and at 12 and 28 weeks aerwards.
VAS-IBS is a validated self-rating questionnaire for estimation of
the most common gastrointestinal complaints in patients with non-
organic, functional bowel disease experienced during the last 2 weeks
[19]. is questionnaire has also been validated for estimation of
symptoms over time [20]. e seven items measured in the VAS-IBS
address the symptoms abdominal pain, diarrhea, constipation, bloating
and atulence, nausea and vomiting, psychological well-being, and
intestinal symptoms´ inuence on daily life. ese items were measured
on a scale from 0-100, where 0 represents severe problems and 100
represents a complete lack of problems. An additional two questions,
if the subject experienced urgency to defecation and had a sensation of
incomplete evacuation, were answered with yes or no.
Health-related quality of life questionnaire (RAND-36)
HRQoL refers to how health impacts on a person´s ability to function
in daily life, and the persons perceived well-being in physical, mental
and social domains of life [21]. e widely used and well-validated
self-report questionnaire RAND 36-Item Health Survey was applied to
evaluate HRQoL in present study. is questionnaire has been used
to measure HRQoL in many various diseases, and normal references
values are available [22]. Rand 36-items comprises eight health concepts
with multi-item scales (35 items): Physical Functioning (PF) (10 items);
Role function limitations caused by Emotional problems (RE) (3 items);
Role function limitations caused by Physical health problems (RP)
(4 items); General Health (GH) (5 items); Social Functioning (SF) (2
items); Mental Health based on emotional well-being (MH) (5 items);
Vitality related to energy and fatigue (VT) (4 items); and Bodily Pain
(BP) (2 items). An additional single item assesses change in perceived
health during the last 12 months. ese parameters are valuable to
estimate the eects evoked in daily life, by a change in life style factors.
e few minor dierences between SF-36 and RAND-36 have been
described by Hays et al. [23].
Statistical methods
Two hypotheses were raised: 1) a diet with low carbohydrate content
and high fat and protein contents renders higher satiety and lower sweet
cravings and aects gastrointestinal symptoms and 2) the regulation of
satiety, sweet cravings, and gastrointestinal symptoms are aected by
anthropometric, hormonal, and metabolic factors and HRQoL.
A power analysis was performed based on a previous unpublished
pilot study, and we determined that nine subjects was required to
demonstrate clinically signicant dierences in metabolic parameters
with 80% power at 5% signicance level. We expected that diastolic
blood pressure was the variable demanding most subjects to be able
to discover, and that we needed 18 persons to demonstrate clinically
signicant dierences in diastolic pressure with 80% power at 5%
signicance level. We planned to recruit 25-35 persons to compensate
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 5 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
the dietary intervention, and the decrease remained aer 28 weeks,
as also was true for fasting glucose and HbA1c (Table 5). e fasting
levels of CCK (mean change=-7 pg/ml, p=0.005), cortisol (mean
change=-41 pg/ml, p=0.015), C-peptide (mean change=-0.11 pg/
ml, p=0.022), glucagon (mean change=-0.66 pg/ml, p=0.003), GLP-
1 (mean change=-0.88 pg/ml, p=0.013), GIP (mean change=-23 pg/
ml, p<0.001), insulin (mean change=-6.43 pg/ml, p=0.004), leptin
(mean change=-3554 pg/ml, p<0.001), and PYY (mean change=-427
pg/ml, p<0.001) were decreased at week 12 compared with baseline,
and aer 28 weeks, ghrelin (mean change=-123 pg/ml, p=0.012), PYY
(mean change=-264 pg/ml, p=0.002), and visfatin (mean change=-186,
p=0.021) was lowered, compared with baseline. Serum zonulin
increased during the dietary intervention, and the increased zonulin
levels persisted throughout the follow-up. Feces zonulin increased
during the dietary intervention, but returned to basal levels when the
intervention was stopped (Table 5).
Correlations between satiety, sweet cravings, gastrointestinal
symptoms, and anthropometric, hormonal, and metabolic
parameters, and HRQoL
Satiety or sweet cravings did not correlate with any parameters aer
the dietary intervention. At follow-up, satiety correlated inversely with
GIP (rs=-0.450, p=0.041) and Social Functioning (rs=-0.433, p=0.044).
