ArticlePDF Available

Effectiveness of the 6 × 6 Dieet® in Obese DMT2 Patients Effectiveness of a Very Low Carbohydrate Ketogenic Diet Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Patients

Authors:
  • Dutch Knowledge of Dietititans on Overweight and Obesity (KDOO)
  • Dieetzorg Friesland

Abstract and Figures

Background: More than a million people in the Netherlands suffer from type 2 diabetes mellitus; 80 percent is overweight or obese. Weight loss through diet is important; low carb diets are increasingly popular in diabetes management. Objective: From preliminary results we concluded that the 6 × 6 dieet® (a very low carbohydrate ketogenic diet) was more effective in patients with type 2 diabetes and overweight or obesity than other diets. To prove its effectivity, we compared the 6 × 6 dieet® (6 × 6) to a moderate Low Carb Diet (LCD) and an Energy-Restricted Diabetes diet (ERD). Design: A retrospective three-arm study in dietitian practices to reduce weight; HBA1C; and use of medication in overweight/obese adults with type 2 diabetes on 6 × 6 (VLCKD); a 50-100 grams/day LCD; an energy restricted diabetes diet at 3, 6 and 12 months. Results: Data of 344 (n=110; 123; 111 in each study arm) patients from 16 practices were analyzed. More weight loss was seen in patients on 6 × 6, both at a 3, 6, and 12 months follow-up than in patients on LCD or ERD (all p-values <0.05). A total of 34.5% of patients on 6 × 6 turned their HbA1c levels to a value <43 mmol/mol after 12-months follow-up which was a higher proportion than in the LCD study arm (p=0.14) and the ERD study arm (p<0.01). The percentage of patients that stopped or reduced their use of Metformin, SU derivatives or Insulin was larger in the 6 × 6 study arm than in the LCD ad ERD study arms, reaching statistical significance when comparing 6 × 6 with ERD. Conclusions: 6 × 6 was more effective than LCD or ERD in overweight or obese patients with type 2 diabetes regarding weight loss, remission of type 2 diabetes, HbA1c-levels, and the reduction of diabetes medication. Keywords: BMI; Low carbohydrate diet; DMT2 2; HbA1c; VLCKD; 6 × 6; Insulin; Metformin; Sulfoneum derivatives; Weight loss; Diet; Dietitian; Duration of treatment; Primary care
Content may be subject to copyright.
Sci Forschen
Open HUB for Sc i e n t if i c R e s e a r c h
Internaonal Journal of
Endocrinology and Metabolic Disorders
ISSN 2380-548X | Open Access
Int J Endocrinol Metab Disord
| IJEMD
1
RESEARCH ARTICLE
Eecveness of the 6 × 6 Dieet® in Obese DMT2 Paents
Eecveness of a Very Low Carbohydrate Ketogenic Diet Compared to a Low
Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes
Paents
Elisabeth Govers1,2*, Anniek Otten3, Beatrijs Schuiling3, Wilma Bouwman4, Alie Lourens4, and Tommy LS Visscher1,5
1Dutch Knowledge Centre for Dieans specialized on Overweight and Obesity, The Netherlands
2Department of dietecs, Amstelring, foundaon for primary Care, The Netherlands
3Hanzehogeschool (HEI), department of nutrion and dietecs, Groningen, The Netherlands
4Dieetzorg Friesland, Leeuwarden, The Netherlands
5Windesheim University of Applied Sciences, Research group Healthy city, Zwolle, The Netherlands
Received: 01 Aug, 2019 | Accepted: 30 Aug, 2019 | Published: 06 Sep, 2019
Volume 5 - Issue 2
*Corresponding author: Elisabeth Govers, Cornelis van Alkemadestraat 16, 1065 AC Amsterdam, The Netherlands, Tel: +31(0)629177565;
Email: e.govers112@upcmail.nl
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab Disord
5(2): dx.doi.org/10.16966/2380-548X.158
Copyright: © 2019 Govers E, et al. This is an open-access arcle distributed under the terms of the Creave Commons Aribuon License,
which permits unrestricted use, distribuon, and reproducon in any medium, provided the original author and source are credited.
Abstract
Background: More than a million people in the Netherlands suer from type 2 diabetes mellitus; 80 percent is overweight or obese. Weight loss
through diet is important; low carb diets are increasingly popular in diabetes management.
Objecve: From preliminary results we concluded that the 6 × 6 dieet® (a very low carbohydrate ketogenic diet) was more eecve in paents with
type 2 diabetes and overweight or obesity than other diets. To prove its eecvity, we compared the 6 × 6 dieet® (6 × 6) to a moderate Low Carb
Diet (LCD) and an Energy-Restricted Diabetes diet (ERD).
Design: A retrospecve three-arm study in diean pracces to reduce weight; HBA1C; and use of medicaon in overweight/obese adults with type
2 diabetes on 6 × 6 (VLCKD); a 50-100 grams/day LCD; an energy restricted diabetes diet at 3, 6 and 12 months.
Results: Data of 344 (n=110; 123; 111 in each study arm) paents from 16 pracces were analyzed. More weight loss was seen in paents on 6 × 6,
both at a 3, 6, and 12 months follow-up than in paents on LCD or ERD (all p-values <0.05). A total of 34.5% of paents on 6 × 6 turned their HbA1c
levels to a value <43 mmol/mol aer 12-months follow-up which was a higher proporon than in the LCD study arm (p=0.14) and the ERD study arm
(p<0.01). The percentage of paents that stopped or reduced their use of Meormin, SU derivaves or Insulin was larger in the 6 × 6 study arm than
in the LCD ad ERD study arms, reaching stascal signicance when comparing 6 × 6 with ERD.
Conclusions: 6 × 6 was more eecve than LCD or ERD in overweight or obese paents with type 2 diabetes regarding weight loss, remission of type
2 diabetes, HbA1c-levels, and the reducon of diabetes medicaon.
Keywords: BMI; Low carbohydrate diet; DMT2 2; HbA1c; VLCKD; 6 × 6; Insulin; Meormin; Sulfoneum derivaves; Weight loss; Diet; Diean;
Duraon of treatment; Primary care
type 2 diabetes mellitus are overweight and obesity: present in 80
percent of patients with DMT2 [3]. Weight loss is the main strategy to
manage type 2 diabetes and this can be achieved by dietary treatment,
preferably in combination with physical training [4-7]. Diet therapy
and health promotion are eective strategies to lose weight, improve
HbA1c, reduce CVD risk factors and diabetes medication and to
improve quality of life [4-8]. Patients with type 2 diabetes are also
Introduction
More than one million out of a total of 17 million people in the
Netherlands suer from type 2 diabetes mellitus [1,2]. e number of
people with the disease is still accumulating and is a growing burden
on both societal and individual level, because of the complications
like cardiovascular disease and early death [3]. Main risk factors for
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
2
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
insulin resistant. Weight loss is the best way to reduce insulin resistance
[9,10]. e impact of carbohydrates on poor weight loss and poor
insulin production is conrmed by the impact that low carbohydrate
diets have on weight loss and HbA1c. ere is evidence that insulin
resistance is treated best with a very low carbohydrate diet [9,10].
e rationale behind administering very low carbohydrate diets is
that patients with a large accumulation of abdominal fat are almost all
Insulin Resistant (IR), causing high insulin levels, even between meals
[8,11]. High insulin levels promote the storage of carbohydrates as
triglycerides (lipogenesis) causing weight gain. is is one of the main
reasons why patients have trouble to lose weight on diets with normal
quantities of carbohydrates, and to maintain their achieved weight
loss. Very low carbohydrate ketogenic diets, like the 6 × 6 diet®, reduce
the release of endogenic insulin from the pancreas to a minimum, thus
causing there lease of triglycerides from the fatty tissue (lipolysis);
enhance gluconeogenesis by the liver; and furthermore promote the
release of growth hormone, thus raising energy expenditure. e
ketones that are formed probably have interaction with ghrelin and
leptin, causing lowered appetite [12]. ese mechanisms together
lead to extensive weight loss [9], and sometimes remission of type 2
diabetes. Protein requirement is >1 gram per kilo present body weight
per day, which means it is a high protein diet. High protein intake
minimalizes the lost muscle mass; in combination with increased fat
intake it produces fast and long-lasting satiety [9,13], reducing craving
for food and feelings of hunger, which might contribute to better
compliance.