At the same time, sweet cravings correlated with leptin (rs=0.458,
p=0.037), weight (rs=0.426, p=0.048), BMI (rs=0.651, p=0.001), and
waist circumference (rs=0.565, p=0.006). Furthermore, sweet cravings
also correlated with vitality (rs=0.430, p=0.046) and less abdominal
pain (rs=0.453, p=0.034). No other anthropometric parameters, nor
fasting levels of hormonal or metabolic parameters correlated to the
overall sensations of satiety and sweet cravings measured in VAS scales
(data not shown).
e only anthropometric, hormonal or metabolic correlation
with any VAS-IBS scale at baseline was the correlation between less
symptoms of bloating and atulence and BMI (rs=0.463, p=0.009) and
C-peptide (rs=0.405, p=0.026), and between less constipation and BMI
(rs=0.490, P=0.006). e improvements of anthropometric, hormonal
or metabolic parameters during dietary intervention or at follow-up
were not reected by a corresponding improvements in symptoms or
psychologic well-being (data not shown). e only correlation between
zonulin and gastrointestinal symptoms was a weak inverse correlation
between feces zonulin and nausea and vomiting at follow-up (rs=-
0.445, p=0.033), indicating higher feces zonulin levels in patients with
more nausea and vomiting.
e improvements in HRQoL preceded the improvements in
gastrointestinal symptoms (Tables 3 and 4). Psychological well-being
estimated by VAS-IBS correlated with Social Functioning and Mental
Health (Table 6). ere was no correlation between the participants
scoring in VAS-IBS of abdominal pain and Bodily Pain in RAND-36
(rs=0.275, p=0.141). However, there were correlations between their
and another eight had their insulin doses reduced.
Compliance and satisfaction
When answering the question about more, less or the same
degree of satiety or sweet cravings at week 12, the majority of patients
experienced more satiety (60%) and less sweet cravings (83%) compared
with prior study start. e majority of patients at week 28, experienced
the same degree of satiety and sweet cravings as at week 12. e dietary
inuence on sweet cravings was greater than on satiety (Table 2).
When scoring the overall degree of satiety on a VAS scale, the
patients scored their satiety to 75 (67-82) at week 12 and to 69 (60-78)
at week 28 (p=0.264). e overall sweet cravings was scored to 29 (21-
38) and 41 (31-52) at the two time points, respectively, with a tendency
of increased sweet cravings at week 28 (p=0.06).
Prior study start, most of the participants had irregular food habits.
One of the major changes during the study was thus to keep regular
meals. At the follow-up aer 28 weeks, only 2-3 patients out of 23 were
prepared to completely change their life style and fully adhere to the
dietary regime for the future. Almost all of the participants wanted
to mainly adhere to the dietary regime. Compared with previous
study start, the majority had: 1) kept the breakfast recommended; 2)
continued with more fruits and vegetables as snacks instead of cakes;
and 3) tried to keep regular meals. ose who adhered to this regime
had not regained the weight reduction (individual data not shown).
Gastrointestinal symptoms
At week 12, the mean scores for the VASs improved and were
signicantly better for diarrhea (p=0.022), bloating and atulence
(p=0.025), and psychological well-being (p=0.001) compared with
baseline. At week 28, the mean scores for abdominal pain (p=0.049)
and nausea and vomiting (p=0.028) were signicantly better compared
with baseline, and there were further improvements in the mean scores
for diarrhea (p=0.002) and bloating and atulence (p=0.003). e
largest improvement during the study was observed in the bloating and
atulence scale (Table 3).
Health-related quality of life
At week 12, the mean scores for the RAND-36 scale improved and
were signicantly higher for Physical Functioning (p<0.001), General
Health (p<0.001), Vitality (p=0.011), Social Functioning (p=0.001),
and Mental Health (p=0.003) aer dietary intervention. e increase
in the Vitality scale peaked at week 28 (p<0.001). Even though the
other scale scores had declined at this point, the mean increase in
Physical Functioning, General Health, and Social Functioning were
still signicantly improved relative to baseline (Table 4).
Anthropometric, hormonal and metabolic changes
Weight, BMI and waist circumference were decreased during
Satiety P- value Sweet cravings P-value
Same More Less Same More Less
Week 12 (n=30)
Vs. baseline 8 (27) 18 (60) 4 (13) 1 (3) 4 (13) 25 (83)
Week 28 (n=23)
Vs. baseline 13 (57) 8 (35) 2 (9) 8 (35) 1 (4) 14 (61)
Vs. week 12 17 (74) 3 (13) 3 (10) 0.239 16 (70) 4 (17) 3 (13) 0.002
The experience of satiety and sweet cravings at week 12 and week 28 in comparison with baseline and week 12 after 3 months of dietary intervention. N=30 at study start.
Values are presented as number and percentage. Fisher´s exact test. P<0.05 was considered statistically signicant.
Table 2: Satiety and sweet cravings.
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 6 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
Variable Mean 95% CI Lower Higher Mean change 95% CI Lower Higher P-value
Pain
Baseline 82.9 76.5 89.3
Week 12 88.2 81.4 95.0 5.3 -0.7 11.3 0.081
Week 28 89.3 82.2 96.3 6.4 0.0 12.7 0.049
Diarrhea
Baseline 80.0 73.2 86.7
Week 12 87.8 80.3 95.2 7.8 1.1 14.5 0.022
Week 28 90.6 83.2 97.9 10.6 4.1 17.1 0.002
Constipation
Baseline 87.1 81.4 92.9
Week 12 84.1 75.8 92.4 -3.0 -10.7 4.7 0.442
Week 28 87.9 81.4 94.5 0.8 -5.1 6.7 0.785
Bloating and atulence
Baseline 70.7 61.9 79.6
Week 12 80.2 69.2 91.3 9.5 1.2 17.8 0.025
Week 28 82.3 71.8 92.8 11.6 4.0 19.1 0.003
Nausea and vomiting
Baseline 93.3 89.8 96.9
Week 12 94.8 90.7 98.8 1.4 -1.0 3.9 0.248
Week 28 96.0 92.0 100.3 2.7 0.3 5.1 0.028
Psychological well-being
Baseline 76.6 69.9 83.3
Week 12 86.6 79.8 93.4 10.0 4.0 16.0 0.001
Week 28 84.1 75.6 92.6 7.5 -0.5 15.4 0.064
Inuence on daily life
Baseline 80.6 72.0 89.2
Week 12 82.5 7.8 92.3 1.9 -6.9 10.8 0.664
Week 28 86.7 77.4 96.1 6.1 -2.2 14.5 0.149
The mean values and mean changes are given for pain, diarrhea, constipation, bloating, nausea, psychological well-being and intestinal symptoms inuence on daily life at
inclusion (baseline), 12 weeks after diet intervention, and 12 weeks after the end of diet intervention (week 28). These items were measured on a scale from 0-100, where
0 represents severe problems and 100 represents a complete lack of problems. The 95% condence interval with higher and lower limits are shown. Linear mixed model.
P-value<0.05 was considered statistically signicant.
Table 3: Visual analog scale for irritable bowel syndrome (VAS) for evaluation of gastrointestinal symptoms.
scoring of abdominal pain in VAS-IBS and Vitality (rs=0.476, p=0.008)
and General Health (rs= 0.401, p=0.028) in RAND-36. Also the scoring
for the items diarrhea (rs=0.412, p=0.024), and the patients perceived
bowel symptoms inuence on daily life (rs=0.418, p=0.021) in VAS-
IBS, correlated to Vitality in RAND-36 (Table 6).
Discussion
In compliance with the present study results, we accepted the
research hypotheses that a dietary modication may increase the satiety
and reduce sweet cravings. Gastrointestinal symptoms correlated
with psychological well-being and HRQoL, but the improvement in
psychological parameters preceded improvement in gastrointestinal
symptoms. On the other hand, we rejected the research hypothesis
that changes in satiety, sweet cravings, and gastrointestinal symptoms
correlated with changes in anthropometric, hormonal, and metabolic
variables.