During recent years low carbohydrate diets have become more
popular, because of their eect on weight loss, improvement of
HbA1c and on the reduction or end of medication [9,10,14,15]. Low
carbohydrate diets can vary from a ≤ 10 energy % (20-50 grams) Very
Low Carbohydrate Ketogenic Diet to a ≤ 26 energy % (70-120 grams)
Low Carbohydrate Diet (LCD) per day [16]. A restriction of less than
50 grams per day is eective on the short term [16,11]. Until now
studies have compared the eects of low carb and moderate carb diets
on weight loss and HbA1c [13], but the dierence between Very Low
Carbohydrate Ketogenic Diet and LCD has not been fully established.
Based on the impact of carbohydrates on poor weight loss and
increasing HbA1c levels, we hypothesize that diets are most eective
on weight loss and HbA1c levels in case carbohydrate intake is lowest.
ere is one restriction. Studies have revealed that humans need 36
grams of carbohydrate as a minimum level of intake in order to avoid
a shortage of glucose in the brain. e carbohydrate need of the brain
and the erythrocytes is estimated on 36 grams per day average [11], but
there are considerable interpersonal dierences [9]. e 6 × 6 dieet® is
a VLCKD with 36 grams of carbohydrates per day administered in a
strict scheme, meaning that the patient eats 6 times per day 6 grams
of carbohydrates, preventing insulin release by the pancreas [10,17].
Preliminary research in Dutch patients receiving the 6 × 6 dieet®
showed more weight loss, lower HBA1C and reduction or stopping
of medication than the more conventional low carbohydrate diets
aiming at higher carbohydrate intake. Inspired by these preliminary
results, we decided to compare the 6 × 6 dieet®’s impact on weight loss
and HbA1c with the impact of less strict low carbohydrate diet and
an energy-restricted diet, which has been common practice during
the last decades, among patients with DMT2. Our research question
was: “What is the dierence in eectiveness between the 6 × 6 dieet®
and other low carbohydrate diets and energy-restricted diets for adults
(18+) with type 2 diabetes who are overweight or obese regarding to
weight loss, improving HbA1c levels, use of metformin, SU-derivatives
and insulin at a 3, 6 and 12 month follow-up?”
Methods
Study design
We collected existing data from patients who have been administered
the 6 × 6 dieet® and from patients who had been administered a Low
Carbohydrate Diet (LCD) or an Energy Restricted Diet (ERD)and
carried out a retrospective research to study whether the 6 × 6 dieet®
is more eective on weight loss and HbA1c than the LCD and ERD.
Some 300 practices of dietitians in the Netherlands use low carb diets
for diabetes management [18].
Participants
Two dietitians (WB & AL) from the same center (Dieetzorg
Friesland) developed and registered the 6 × 6 dieet®. ey have
administered the diet to patients from December 2013 onwards until
September 2016. eir full data were used on patients being diagnosed
with type 2 diabetes mellitus receiving the 6 × 6 diet was used to study
the eectiveness of the 6 × 6 diet.
Dietitians administering a Low Carbohydrate Diet (LCD) and/or an
Energy Restricted Diet (ERD) to patients with type 2 diabetes across
e Netherlands were invited to deliver their data for the purpose of
the present study. Members from the Knowledge Centre for Dietitians
for Overweight and Obesity (KDOO) were recruited through the
KDOO newsletter (https://www.kdoo.nl) and we published a call
in the digital newsletter on the website of the Dutch Association of
Dietitians (https://www.nvdietist.nl/NieuwsvoorDietisten). e
Dutch Association of Dietitians awarded ‘points for accreditation’ for
‘participating in research activities.’ Dietitians that applied, were sent
the study protocol by email. Two students from the department of
Nutrition and Dietetics of Hanzehoge school, an University of Applied
Sciences in Groningen, e Netherlands, carried out the data collection
by going to the dietary practices from across the country. Dietitians
that took part in the study collected at least 15 subsequent patients per
dietitian from September 2016 till 1st of March 2017, who were treated
for type 2 diabetes, and who fullled the inclusion criteria. AO and BS
decided whether an included patient was labeled as being administered
an LCD or ERD, based on the carbohydrate intake of the patient as
agreed aer the rst consultation: less than 50 grams in the very low
carbohydrate ketogenic study arm, less than 100 grams carbohydrates
(≤ 26 en%) in the low carb study arm; more than 100 grams of carbs
in the energy restricted study arm, which is in practice also mono and
disaccharide and SAFA restricted. Energy restricted diets had more
than 100 grams of carbohydrates per day. Ninety percent of dietitians
in primary care work with the same soware (Evry). Dietitians were
asked to collect data in this program. Data were collected on gender,
age, body weight and height, HbA1c, use of medication, number of
consultations and duration of the treatment in minutes at baseline, 3,
6 and 12 months. Data were also recorded regarding the number of
consultations and treatment duration. AO and BS collected these data
in situ and uploaded them in Excel.
In and exclusion criteria
Inclusion criteria were: Adults aged 18 years, or older with BMI ≥
25 kg/m2 and diagnosed with type 2 diabetes, by a general practitioner,
dened as fasting glucose ≥ 7.1 mmol/l (127.8 mg/dl) twice or more
at several days and/or HbA1c ≥ 43 mmol/l, not necessarily conrmed
by lab values for fasting glucose; intake between 01-09-2016 and 01-
03-2017. Exclusion criteria were prednisolone or other corticosteroids,
any treatment for oncology, other hormonal treatments, pregnancy,
unplanned weight loss by another disease, because of their potential
impact on weight change.
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
3
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
Description of diets: Table 1 shows the dierences between the
three diets. e 6 × 6 dieet® (in this study called 6 × 6) was originally
developed by the Dutch Knowledge Centre of Dietitians specialized
in Overweight and Obesity in 2013 [10]. e diet comprises of three
phases: a rst Very Low Carbohydrate Ketogenic Diet phase with 6
× 6 grams of carbohydrates per day; a second phase with a rise in
carbohydrates up to 6 × 12 grams of carbohydrates per day (maximum
75 grams); and a maintenance phase with a higher carbohydrate
content up to the level that weight loss stops. Dieetzorg Friesland
further developed already existing materials for patients and became
very strict in the protein content of the diet: at least 1 gram per kilo
present body weight. ere is no restriction on calorie intake and
fat intake and no rules about SAFAs in the rst phase. e diet is
administered following a strict protocol and much time is invested
in teaching patients how to deal with it in daily life [13]. e low
carbohydrate diet (LCD) oers a carbohydrate intake of 50-100 grams
per day (equaling ≤ 26 energy %); a protein intake of 1 gram/kg present
body weight and 30-35 energy percent fat. e energy-restricted diet
(ERD) implies a moderate carbohydrate intake, with restriction of
mono- and disaccharides, a protein intake of 0.8 gram/kg ideal body
weight and a reduced fat intake of 30-35 energy percent.
HbA1c and medication: Data on HbA1c were available for 283
(82.3%) patients at baseline and for 186 (81.9%) patients at time-point
12 months. Patients with missing data on HbA1c were included in all
our analyses, except for the analyses on Hb1Ac. Dosage of diabetes
medication was recorded regarding metformin, SU-derivates and
insulin used 3, 6 and 12 months.
Ethics
We informed dietitians that taking part in the study was voluntary
and that their decision to participate or to not participate would
not aect their relations with the knowledge center for Dietitians
for Overweight and Obesity or the Dutch Association of Dietitians.
ey were also informed that data would be analyzed and presented
anonymously, meaning that dietitians involved in the study and the
two students analyzing the data would not be able to present or reveal
results on the level of the patient nor on the level of dietitian center.
e research leader (TLSV) re-coded all centers and did and will not
share the key to these codes. e research leader, not being a dietitian,
does not have any relation to the dietitian centers, and he does not
know names behind the participant numbers. Asking ethical approval
from the medical-ethical committee was not needed, as data had been
recorded in the past as part of normal intervention procedures, patients
personal data remained unknown to the researchers, and data were
analyzed and presented anonymously. Dietitians were free whether to
inform their patients that their data had been used. We advised that
informing patients was not necessary, as to avoid unnecessary worry
amongst patients, and because we assumed that centers lack 100%
information regarding patients current address or whether they are
still alive. Treatment of all patients had already been nished, and
therefore results were not inuenced.
Statistical analysis
Baseline characteristics are compared between study arms. Average
weight loss and decline in HbA1c between the baseline and time-points
at 3, 6, and 12 months were compared between study arms. Amongst
those with HbA1c ≥ 43 mmol/mol, we calculated the percentage of
subjects who had lowered their HbA1c to <43 mmol/mol and we
compared these percentages across study arms. Further, we calculated
the percentage of patients stopping or reducing the dosage of their
medication and the percentage of patients losing >5% and losing
>10% aer 1 year, respective to their weight at baseline. We compared
these percentages across the study arms. And, we calculated whether
the relative weight loss (weight loss as a percentage of initial body
weight) diered across study arms, within categories of BMI (BMI 25-
29.9, 30-34.9, and ≥ 35 kg/m2. Comparisons across study arms were
tested by Fisher’s Exact test (for binary variables), Pearson Chi-square
(for categorical variables), and independent samples T-test, assuming
equal variances (for continuous variables). e 6 × 6 study arm was
used as the reference study arm in all comparisons.
Intention to treat analysis was performed by calculating the number
of patients losing 5% or more from their initial body weight over a
year follow-up divided by the number of all 344 patients at baseline
starting the diet, including those lost to follow-up, plus those who
were initially excluded from the analyses due to stopping diet within
a month (n=1, on 6 × 6 diet), hormone treatment from the start (n=1,
on 6 × 6), receiving hormone treatment to prevent transplant rejection
(n=1, on 6 × 6), starting prednisolone within rst three months (n=15,
of which 2 were on 6 × 6 diet, 4 were on LCD and 9 were on ERD) or
starting prednisolone between months 6 and 12 (n=2, both on 6 × 6
diet). Further, total treatment time and the number of consultations
averages between 6 × 6; LC and ER diets were compared. Data were
analyzed in SPSS version 25. Statistically signicance was considered
in case p<0,05.
Results
Data were collected from 16 practices with a wide national
dispersal. Figure 1 shows the study ow chart with included patients
and drop-out rates. Initially, we collected data of 380 patients. A total
of 36 patients were excluded from the analyses. Finally 110 patients
Diet Calories Protein Carbohydrate Fat Fibre
6×6 dieet® (6×6),
a VLCKD
No calorie
restricon
≥ 1 gram per kg
present body
weight
Phase 1: 6 × per day six grams;
Phase 2: max 75 grams; Phase 3:
individually assessed
No fat restricon. 1st and 2nd phase:
no rules about kind of fat (SAFA;
MUFA or PUFA)
No strict amount.
Based on intake
Low
carbohydrate
(LCD)
No calorie
restricon
1 gram per kg body
weight, up to 100
grams per day
50-100 grams per day 30-35% of energy% emphasis on
MUFA and PUFA
No strict amount.
Based on intake
Energy-
restricted (ER)
Restricted -
600 kcal of
usual intake
0.8 grams per kg
ideal body weight
or BMI 27 kg-m2
≥ 100 grams per day 30-35% of energy% emphasis on
MUFA and PUFA 30 g/day
Table 1: Criteria for the 6 × 6 dieet®, low carbohydrate diet and energy-restricted diets.
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
4
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
on the 6 × 6 diet; 123 patients the LCD; and111 patients the ERD
were included in the analysis. Reasons for exclusion were age <18
years (n=1), unknown diet (n=2), insucient data on body weight or
height (n=4), BMI <30 kg/m2 (n=9), stopping the diet within a month
(n=1), start of hormone treatment from the start (n=1), medication
to prevent transplant rejection (n=1), and starting prednisolone use
during the study period (n=17). Aer 12 months 227 patients (66%)
were still in treatment. Drop-out rates were lower in the 6 × 6 (31%)
and LCD (30%) study arms than in the ERD (42%) study arm.
e study population is presented in table 2. e percentage of
females and age were similar across the three study arms. Patients
receiving the 6 × 6 diet had a longer history of type 2 diabetes: 70.0%
had type 2 diabetes for 3 years or longer in the 6 × 6 study arm,
compared with 56.4% in the LCD and 44.9% in the ERD study arm.
Less patients had overweight both in the 6 × 6 and LCD study arms.
Mean weight in the 6 × 6 arm was higher (p=0.05). e percentage
of BMI higher than 35 kg/m2 and mean BMI were highest in the 6 ×
6 study arm, although statistical signicance was only reached when
comparing mean BMI between 6 × 6 and LCD study arms (p=0.02).
More patients in the 6 × 6 study arm were using metformin or insulin.
SU-derivates were prescribed equally across study arms. Mean HbA1c
at baseline was lowest in the 6 × 6 study arm, statistically signicantly
compared to mean HbA1c in the LCD study arm: 57.6 and 63.6
(p=0.01); but not in ECD 59.7 (p=0.32).
Baseline
3 months
6 months
12 months
Total number of patients: n=380
Excluded: (n=36)#
Age < 18 years, n=1
Diet unknown, n=2
Insufficient data BMI, n=4
BMI <30 kg/m2, n=9
Stopped diet within a
month, n=1
Hormone treatment from
start, n=1
Medication to prevent
transplant rejection, n=1
Prednisolone use within
3 months, n=15
Prednisolone use between
months 6 and 12, n=2
Total patients included: 344
6x6 diet
“6x6”
(n=110)
“LCD”
(n=123)
Energy restricted diet
“VLCD”
(n= 111)
6x6 diet
(n=105)
(n=117)
Energy restricted diet
(n= 99)
6x6 diet
(n=93)
(n=100)
Energy restricted diet
(n= 79)
6x6 diet
“6x6”
(n=76)
“LCD”
(n=87)
Energy restricted diet
“VLCD”
(n= 64)
Figure 1: Flow chart of number of paents in the three study arms.
# Notes: The one subject that stopped within a month was on 6 × 6 diet. From the subjects who started prednisolone use between the start and
month three, 2 were on the 6 × 6 diet, 4 were on a low carb diet, and 9 were on energy restricted diet. The 2 subjects that started prednisolone
use between months 6 and 12 were on the 6 × 6 diet. The 1 subject that started hormone treatment from the start and the 1 subject that started
medicaon to prevent transplant rejecon were on the 6 × 6 diet.
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
5
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
Figure 2: Average weight loss in kilos per diet aer 3, 6 and 12 months.
The dierence in weight loss between the 6 × 6 diet and the low carbohydrate diet and between the 6 × 6 diet and the energy restricted diet was
stascally signicant at 3, 6 and 12 months.
Data available, n
6 × 6 LCD ERD Total P P
N=110 N=123 N=111 N=344 6 × 6 vs LCD 6 × 6 vs ERD
Percentages
Male/female 343 39/61 42/58 51/49 44/56 0.69 0.11
Meormin 333 64.5 58.8 51.9 58.6 0.42 0.07
SU-derivates 344 27.3 28.5 25.2 27 0.88 0.76
Insulin 344 31.8 16.3 15.3 20.9 <0.01 <0.01
Years with DM2
336 0.03 <0.01
<1 15.5 29.9 30.3 25.3
>1t/m <3 14.5 13.7 24.8 17.6
>3 t/m <10 48.2 45.3 27.5 40.5
≥ 01 21.8 11.1 17.4 16.7
BMI (kg/m2)
344 0.48 0.09
25.0-29.9 21.8 22.8 35.1 26.5
30.0-34.9 40 46.3 33.3 40.1
≥ 0.53 38.2 30.9 31.5 33.4
Mean (standard deviaon)
Age (years) 344 60.8 (10.9) 62.1 (10.8) 62.1 (11.1) 61.7 (10.9) 0.38 0.41
BMI (kg/m2)344 34.5 (5.6) 32.9 (4.5) 33.1 (5.6) 33.5 (5.3) 0.02 0.06
Weight (kg) 344 102.2 (17.9) 97.5 (18.0) 98.6 (18.6) 99.4 (18.0) 0.05 0.15
HbA1c (mmol/mol) 283 57.6 (13.5) 63.6 (18.6) 59.7 (15.1) 60.4 (16.1) 0.01 0.32
Table 2: Baseline characteriscs of the study populaon.
Weight loss
Patients in the 6 × 6 study arm lost 2.3 (95% CI: 1.1-3.5), 3.0 (95%
CI: 1.2-4.7) and 2.7 (95% CI: 0.5-4.8) kg more, after 3, 6, and 12
months, respectively, than patients in the LCD study. Compared to
those in the ERD study arm, patients in the 6 × 6 study arm lost 3.9
(95% CI: 2.8-5.1), 3.7 (95% CI: 2.0-5.4) and 3.5 (95% CI: 1.0-6.0)
kg, more after 3, 6, and 12 months, respectively.These results are
presented in gure 2.
e mean relative weight loss, calculated as weight loss divided by
body weight at baseline, was 8.7% in the 6 × 6 study arm, which was
higher than in the LCD study arm (6,4%, p=0.02) and higher than in
the ERD study arm (5.8%, p=0.01). Also, within each category of BMI
relative weight loss was higher in the 6 × 6 study arm than in the LCD
and ERD study arms, but statistical signicance was not reached when
comparing these relative weight losses across study arms within BMI
categories (Table 3).