Aer an acute weight loss, the body react with increased appetite
to regain weight, reecting a continuing role for the gut-brain axis in
regulation of food intake and maintenance of body weight [24]. It is
therefore astonishing that satiety levels remained the same or stronger
during the trial, when the subjects ingested a lower calorie intake than
usual and lost in weight. Surprisingly, there was no correlation between
feeling of satiety or sweet cravings in the present study and any appetite-
regulating hormones such as CCK, ghrelin, GLP-1, insulin, leptin, and
PYY (1, 2, 3, 4), indicating other underlying possible mechanisms of
satiety. is is in line with that increased postprandial satiety aer a
single Okinawan-based breakfast did not either correlates with any
hormone levels [12].
e gastric volume is strongly correlated to the feeling of hunger
and satiation since it is the degree of gastric distention which is the
major determinant of satiation and satiety [7]. e Okinawan-
based Nordic diet contained a great amount of bers in the form of
vegetables, legumes, and whole-grain products. is means greater
food volume and increased gastric distention, which may explain the
increased satiety in absence of elevated hormonal levels. Furthermore,
the ber-rich diet demands more chewing and constitutes a slower
eating pattern with increased mastication. e sight of a greater food
volume and mastication stimulate the cephalic phase responses [25].
Mastication also has a direct eect on satiety through histamine
activation of para-ventricular nucleus and ventromedial hypothalamus
[26]. Experimental trials in healthy volunteers have shown that food
intake with increased mastication induces less feeling of hunger and
desire to eat [27], and slower eating leads to increased satiety scoring
[28]. In analogy, epidemiological studies show that fast eating is
associated with increased BMI and insulin resistance [29,30].
e rate of gastric emptying is a further major determinant of
postprandial satiety [7]. e delivery of luminal content to the intestine
stimulate gut hormone secretion and these hormones stimulate directly
at the level of the hypothalamic arcuate nucleus, or indirectly through
aerent vagal neurons, at the area of postrema and the nucleus tractus
solitaries [7]. ere is a relatively high inter-individual variation in the
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 7 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
rate of gastric emptying, whereas the intra-individual variation is low
when subjects are eating the same diet [31]. Several studies indicate that
the addition of viscous soluble bers to the meal [32], as well as bers
naturally present in food [33], reduces the gastric emptying rate and
the glycemic response to a test meal. Delayed gastric emptying leads
to a sustained gastric distention and a prolonged exposure of nutrients
and energy to the intestinal lumen [7].
High protein intake induce the production of anorexigenic gut
hormones, amino acids, and metabolites, which activates the arcuate
nucleus and nucleus tracts solitaries in the brain, resulting in satiety,
reduced food intake, and delayed gastric emptying [6]. Consequently,
high protein intake oen leads to weight reduction [6]. However, fat
content, and not protein content, is the major determinant of gastric
emptying rate [8,34]. e amount of energy intake was reduced aer
both lipid and protein intake. Furthermore, the eating-inhibitory eect
of lipid was most likely mediated by gastrointestinal hormones and
mechanisms, whereas other factors than gut hormones mediated the
eects of protein [3,8]. e gastric emptying rate was not measured
in the present study. Nevertheless, the food contained more bers and
greater volume than traditional food, as well as more fat and more
protein, which most likely resulted in a delay in gastric emptying
and activation of hypothalamic structures, and consequently, also an
increased satiety.
In experimental trials, prior exposure to sucrose solutions increase
sucrose preference by a positive feedback cycle [35]. Enteroendocrine
cells in the gut harbor sweet taste receptors which are implicated in
sweet taste preference. Several appetite regulatory peptides modulate
taste sensitivity through these receptors [36]. e Okinawan-based
Nordic diet contained almost no refrained sugar. Since dierent
carbohydrate sources aect the central reward systems dierently, the
food composition could explain the development of less cravings for
sweets [36], which was seen independently of the hormone prole.
e concomitant increase of satiety along with less hunger for sweets,
may eciently contribute to sustained, lowered body weight. e sweet
cravings was reduced during introduction of the diet, and this reduction
persisted aerwards. Although the participants did not fully adhere
to the new recommendations, most of them had kept regular meals,
a healthy breakfast, and a great daily intake of fruits and vegetables.
ese simple habits seem to be of importance to maintain satiation and
a low sweet cravings.