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
6
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
Table 4 shows that the percentage of patients losing 5% or more and
the percentage of patients losing 10% of their initial body weight were
higher in the 6 × 6 study arm than in the LCD and ERD study arms,
although dierences were statistically signicant only when 6 × 6 was
compared with ERD, not when compared with LCD. e intention to
treat analysis made clear that at least 43.2% of patients in the 6 × 6
study arm lost 5% or more from their weight at baseline; compared
with 41.7% (p=0.90) in the LCD and 23.3% (p<0.01) in the ERD study
arm. At least 22.9% of patients in the 6 × 6 study arm lost 10% or more
from their weight at baseline, compared with 17.3% (p=0.34) in the
LCD and 10.0% (p=0.01) in the ERD study arms.
HbA1c
Figure 3 shows that the improvement of HbA1c was similar in the 6
× 6 and in the LCD study arm at 3, 6, and 12 months. At 12 months, the
decline in LCD study arm was 2.6 (95% CI: -2.5-7.7) mmol/mol larger
than in the 6 × 6 study arm, although the average level was lower in 6
× 6 (63.6/49.7 LCD, and 57.6/47.1 6 × 6 respectively). e decline of
HbA1c in the 6 × 6 study arm was statistically signicantly larger than
in the ERD larger at 3 and 6 months, not at 12 months. At time-point
12 months, decline in HbA1c in the 6 × 6 study arm was 1.6 (95% CI:
-3.9-7.0) mmol/mol larger than in the ERD study arm.
Amongst patients with HbA1c of ≥ 43 mmol/mol at baseline, 34.5%,
20.7%, and 9.3%, had lowered their HbA1c to < 43 mmol/mol at time-
point 12 months in the 6 × 6, LCD, and ERD study arm, respectively
(6 × 6 versus LCD p=0.14; 6 × 6 versus ERD p<0.01) (data not shown).
Medication
Table 4 shows the reduction in medication use per study arm. e
reduction in the use of Metformin was highest in the 6 × 6 study arm
at 3, 6, and 12 months, although not reaching statistical signicance
when comparing with the LCD study arm at 3 months. e reduction
in use of SU-derivates was also highest in the 6 × 6 study arm, but
only reaching statistical signicance when comparing with the ERD
study arm, at 3, 6, and 12 months (Table 5). Aer 12 months, reduction
in insulin use was highest in the 6 × 6 study arm, but only reaching
statistical signicance when comparing with ERD.
Number of consultations and duration of treatment: Data on
number of consultations and treatment duration were available for 333
patients. Patients on 6 × 6 visited their dietitian 7.5 times during the
follow-up period. Patients on LCD and ERD visited their dietitian 5.7
times (p<0.01) and 5.4 times (p<0.01), respectively.
Average total treatment duration was 305 minutes (5.08 hours) for
patients on 6 × 6, which was 89 (95% CI: 66-113) minutes longer than
on LCD, and 89 (95% CI: 62-115) minutes longer on ERD.
Discussion
is retrospective study makes clear that weight loss aer 12
months was greater in patients on a 6 × 6 dieet® than in patients on a
Low Carbohydrate Diet (LCD) or an Energy Restricted Diet (ERD).
Decrease in HbA1C levels was larger in the 6 × 6 study arm than in the
ERD study arm. More patients in the 6 × 6 study arm had stopped or
reduced their intake of metformin SU derivates, and insulin aer 12
months than in the LCD and ERD study arms.
Dispersal of the study population
Because the Netherlands is a small country, where the low
carbohydrate diet has already spread out to most dietary and medical
practices, our study population can be seen as representative for
primary healthcare in the whole country.
One drawback of delivering data by invitation is that dietitians may
be more willing to participate in case they feel comfortable regarding
their own success. If this phenomenon is true, we argue that our
selection procedure has led to an under-estimation of the dierences
with the 6 × 6 diet rather than to an over-estimation. Hence, all data
available regarding the 6 × 6 diet have been used, whereas data on the
other two diets were retrieved by invitation.
One drawback of our selection procedure regarding study-arms is
heterogeneity between the arms, despite targeting a specic patient
population: diabetic patients with overweight. As body weight and
body mass index values diered across study-arms, we have also
presented results per BMI-category. It is important to note that these
BMI-specic analyses did not lead to other insights regarding the
eectiveness of the diets.
Impact on weight loss
e positive results on weight loss are in line with a systematic
review that found a 2.5 kg dierence in weight loss between very low
Figure 3: Decline in HbA1c in the 6 × 6; LC and ER diets.
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
7
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
carbohydrate and moderate carbohydrate diets in patients with DMT2
aer 3-6 months [17]. In our study patients on 6 × 6 had 2.7 kg more
weight loss compared to LCD and 3.5 kg greater weight loss compared
to ERD aer 12 months. e dierence in weight loss in our study in
favor of 6 × 6 is still present at that time-point, in contrast to most
trials where these dierences have diminished aer a year [17, 19, 20].
Looking at the mean relative weight loss related to diet and BMI, it is
clear that 6 × 6 shows the best results in patients with a BMI ≥ 30/kg/
m2. In patients with BMI 24.9-29.9/kg/m2 dierences in weight loss are
smaller. e intention to treat analysis reveals a ≥ 5% weight loss in
43.2% of patients on 6 × 6, and a ≥ 10% weight loss in 22.9%, which
clearly is more than on LCD (41.7 and 17.3%), and is signicantly
more than on ERD (23.3 and 10.0%).
To explain why 6 × 6 has the best weight loss results a combination
of factors can be held accountable. First of all the strong restriction
of carbohydrates on 6 × 6, allowing patients 6 times per day a meal
with 6 grams of carbohydrates, during the rst phase which can last
six months, lowers glucose levels in the blood and insulin secretion by
the pancreas, thus changing energy metabolism causing triglycerides
to be used as main energy source, leading to weight loss. Weight loss
can improve insulin sensitivity by changing the function of adipose
tissue [21]. Secondly, a very low carbohydrate diet allows patients
to eat more fat and more protein, which have more satiety than
carbohydrates, partly because they slow down stomach release due to
longer digestion time; and partly because more ketones are produced,
which also reduce appetite [12,22,23]. ese eects have been reported
by patients as pleasant: patients have the feeling they can control their
appetite, which is oen new to them. irdly, high protein intake also
leads to better preservation of muscle mass, which stimulates energy
expenditure, also leading to more weight loss.
Because weight loss, and more specically the loss of visceral and
abdominal fat, is so important in type 2 diabetes management, the
dierences in outcomes on these three diets should not be put aside
lightly. Recently it was suggested to raise the criteria for weight loss in
patients with type 2 diabetes to 10 kg for prevention of comorbidities
[24]. Moreover, there is a strong relationship between weight loss
and glycaemia [24]. A weight loss of 10 kg may mean the dierence
between having a chronic disease and being in remission; or less use
of medication, and postponing or stopping insulin treatment. Patients
should therefore be encouraged to set their weight loss goal as high as
possible.
Reduction of HbA1c
Lower levels in HbA1c are a sign of improving type 2 diabetes. e
larger reduction of HbA1c induced by the 6 × 6 dieet® and by the LCD
than by the ERD is in line with Avenell A, et al. review concluding
that in patients with type 2 diabetes a diet with less than 50 grams of
carbohydrate per day was more eective to lower HbA1c than a low
carb diet of more than 50 grams or an energy-restricted diet aer three
months [25]. ese outcomes were supported by Elhayany A, et al.
who found that weight loss and HbA1c were signicantly reduced on
a low carb Mediterranean diet [26] and Sainsbury E, et al. systematic
review that low carbohydrate diets were more benecial for lowering
HbA1c than moderately restricted or high carbohydrate diets [17].
Body mass index (kg/m2)
25-29.9 30-34.9 ≥ 35 All
Diet
n51 90 86 227
6 × 6 diet 5.8 (4.5) 8.1 (7.1) 10.6 (7.0) 8.7 (6.8)
Low Carbohydrate (LCD) 4.4 (5.1) 5.6 (5.3) 8.4 (5.4) 6.4 (5.5)
Energy Restricted Diet 5.3 (6.9) 4.7 (5.5) 7.4 (6.9) 5.8 (6.4)
p value 6 × 6 vs LCD** 0.43 0.09 0.17 0.02
P value 6 × 6 vs ERD** 0.8 0.07 0.1 0.01
Table 3: Mean relave weight loss* (standard deviaon) aer 12 months,
within categories of body mass index by diet.