Since VAS-IBS and RAND-36 have dierent focus and the
questions are not equivalent, it is not possible to validate VAS-IBS
against RAND-36. However, it is possible to correlate the questions.
ere were correlations between the participants´scoring of their
symptoms in VAS-IBS and HRQoL in RAND-36 in some points, which
shows that physical and psychological factors inuence vitality, general
well-being, and daily life. is is also described in the literature for
Variable Mean 95% CI Lower Higher P-value
Physical Functioning
Baseline 75.7 69.3 82.1
Week 12 86.5 80.1 92.9 <0.001
Week 28 85.3 78.4 92.2 0.004
Physical Role Functioning
Baseline 74.2 60.7 87.6
Week 12 78.3 64.9 91.8 0.555
Week 28 73.3 57.7 88.8 0.911
Bodily Pain
Baseline 72.8 62.9 82.8
Week 12 79.7 69.1 90.3 0.109
Week 28 80.3 69.1 91.5 0.112
General Health
Baseline 58.7 51.2 66.1
Week 12 68.7 60.4 76.9 <0.001
Week 28 67.7 58.9 76.5 0.007
Vitality
Baseline 56.2 48.1 64.3
Week 12 66.7 56.2 77.1 0.011
Week 28 68.4 59.3 77.5 <0.001
Social Functioning
Baseline 78.4 70.6 86.3
Week 12 89.3 79.8 98.8 0.001
Week 28 87.4 77.4 97.3 0.015
Emotional Role Functioning
Baseline 81.1 71.3 90.9
Week 12 84.5 71.6 97.3 0.592
Week 28 83.8 69.7 97.8 0.699
Mental Health
Baseline 73.2 67.0 79.4
Week 12 82.0 75.3 88.7 0.003
Week 28 78.6 71.8 85.3 0.067
The mean values and mean changes are given for eight health concepts at inclusion (baseline), 12 weeks after diet intervention, and 16 weeks after the end of diet
intervention (week 28). The 95% condence interval with higher and lower limits are shown. Linear mixed model. P-value<0.05 is considered statistically signicant.
Table 4: Evaluation of health-related quality of life using RAND 36-Item Health Survey.
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 8 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
Variable Mean Lower Upper P-value
fasting Glucose (mmol/L)
Baseline 9.71 8.54 10.87
Week 12 7.91 6.55 9.27 <0.001
Week 28 9.28 7.71 10.85 0.466
HbA1c (mmol/mol)
Baseline 61.57 56.42 66.72
Week 12 49.20 44.02 54.38 <0.001
Week 28 54.36 48.83 59.90 0.002
C-peptide (nmol/L; serum)
Baseline 0.99 0.82 1.17
Week 12 0.88 0.70 1.05 0.015
Week 28 0.88 0.68 1.09 0.108
Zonulin (ng/ml; serum)
Baseline 79.9 71.3 88.5
Week 12 92.9 83.5 102.3 0.019
Week 28 95.1 84.2 105.9 0.014
Zonulin (ng/ml; feces)
Baseline 49.4 38.3 60.4
Week 12 92.3 71.3 113.2 <0.001
Week 28 53.5 40.4 66.6 0.572
Weight (kg)
Baseline 89.8 84.5 95.1
Week 12 83.6 78.1 89.0 <0.001
Week 28 85.4 79.7 91.1 <0.001
BMI (kg/m2)
Baseline 29.9 28.4 31.3
Week 12 27.8 26.3 29.4 <0.001
Week 28 28.4 26.8 30.0 <0.001
Waist circumference (cm)
Baseline 107.3 103.4 111.2
Week 12 100.3 96.1 104.4 <0.001
Week 28 101.7 97.6 105.9 <0.001
BMI=Body Mass Index, Hba1c=Hemoglobin A1c. The mean values and 95% condence interval with lower and upper and lower limits are presented for fasting plasma
levels of glucose and blood levels of hba1c at inclusion (baseline), 12 weeks after diet intervention, and 16 weeks after the end of diet intervention (week 28). Linear mixed
model. p-value<0.05 was considered statistically signicant.
Table 5: Anthropometric and metabolic biomarkers.
Psychological well-being Abdominal pain Diarrhea Bowel symptoms inuence on daily life
Vitality rs=0.476
p=0.008
rs=0.412
p=0.024
rs=0.418
p=0.021
General Health rs=0.401
p=0.028
Social
Functioning
rs=0.438
p=0.001
Mental Health rs=0.436
p=0.018
There were no other correlations between items in Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS) and RAND-36. Spearman´s rank correlation test. P<0.05
was considered statistically signicant.