*Relave weight loss is calculated as weight loss divided by body weight
at baseline *100 (%)
**p-value calculated by independent samples t-test
Percentage of
paents Percentage of paents
losing weight* losing weight
By intenon to treat**
n ≥ %5 ≥ %01 N ≥ %5 ≥ %01
6 × 6 76 67.1 35.5 118 43.2 22.9
Low Carbohydrate
(LCD) 87 60.9 25.3 127 41.7 17.3
Energy-restricted
(ERD) 64 43.8 18.2 120 23.3 10
P by Fisher’s Exact
6 × 6 vs LCD 0.42 0.17 0.9 0.34
P by Fisher’s Exact
6 × 6 vs ERD 0.01 0.04 <0.01 0.01
Table 4: Percentage of paents losing weight 5% or more and losing 10%
or more from their inial body weight across the study arms.
* For those with full data on body weight at baseline and at 12 months.
**Calculated as the number of paents losing ≥ 5 or 10% weight divided
by the number of all 344 paents at baseline starng the diet, including
those lost to follow-up, plus those who were inially excluded from the
analyses due to stopping diet within a month (n=1, on 6 × 6 diet), hormone
treatment from the start (n=1, on 6 × 6), receiving hormone treatment to
prevent transplant rejecon (n=1, on 6 × 6), starng prednisolone with in
rst three months (n=15, of which 2 were on 6 × 6 diet, 4 were on LCD
and 9 were on ERD) or starng prednisolone between months 6 and 12
(n=2, both on 6 × 6 diet).
6 × 6
Low
Carbohydrate
Energy
Restricted P* P*
Diet Diet 6 × 6 vs LCD 6 × 6 vs ERD
Meormin
3 months 24.6 16.2 8 0.29 0.03
6 months 45.3 25.9 13.3 0.04 <0.01
12 months 62 28 25.6 <0.01 <0.01
SU derivaves
3 months 90 66.7 37.5 0.06 <0.01
6 months 86.7 66.7 41.7 0.13 <0.01
12 months 90 73.3 41.7 0.18 <0.01
Insulin
3 months 85.7 90 88.2 1 1
6 months 85.7 85 70.6 10.26
12 months 88.6 75 58.8 0.26 0.03
Table 5: Percentage of paents that stopped or reduced use of medicaon
at 3, 6, and 12 months.
* P by Fisher’s Exact test
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
8
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
Reduction of HbA1c is a well known phenomenon in low carb diets
for DMT2 with ≤ 26 en%, which equals <100 grams per day, compared
to high carbohydrate diets [27], and conrms our ndings that there
is a direct relationship between the carbohydrate content of the diet
and the HbA1c. On the contrary, a systematic review comparing low
and high carbohydrate diets indicated that a low fat high carbohydrate
intake signicantly increased fasting insulin, and lowered HDL
cholesterol compared with a high fat low carb diet, thus enhancing the
risk of insulin resistance [28].
Reduction of metformin, sulfonylurea derivatives (SU) and
insulin
Our ndings show a signicant reduction in DMT2 medication
aer 12 months which is larger in the 6 × 6 study arm than in the
LCD and ERD study arms, although only statistically signicant
compared to ERD. e decision to reduce or quit medication is
dependent on reduced HbA1c levels. We even found remission of
DMT2 is possible, as dened by HbA1C <43 mmol/mol: 34.5% of
patients in the 6 × 6 study arm reduced their HbA1C to <43 mmol/
mol. In e Netherlands SU-derivatives are the second step in DMT2
management, when metformin is not eective enough [29], leading
to an extra weight gain of 1-3 kg, because of the promotion of insulin
release from the pancreas. In fact, SUs work contrary to the aim of
weight loss [30]. A low carb diet should always be accompanied by a
total stop of SUs, to promote weight loss. Insulin is administered when
SUs do not work eectively enough, leading to more weight gain as
well [30]. e benet of the 6 × 6 dieet® is that the use of insulin, even
in patients with more than 10 years of DMT2, could be reduced or
even stopped, because the very few carbohydrates in the diet are all
used for the brain and erythrocytes.
Professional guidance and adherence to the diet
Very low carbohydrate ketogenic diets can lead to deciencies in
micronutrients and ber, when not carried out well. Patients therefore
need the appropriate guidance of a dietitian [31-34]. Patients in the 6
× 6 had extra consultations to help them get used to the diet; especially
getting used to the high protein, strict low carbohydrate regimen took
time, leading to longer treatment time. Loss to follow-up was larger in
the LC and ER study arms than in the 6 × 6 study arm. Adherence is
likely to be inuenced positively by successful weight loss, especially
in patients that have a long weight loss history with little success.
e good results in glucose values and the reduction of medication
are also positive points reported by patients. Reasons for drop out
can be disappointing weight loss results, lack of motivation, personal
problems, or taking a sabbatical [20]. Patients have numerous weight
loss cycles and relapse oen, before they reach a point where they can
maintain a stable, healthy weight [35]. In a survey of adherence to
diet, patients with type 2 diabetes and their health professional each
viewed barriers dierently [36] patients expressed a dislike for foods
included in meal plans, contrary to the HPs who considered social
environment as a more important barrier. We think therefore, that a
longer treatment time and a exible attitude of the health professional/
dietitian is needed to keep the patient in care and motivated. In 6 × 6
patients had to go by a strict structure, but were free in their choice of
foods, under the condition that they were low in carbohydrates. ey
did not feel the diet as a restriction. Meat, cheese, butter, and several
high protein snacks, e.g. sh and sausage were allowed, giving patients
a lot of freedom in their social life. is may have led in combination
with rather rapid weight loss to better adherence. e fact that
medication could be reduced, creating a feeling that someone’s health
is improving, is also a possible motivator.
Measuring insulin
Insulin resistance is the main reason for prescribing low carbohydrate
diets, but is not diagnosed in primary care practice by measuring
fasting insulin, but indirectly by measuring other values, such as:
BMI; waist circumference; weight loss history; reporting carbohydrate
cravings; and the presence of hypertension; dyslipidemia; or impaired
glucose tolerance. To target the right patients for VLCKD and LCD
diets, we need to measure fasting insulin. A study by Ter Horst KW,
et al. showed that 78% of obese men had higher fasting insulin, 110
versus 63 pmol/l (15.8 mIU/L versus 9.0 mIU/L) and that >74 pmol/l
(10.6 mIU/L) was a cut-o point for insulin resistance with good
sensitivity and specicity in research and in clinical situations [37].
Based on fasting insulin values, we can set specic recommendations
for carbohydrate content in diets for patients with IR; DMT2; and
other comorbidities.
Recommendation for practitioners
A diet that reduces the release of insulin, meaning a low carbohydrate
ketogenic diet, leads to weight loss and restoration of insulin sensitivity
in patients with type 2 diabetes. We therefore advocate to treat patients
with type 2 diabetes rst with a low carbohydrate weight loss diet,
preferably as low as less than 50 grams per day, to see to what extend
the normal glucose metabolism in the body can be restored; and only
when this approach does not lead to improved glucose values start
with medication.
Strengths and weaknesses
Strengths of this study are the length of the study, the national
dispersal and the strict protocol of data collection. e fact that our
study was not a carefully designed RCT but an observational study
from every day dietary practice makes it possible to implement the
results in other patient settings, especially in primary care. e
repeatability of the study and the principles of the diet in daily practice
are high.
Weaknesses were that we did not systematically measure energy
intake and energy expenditure per patient. We collected glucose values
and HbA1c levels from the physician’s oce, and did not measure
them ourselves. Some patients had lower HbA1c levels than 43 mmol/
mol at baseline: in 6 × 6 (n=10, 9.9%); in LCD (n=6, 6.0%); and in ERD
(n=4, 4.9%) at baseline, which may have inuenced positive outcomes
on the number of patients reaching the ≤ 43 HbA1C level in the 6 ×
6 study arm.
Conclusion
e ndings of this retrospective study show that the 6 × 6 dieet®,
a very low carbohydrate ketogenic diet with high protein and no fat
restriction, when consistently performed, produces larger weight loss,
reduction of HbA1c, reduction of diabetes medication in overweight
or obese patients with type 2 diabetes than a milder low carbohydrate
diet or an energy-restricted diabetes diet.
Acknowledgements
e authors wish to thank all dietitians for their willingness and
cooperation in the data collection. ey wish to thank M. Sealy
at Hanze Hogeschool for her feedback on earlier versions of the
manuscript.
Conict of Interest
e authors declare no conict of interest. No one has been paid or
sponsored to collect data, process them, or write the article.
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
9
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
Authorship
EG designed the initial 6 × 6 diet (2013), made the study design
and wrote the article. AO and BS collected all data. AO, BS, and TLSV
carried out the analyses. WB and AL developed the 6 × 6 dieet® and
wrote the study protocol. All authors read, corrected and approved of
the article.
Data Sharing
Data described in the manuscript, codebook, and analytic code will
be made available upon request.