Table 6: Correlation between the participants scoring for items in VAS-IBS and RAND-36.
patients with diabetes type 2 [37], who are known to have poor HRQoL
[38]. e improvement of gastrointestinal symptoms and HRQoL
among the participants in the present study could not be explained
by weight reduction, improved metabolic control or altered hormonal
prole. Rather, the positive aspects of enrollment in a clinical trial and
all the positive attention is accomplished with better psychological
health [39]. Also central reward systems may be aected, not possible
to estimate in peripheral blood samples [6]. e improved well-being
at week 12 preceded the decreased gastrointestinal symptoms at week
28. is suggests that the diminished symptoms are due to a better
psychological status rather than the food intervention per se. On the
other hand, most participants continued with a healthy breakfast, high
intake of fruits and vegetables, and regular meals. ese improved food
habits may have led to less gastrointestinal symptoms over time.
One of the most remarkable changes for the participants in the
present study was the introduction of breakfast and regular meals.
ere is a strong evidence for that intake of breakfast cereals and regular
meals are associated with better well-being and metabolic control and
less gastrointestinal symptoms [10,40]. By eating breakfast, important
cereals are ingested, which are associated with overall healthier life style
habits and lower mortality [41,42]. us, intake of breakfast and regular
meals may per se, independent of dietary content, be of importance for
Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017) High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of Anthropometric Hormonal and Metabolic Factors. J Diabetes
Metab 8: 733. doi: 10.4172/2155-6156.1000733
Page 9 of 10
Volume 8 • Issue 3 • 1000733
J Diabetes Metab, an open access journal
ISSN: 2155-6156
healthy habits and lower prevalence of gastrointestinal symptoms [10].
More and regular meals render diminished intervals between meals,
which renders improved nutrition utilization [43].
A previous association study did not show any association between
BMI and gastrointestinal symptoms in an overweight population [44].
In population-based studies, BMI was associated with abdominal pain,
diarrhea, and vomiting in one study [45,46] but not in another [10]. In
young students, a correlation between constipation-predominant IBS
and BMI was found [47]. Only a few patients in the present cohort had
any gastrointestinal complaints. Among those who had complaints,
some had worsened trouble aer introduction of the ber-rich diet
with increased constipation and bloating. us, the results are not
comparable to epidemiological studies where obesity is associated with
an unhealthy diet and low physical activity [45,46].
Zonulin has been introduced as a biomarker of increased intestinal
permeability [13], and theoretically, is therefore an interesting molecule
to measure in patients with gastrointestinal symptoms and diseases.
However, in this and previous studies in health and type 2 diabetes,
zonulin levels were not associated with gastrointestinal symptoms,
but with metabolic factors such as weight, waist circumference, blood
pressure, and glucose levels [14,48]. us, zonulin is rather a marker of
metabolic diseases than of gastrointestinal diseases and symptoms [48].
One limitation of the present pilot study is that only fasting levels
of hormonal and metabolic factors were measured, whereas the
subjective estimation of satiety and sweet cravings reected overall
feeling during the day. e lack of assessment of satiety at inclusion
may also be of importance. e limitation of the present study is the
absence of control group. However, a previous breakfast study showed
that a single breakfast composed of an Okinawan-based Nordic diet,
rendered higher satiety compared with an ordinary composed meal
[12]. Further, a similar study has not shown any changes in metabolic
parameters over the observational time period in a control group [49].
In conclusion, an Okinawan-based Nordic diet with moderately
low carbohydrate content and high ber, fat, and protein contents
renders an increased satiety and reduced sweet cravings, independently
of anthropometric, hormonal, metabolic or psychological factors.
Improved psychological well-being and HRQoL proceeds the reports
of decreased gastrointestinal symptoms.
Acknowledgements
We want to acknowledge Igelosa Life Science AB, Lund, whose staff supplied
and prepared the meals and the staff at the Internal Medicine Research
Group, Skane University Hospital, Malmo, for performing the trials.
This study was supported by grants from Hans-Gabriel and Alice Trolle
Wachtmeister´s Foundation for Medical Research, King Gustaf V:s and
queen Victoria Free Maison´s Foundation, Dir Albert Pahlsson´s Foundation,
Development Foundation of Region Skane, and Foundation of Skane University
Hospital. ClinicalTrials.gov Identier: NCT02405806.
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Citation: Ohlsson B, Darwiche G, Roth B, Bengtsson M, Hoglund P (2017)
High Fiber Fat and Protein Contents Lead to Increased Satiety Reduced
Sweet Cravings and Decreased Gastrointestinal Symptoms Independently of
Anthropometric Hormonal and Metabolic Factors. J Diabetes Metab 8: 733. doi:
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