References
1. Tack CJ, Diamant M, de Koning EJP (2012) Handbook diabetes
mellitus. De Tijdstroom, Utrecht, The Netherlands.
2. RIVM (Naonal Instute for Public Health and the Environment)
(2018) Diabetes Mellitus-Huidige situae,Volksgezondheid en zorg.
Translaon: Diabetes Mellitus-present-situaon in The Netherlands.
3. Visscher TL, Seidell JC (2001) The public health impact of obesity.
Annu Rev Public Health 22: 355-375.
4. Andrews RC, Cooper AR, Montgomery AA, Norcross AJ, Peters TJ,
et al. (2011) Diet or diet plus physical acvity versus usual care in
paents with newly diagnosed type 2 diabetes: the Early ACTID
randomised controlled trial. Lancet 378: 129-139.
5. Wolf AM, Conaway MR, Crowther JQ, Hazen KY, L Nadler J, et al.
(2004) Translang lifestyle intervenon to pracce in obese paents
with type 2 diabetes: Improving Control with Acvity and Nutrion
(ICAN) study. Diabetes Care 27: 1570-1576.
6. Coppell KJ, Kataoka M, Williams SM, Chisholm AW, Vorgers SM, et al.
(2010) Nutrional intervenon in paents with type 2 diabetes who
are hyperglycaemic despite opmised drug treatment-Lifestyle Over
and Above Drugs in Diabetes (LOADD) study: randomised controlled
trial. BMJ 341: c3337.
7. Basta MC, Labonté M, Ménard J, Jean-Denis F, Houde G, et
al. (2012) Diean-coached management in combinaon with
annual endocrinologist follow up improves global metabolic and
cardiovascular health in diabec parcipants aer 24 months. Appl
Physiol Nutr Metab 37: 610-620.
8. Knowler WC, Fowler SE, Hamman RF, Christophi CA, Homan HJ, et
al. (2009) 10-year follow-up of diabetes incidence and weight loss
in the Diabetes Prevenon Program Outcomes Study. Lancet 374:
1677-1686.
9. Paoli A, Rubini A, Volek JS, Grimaldi KA (2013) Beyond weight loss: a
review of the therapeuc uses of very-low-carbohydrate (ketogenic)
diets. Eur J Clin Nutr 67: 789-796.
10. Govers E, Slof E, Verkoelen H, Ten Hoor-Aukema NM, KDOO, et al.
(2015) Guideline for the Management of Insulin Resistance. Int J
Endocrinol Metab Disord 1.
11. Tay J, Luscombe-Marsh ND, Thompson CH, Noakes M, Buckley JD,
et al. (2014) A Very Low-Carbohydrate, Low-Saturated Fat Diet for
Type 2 Diabetes Management: A Randomized Trial. Diabetes Care
37: 2909-2918.
12. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, et
al. (2013) Ketosis and appete-mediang nutrients and hormones
aer weight loss. Eur J Clin Nutr 2013: 759-764.
13. Sainsbury E, Kizirian NV, Partridge SR, Gill T, Colagiuri S, et al. (2018)
Eect of dietary carbohydrate restricon on glycemic control
in adults with diabetes: A systemac review and meta-analysis.
Diabetes Res Clin Pract 139: 239-252.
14. Ajala O, English P, Pinkney J (2013) Systemac review and meta-
analysis of dierent dietary approaches to the management of type
2 diabetes. Am J Clin Nutr 97: 505-516.
15. Santos FL, Esteves SS, da Costa Pereira A, Yancy WS Jr, Nunes JP
(2012) Systemac review and meta-analysis of clinical trials of the
eects of low carbohydrate diets on cardiovascular risk factors.
Obes Rev 13: 1048-1066.
16. Govers E (2017) Low Carb High Protein Diets as Management Tool of
Insulin Resistance in Paents with Obesity and/or Type 2 Diabetes
Mellitus. Obes Open Access 3.
17. Dieetzorg Friesland. The Netherlands.
18. KDOO (2018) Database of dieans in the Netherlands who treat
paents with low carbohydrate diets.
19. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, et al. (2014) Eects
of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial. Ann
Intern Med 161: 309-318.
20. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, et al. (2008)
Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat
Diet. N Engl J Med 359: 229-241.
21. Westphal SA (2008) Obesity, abdominal obesity, and insulin
resistance. Clin Cornerstone 9: 23-29.
22. UMCG (2015) HbA1c-De Bepalingenwijzer. Lab values for DMT2.
23. Gibson AA, Seimon RV, Lee CM, Ayre J, Franklin J, et al. (2015) Do
ketogenic diets really suppress appete? A systemac review and
meta-analysis. Obes Rev 16: 64-76.
24. Ryan DH, Yockey SR (2017) Weight Loss and Improvement in
Comorbidity: Dierences at 5%, 10%, 15%, and Over. Curr Obes Rep
6: 187-194.
25. Avenell A, Brown TJ, McGee MA, Campbell MK, Grant AM, et al.
(2014) What are the long-term benets of weight reducing diets in
adults? A systemac review of randomized controlled trials. J Hum
Nutr Diet 17: 317-335.
26. Elhayany A, Lustman A, Abel R, Aal-Singer J, Vinker S (2010) A
low carbohydrate Mediterranean diet improves cardiovascular risk
factors and diabetes control among overweight paents with type
2 diabetes mellitus: a 1-year prospecve randomized intervenon
study. Diabetes Obes Metab 12: 204-219.
27. Snorgaard O, Poulsen GM, Andersen HK, Astrup A (2017) Systemac
review and meta-analysis of dietary carbohydrate restricon
in paents with type 2 diabetes. BMJ Open Diabetes Res Care 5:
e000354.
28. Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, et al. (2009) Inuence
of fat and carbohydrate proporons on the metabolic prole in
paents with type 2 diabetes: a meta-analysis. Diabetes Care 32:
959-965.
29. ME van Veen-Lievaart (2017) Richtlijn 5: Diabetes mellitus type 1 en
2 bij volwassenen Dieet behandelingsrichtlijnen Translaon: dietary
guidelines for DMT2.
30. Overbeek JA, Heintjes EM, Prieto-Alhambra D, Blin P, Lassalle R, et al.
(2017) Type 2 Diabetes Mellitus Treatment Paerns across Europe:
A Populaon-based Mul-database Study. Clin Ther 39: 759-770.
31. Dyson PA (2008) A review of low and reduced carbohydrate diets
and weight loss in type 2 diabetes. J Hum Nutr Diet 21: 530-538.
32. Westman EC, Mavropoulos J, Yancy WS, Volek JS (2003) A review of
low-carbohydrate ketogenic diets. Curr Atheroscler Rep 5: 476-483.
Sci Forschen
Open HUB for Sc ie n t i f i c R e s e a r c h
Citaon: Govers E, Oen A, Schuiling B, Bouwman W, Lourens A, et al. (2019) Eecveness of a Very Low Carbohydrate Ketogenic Diet
Compared to a Low Carbohydrate and Energy-Restricted Diet in Overweight/Obese Type 2 Diabetes Paents. Int J Endocrinol Metab
Disord 5(2): dx.doi.org/10.16966/2380-548X.158
10
Internaonal Journal of Endocrinology and Metabolic Disorders
Open Access Journal
33. Dash HM, Mathew TC, Khadada M, Al-Mousawi M, Talib H, et al.
(2007) Benecial eects of ketogenic diet in obese diabec subjects.
Mol Cell Biochem 302: 249-256.
34. Kirk JK, Graves DE, Craven TE, Lipkin EW, Ausn M, et al. (2008)
Restricted-carbohydrate diets in paents with type 2 diabetes: a
meta-analysis. J Am Diet Assoc 108: 91-100.
35. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, et
al. (2012) Management of hyperglycaemia in type 2 diabetes: a
paent-centered approach. Posion statement of the American
Diabetes Associaon (ADA) and the European Associaon for the
Study of Diabetes (EASD). Diabetes Care 55: 1364-1379.
36. Schultz JA, Sprague MA, Branen LJ, Lambeth S (2001) A comparison
of views of individuals with type 2 diabetes mellitus and diabetes
educators about barriers to diet and exercise. J Health Commun 6:
99-115.
37. ter Horst KW, Gilijamse PW, Koopman KE, de Weijer BA, Brands M, et
al. (2015) Insulin resistance in obesity can be reliably idened from
fasng plasma insulin. Int J Obes (Lond) 39: 1703-7109.
... An earlier study published in 2019 provided evidence on the beneficial effects of Medical Nutrition Therapy (MNT) through a very lowcarb/high-protein diet (6x6 ® ) on patients with severe insulin resistance and comorbidities [1]. Patients with T2DM were more successful in losing weight and remission of T2DM measured by Hba1c and the use of anti-diabetic drugs on a very low carbohydrate diet than on a more liberal carbohydrate intake or an energy restricted diabetic diet. ...
... Because weight loss is beneficial for restoring of one of the most important health factors, the low-grade inflammation, it is required to choose a dietary strategy that suppresses low grade inflammation. The optimal way to reach that goal is to choose any intervention which causes substantial weight loss [1,20,25,26]. ...
... This has been shown in several studies on clinical endpoints i.e. durable weight reduction as well as restoration of comorbidities, especially T2DM [26] and CVD [27]. Table 1 gives an outline of this typical form of MNT that reduces carbohydrate intake below 50 grams per day in the intensive phase, as is the case with the 6x6 diet, containing 36 grams per day in the first phase [1]. The 6 x 6 diet consists of three phases. ...
Research
Full-text available
Methods: We searched Pubmed, Medline and Google Scholar with the search terms: insulin resistance; obesity; overweight; weight loss; comorbidities; dietary treatment; low carb/high protein diet. And furthermore: fatty acids; omega 6-3 ratio; glycaemic index; glycaemic load and gut microbiome. Results: Weight loss suppresses IR and chronic inflammation in obese and overweight patients through the reduction of inflammation markers like CRP, IL-6 and TNF-α; and an increase in adiponectin, IL-10 and IL-1ra. Weight loss leads to reversed postprandial inflammatory expression. The very low-carb/high-protein diet (VLCKD) that suppresses low grade inflammation is characterized by: a carbohydrate intake below 50 g/day during six months or more; a protein intake of 1 g/present weight; an omega 6/3 ratio of 4/1; ample intake of fiber; and suppletion of micronutrients including vitamin D and iodine. Treatment is long lasting, after an intensive phase of one year and carried out by registered dietitians. Conclusion: Very low-carbohydrate/high-protein diets are effective for weight loss, to restore insulin sensitivity and reduce inflammation in patients with severe IR and comorbidities. Because of their complexity they should be administered by registered dietitians as part of Medical Nutrition Therapy.
... These effects have been described as pleasant since the patients feel they can control their appetite, which is new to them. Secondly, the high protein intake attained during the KD is associated with better muscle mass preservation, stimulating energy expenditure and causing more weight loss [22]. Some contradictory results have been presented in some of the included studies. ...
Article
Full-text available
Diabetes mellitus (DM) is a global epidemic causing significant morbidity and mortality. The most occurring DM is type 2 diabetes mellitus (T2DM) which has similar symptoms as type 1 diabetes mellitus (T1DM). However, it is less marked, making it difficult to diagnose during the early stages. The management of T2DM is usually based on weight and glycemic control, which can be achieved through dietary interventions such as intermittent fasting (IF) and the ketogenic diet (KD). Therefore, this systematic review and meta-analysis aim to demonstrate the role of IF and KD in glycemic and weight control among patients with T2DM. Two methods, including an electronic database search through ScienceDirect, Google Scholar, PubMed, Scopus, Embase, and Web of Science, and a manual search were used to identify relevant studies published between 2000 and 2022. The search yielded 1299 articles, of which only 12 met the inclusion criteria. In addition, study quality appraisal was performed using Review Manager software (RevMan 5.4.1). The pooled results have shown that IF had a similar effect on HBA1c reduction as control interventions (standardized mean differences [SMD]: 0.36%; 95% CI;-0.37, 1.10; P = 0.33, I2 = 87%). Similarly, an insignificant difference in weight reduction between IF and control interventions was recorded (SMD:-1.05%; 95% CI;-2.29, 0.19; P = 0.10, I2 = 96%). On the other hand, KD significantly reduced body weight compared with control diets (SMD:-1.91 kg; 95% CI;-2.96 kg,-0.85 kg; P = 0.0004, I2 = 96%). Similarly, KD had a better effect on the HBA1c percentage reduction than control diets (SMD:-2.00%; 95% CI;-3.76,-0.25; P = 0.03, I2 = 97%). IF and KD have shown reductions in HBA1c and body weight among patients with T2DM. However, the interventions are subject to side effects and should be used with caution and under the supervision of a health professional.
... These effects have been described as pleasant since the patients feel they can control their appetite, which is new to them. Secondly, the high protein intake attained during the KD is associated with better muscle mass preservation, stimulating energy expenditure and causing more weight loss [22]. Some contradictory results have been presented in some of the included studies. ...
Preprint
Full-text available
Diabetes mellitus (DM) is a global epidemic causing significant morbidity and mortality. The most occurring DM is type 2 diabetes mellitus (T2DM) which has similar symptoms as type 1 diabetes mellitus (T1DM). However, it is less marked, making it difficult to diagnose during the early stages. The management of T2DM is usually based on weight and glycemic control which can be achieved through dietary interventions such as intermittent fasting (IF) and the ketogenic diet (KD). Therefore, this systematic review and meta-analysis aim to demonstrate the role of IF and KD in glycemic and weight control among patients with T2DM. Two methods, including an electronic database search through ScienceDirect, Google Scholar, PubMed, Scopus, Embase, and Web of Science, and a manual search were used to identify relevant studies published between 2000 and 2022. The search yielded 1299 articles, of which only 12 met the inclusion criteria. Study quality appraisal was performed using Review Manager software (RevMan 5.4.1). The pooled results have shown that IF had similar effect on HBA1c reduction as control interventions (SMD: 0.36%; 95% CI;-0.37, 1.10; P = 0.33, I 2 = 87%). Similarly, an insignificant difference in weight reduction between IF and control interventions was recorded (SMD:-1.05%; 95% CI;-2.29, 0.19; P = 0.10, I 2 = 96%). On the other hand, KD significantly reduced body weight compared with control diets (SMD:-1.91kg; 95% CI;-2.96kg,-0.85kg; P = 0.0004, I 2 = 96%). Similarly, KD had a better effect on the HBA1c percentage reduction than control diets (SMD:-2.00%; 95% CI;-3.76,-0.25; P = 0.03, I 2 = 97%). IF and KD have shown reductions in HBA1c and body weight among patients with T2DM. However, the interventions are subject to side effects and should be used with caution and under the supervision of a health professional.
... Among them, the report from Dietary Intervention Randomized Controlled Trial (DIRECT) Group reported the actual efficacy of LCD for 2 years and 4 years with medical evidence [5,6]. There have been many reports suggesting the predominance of LCD rather than CR until now [7][8][9]. ...
Article
Full-text available
Diabetes has been a crucial medical and social problem worldwide. For adequate nutritional therapy, there have been discussions concerning Calorie Restriction (CR) and Low Carbohydrate Diet (LCD). We have investigated glucose variability of diabetic patients applying CR, LCD, continuous glucose monitoring (CGM) and applied FreeStyle Libre which is flash glucose monitoring (FGM). The patient is a 40-year-old female with type 2 diabetes mellitus (T2DM), who showed BMI 20.7, postprandial blood glucose 257 mg/dL. HbA1c 12.1%, Glycoalbumin 31.6% (11.6-16.4), serum C-peptide 2.0 ng/ml and unremarkable data of liver function, renal, lipids. She was provided the intervention of three stages, which are i) CR with 60% carbohydrate in Day 1-2, ii) LCD meal with 12% carbohydrate in Day 3-5; iii) LCD + Sodium-glucose cotransporter 2 (SGLT2) inhibitor (Ipragliflozin L-Proline 50mg) in Day 6-12. The glucose profile was measured by FreeStyle Libre Pro (Abbott) for 14 days. The daily profile of blood glucose was abruptly decreased on Day 6. Time percentage of satisfactory blood glucose 70-180 mg/dL (/24h) was 0%, 0%, 2%, 14%, 0%, 54%, 100% in Day 1-7, respectively. These results suppose the acute clinical efficacy of SGLT2 inhibitor, and this report would become a reference for future diabetic practice and research.
Article
Full-text available
Introduction and Rationale: Low carbohydrate high protein diets have been prescribed from as early as 1797 and are taken seriously by many researchers, although in main stream dietetics and medicine the diet can still be received with skepticism. Insulin resistance (IR) is the result of a cascade of physiological events, starting with hyperphagia leading to a positive energy balance and weight gain. Patients with IR gain weight easily and have trouble losing weight on diets with normal carbohydrate content, because of the highly elevated insulin levels. A diet for patients with IR must therefore tackle this problem to make weight loss possible. In this review the evidence on the diet short and long-term, effects on comorbidities and difference with Mediterranean diet are discussed. Methods: A search was carried out in Pubmed for articles of obesity management, IR, low carb/high protein diets and weight loss combined with comorbidities, several nutrients and the Mediterranean diet between 1995 and July 2017. Outcomes were compared to patient observations from dietary practice in weight loss management. Management: Diagnosis can easily be made by measuring waist circumference. The diet should be low carb/high protein but not provoking ketosis; energy and macro nutrient requirements should be individually assessed. Fat is not low but also not ad libitum, focusing on unsaturated fats. The intake of vitamin D, iodine and magnesium needs to be optimal. Alcohol consumption is not part of first phase of the diet. Exercise (endurance and resistance) is an essential part of the therapy. For patients with type 2 diabetes medication, diet and glucose values need to be meticulously observed. Conclusion: Low carbohydrate/high protein diets should be considered as a serious treatment option for all obese patients with and without comorbidities. They should be administered by specialised dietitians working in a multi-disciplinary team. Keywords: Low carbohydrate/high protein diet; Insulin resistance; Obesity; T2dm; Cvd; Nafld; Dietitian
Article
Full-text available
Purpose of review: One begins to see improvement in glycemic measures and triglycerides with small amounts of weight loss, but with greater levels of weight loss there is even greater improvement. In fact, the relationship between weight loss and glycemia is one that is very close. Recent findings: This is fortunate for diabetes prevention; it takes only small amounts of weight loss to prevent progression to type 2 diabetes from impaired glucose tolerance, and after the 10 kg of weight loss, one cannot demonstrate much additional improvement in risk reduction. Modest weight loss (5 to 10%) is also associated with improvement in systolic and diastolic blood pressure and HDL cholesterol. With all these risk factors, more weight loss produces more improvement. Further, for patients with higher BMI levels (>40 kg/m(2)), the ability to lose the same proportion of weight with lifestyle intervention is equal to that of those with lower BMI levels, and there is equal benefit in terms of risk factor improvement with modest weight loss. For some comorbid conditions, more weight loss is needed-10 to 15%-to translate into clinical improvement. This is true with obstructive sleep apnea and non-alcoholic steatotic hepatitis. There is a graded improvement in improvements in measures of quality of life, depression, mobility, sexual dysfunction, and urinary stress incontinence, whereby improvements are demonstrable with modest weight loss (5-10%) and with further weight loss there are further improvements. For polycystic ovarian syndrome and infertility, modest weight loss (beginning at 2-5%) can bring improvements in menstrual irregularities and fertility. Moderate weight loss (5-10%) has been shown to be associated with reduced health care costs. Reduction in mortality may take more than 10% weight loss, although definitive studies have not been done to demonstrate that weight loss per se is associated with mortality reduction. Clinicians in medical weight management should bear in mind that the target should be health improvement rather than a number on the scale. The individual patient's targeted health goal should be assessed for response rather than a prescribed percentage weight loss.
Article
Full-text available
Objective Nutrition therapy is an integral part of self-management education in patients with type 2 diabetes. Carbohydrates with a low glycemic index are recommended, but the ideal amount of carbohydrate in the diet is unclear. We performed a meta-analysis comparing diets containing low to moderate amounts of carbohydrate (LCD) (energy percentage below 45%) to diets containing high amounts of carbohydrate (HCD) in subjects with type 2 diabetes. Research design and methods We systematically reviewed Cochrane library databases, EMBASE, and MEDLINE in the period 2004–2014 for guidelines, meta-analyses, and randomized trials assessing the outcomes HbA1c, BMI, weight, LDL cholesterol, quality of life (QoL), and attrition. Results We identified 10 randomized trials comprising 1376 participants in total. In the first year of intervention, LCD was followed by a 0.34% lower HbA1c (3.7 mmol/mol) compared with HCD (95% CI 0.06 (0.7 mmol/mol), 0.63 (6.9 mmol/mol)). The greater the carbohydrate restriction, the greater the glucose-lowering effect (R=−0.85, p<0.01). At 1 year or later, however, HbA1c was similar in the 2 diet groups. The effect of the 2 types of diet on BMI/body weight, LDL cholesterol, QoL, and attrition rate was similar throughout interventions. Limitations Glucose-lowering medication, the nutrition therapy, the amount of carbohydrate in the diet, glycemic index, fat and protein intake, baseline HbA1c, and adherence to the prescribed diets could all have affected the outcomes. Conclusions Low to moderate carbohydrate diets have greater effect on glycemic control in type 2 diabetes compared with high-carbohydrate diets in the first year of intervention. The greater the carbohydrate restriction, the greater glucose lowering, a relationship that has not been demonstrated earlier. Apart from this lowering of HbA1c over the short term, there is no superiority of low-carbohydrate diets in terms of glycemic control, weight, or LDL cholesterol.
Article
Full-text available
BACKGROUND/OBJECTIVES: Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to 1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps, 2) identify insulin-resistant obese subjects and 3) predict insulin resistance from routinely measured variables. SUBJECTS/METHODS: We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step euglycemic hyperinsulinemic clamps using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2)·min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. RESULTS: Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-1)·min(-1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd <37.3 μmol kg(-1)·min(-1) did not differ from insulin-sensitive obese men in age, BMI, body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol/l, P<0.001) and HOMA-IR (4.5±2.2 vs 2.7±1.4, P=0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol/l. CONCLUSIONS: Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, i.e. insulin resistance. Fasting insulin (>74 pmol/l with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings. International Journal of Obesity accepted article preview online, 09 July 2015. doi:10.1038/ijo.2015.125.
Article
Nutrition therapy is considered a key component of diabetes management, yet evidence around the ideal macronutrient composition of the diet remains inconclusive. A systematic review and meta-analysis was performed to assess the effects of carbohydrate-restricted diets (≤ 45% of total energy) compared to high carbohydrate diets (> 45% of total energy) on glycemic control in adults with diabetes mellitus. Six databases were searched for articles published between January 1980 and August 2016. Primary outcome was between-group difference in HbA1c change. Individual effect sizes were standardized, and a meta-analysis performed to calculate pooled effect size using random effects. 25 RCTs involving 2412 participants were included. Carbohydrate-restricted diets, in particular those that restrict carbohydrate to < 26% of total energy, produced greater reductions in HbA1c at 3 months (WMD -0.47%, 95% CI: -0.71, -0.23) and 6 months (WMD -0.36%, 95% CI: -0.62, -0.09), with no significant difference at 12 or 24 months. There was no difference between moderately restricted (26-45% of total energy) and high carbohydrate diets at any time point. Although there are issues with the quality of the evidence, this review suggests that carbohydrate-restricted diets could be offered to people living with diabetes as part of an individualised management plan.
Article
Purpose: The aim of this study was to determine the similarities and differences of type 2 diabetes mellitus (T2DM) treatment patterns in daily practice in 5 European countries and whether these reflect differences in guidelines. Methods: Prescriptions for drugs used in diabetes treatment during a 5-year study period were obtained from electronic databases. Patients initiating T2DM treatment during the study period were included. An SAS analysis tool was developed to create episodes of use of drug classes, which resulted in treatment patterns. Findings: A total of 253,530 patients initiating T2DM treatment during the study period were included; 52% to 55% were male, and the mean age ranged from 62 to 67 years. Metformin was the most common initial treatment in all countries. After initial therapy, most patients in the Netherlands, Spain, and the United Kingdom switched to a combination of metformin + a sulfonylurea derivative (SU). In Italy, metformin in combination with an SU was outnumbered by "other treatment," mainly because of repaglinide use. In France, treatments including dipeptidyl peptidase-4 inhibitors were most frequent as second- and fourth-line treatment. Metformin monotherapy was again most commonly observed as the third line of treatment in all countries. Fourth treatment was a combination of metformin + an SU in the Netherlands and Spain; in the United Kingdom and France, dipeptidyl peptidase-4 inhibitors were the most frequently used fourth line of treatment. Implications: This study provides a comprehensive overview of T2DM treatment patterns among patients initiating T2DM treatment in 5 European countries. There were differences, especially regarding the uptake of newer incretin-based treatments, which are usually prescribed as a second and/or third treatment in agreement with local guidelines. These variations reflect the differences between the national guidelines of these countries.
Article
Very-low-energy diets (VLEDs) and ketogenic low-carbohydrate diets (KLCDs) are two dietary strategies that have been associated with a suppression of appetite. However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent. To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, we conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analogue scales before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD. Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat. Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people. Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied). Ketosis appears to provide a plausible explanation for this suppression of appetite. Future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.
Article
BACKGROUND: Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations. OBJECTIVE: To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors. DESIGN: A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271). SETTING: A large academic medical center. PARTICIPANTS: 148 men and women without clinical cardiovascular disease and diabetes. INTERVENTION: A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial. MEASUREMENTS: Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months. RESULTS: Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet. LIMITATION: Lack of clinical cardiovascular disease end points. CONCLUSION: The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors.