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A review of recent evidence relating to sugars, insulin resistance and diabetes

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Abstract

The potential impact on health of diets rich in free sugars, and particularly fructose, is of major concern. The focus of this review is the impact of these sugars on insulin resistance and obesity, and the associated risk of developing type 2 diabetes. Much of the concern is focussed on specific metabolic effects of fructose, which are argued to lead to increased fat deposition in the liver and skeletal muscle with subsequent insulin resistance and increased risk of diabetes. However, much of the evidence underpinning these arguments is based on animal studies involving very large intakes of the free sugars. Recent human studies, in the past 5 years, provide a rather different picture, with a clear dose response link between fructose intake and metabolic changes. In particular, the most marked effects are observed when a high sugars intake is accompanied by an excess energy intake. This does not mean that a high intake of free sugars does not have any detrimental impact on health, but rather that such an effect seems more likely to be a result of the high sugars intake increasing the chances of an excessive energy intake rather than it leading to a direct detrimental effect on metabolism.
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DOI 10.1007/s00394-016-1340-8
REVIEW
A review of recent evidence relating to sugars, insulin resistance
and diabetes
I. A. Macdonald1
Received: 23 March 2016 / Accepted: 23 October 2016 / Published online: 23 November 2016
© The Author(s) 2016. This article is published with open access at Springerlink.com
Introduction
There is increasing interest in the possibility that a high
intake of refined sugars is associated with detrimental
effects on metabolism that increase the risk of cardiovas-
cular disease, obesity, insulin resistance and diabetes. Some
of the evidence underpinning these concerns is derived
from cross-sectional surveys or ecological observations,
but there are also prospective cohort studies and controlled
intervention trials which have addressed this issue. This
brief narrative review arises from a Symposium on Sugars
and Health held at the European Nutrition Conference in
October 2015. It will consider the recent work, published in
the past 5 years, which has focussed on the potential impact
of dietary sugars on health, in particular insulin resistance
and diabetes risk, and seeks to identify the intakes which
might be associated with health-related problems. The
terminology employed in these discussions is often used
rather loosely, with the term ‘sugar’ often being used to
represent a range of different molecules. For the purposes
of this article, ‘sugar’ is taken to be the common term for
sucrose, and the collective term ‘sugars’ will be used to
include sucrose, glucose and fructose together with the
high fructose corn syrups which are replacing sucrose in
sweetened beverages and foods in many countries.
Basic aspects of dietary carbohydrates, insulin
action and insulin resistance
Dietary carbohydrates include the monosaccharides, disac-
charides, oligosaccharides (chain length 3–9 molecules),
polysaccharides and fibre. The monosaccharides are glu-
cose, fructose and galactose, and the major disaccharides
are sucrose (glucose plus fructose), lactose (glucose and
Abstract The potential impact on health of diets rich
in free sugars, and particularly fructose, is of major con-
cern. The focus of this review is the impact of these sug-
ars on insulin resistance and obesity, and the associated
risk of developing type 2 diabetes. Much of the concern is
focussed on specific metabolic effects of fructose, which
are argued to lead to increased fat deposition in the liver
and skeletal muscle with subsequent insulin resistance and
increased risk of diabetes. However, much of the evidence
underpinning these arguments is based on animal stud-
ies involving very large intakes of the free sugars. Recent
human studies, in the past 5 years, provide a rather differ-
ent picture, with a clear dose response link between fruc-
tose intake and metabolic changes. In particular, the most
marked effects are observed when a high sugars intake is
accompanied by an excess energy intake. This does not
mean that a high intake of free sugars does not have any
detrimental impact on health, but rather that such an effect
seems more likely to be a result of the high sugars intake
increasing the chances of an excessive energy intake rather
than it leading to a direct detrimental effect on metabolism.
Keywords Sugars · Sucrose · Fructose · Glucose · HFCS ·
Insulin resistance · Diabetes mellitus
This article belongs to a supplement sponsored by Rippe Health.
* I. A. Macdonald
ian.macdonald@nottingham.ac.uk
1 Queen’s Medical Centre, School of Life Sciences, University
of Nottingham Medical School, University of Nottingham,
Clifton Boulevard, Nottingham NG7 2UH, UK
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galactose) and maltose (2 glucose molecules). The polysac-
charide category represents the starches, which are made
up of glucose polymers with variation in the location and
number of cross-linkages between the molecules producing
different sub-categories of starches. The mono- and disac-
charides are normally combined into the collective category
of sugars. The main carbohydrate contributors to dietary
energy intake are the sugars and starches. The control of
carbohydrate metabolism is dependent on appropriate lev-
els of insulin secretion and insulin action. For the purposes
of the present overview, the issues around insulin secretion
(particularly as it relates to type 2 DM) will not be consid-
ered. However, the impact of dietary carbohydrates or total
energy intake on insulin action is worthy of consideration.
Whilst there is currently some controversy over the role
of carbohydrates in a healthy diet, most if not all national
guidelines recommend that the proportion of energy con-
tributed by carbohydrate should be approximately 50%
(e.g. [1]). It has been known for at least 80 years that a low
carbohydrate/high fat intake is associated with poorer glu-
cose tolerance and insulin resistance [2]. The major con-
cern at present is focussed on dietary sugars, and whether
an excessive intake of them as a proportion of total car-
bohydrate can lead to insulin resistance and impaired glu-
cose tolerance and lead to an increased risk of developing
type 2 diabetes mellitus (DM). There is increasing concern
about the potential threat to health represented by a high
intake of sugars, as evidenced by the recent Dietary Guide-
lines for Americans [3], UK Scientific Advisory Commit-
tee for Nutrition’s Carbohydrate report [1] and the WHO
Sugars Report [4]. Although most of the attention has been
focussed on sucrose and fructose, many studies have failed
to directly compare fructose and glucose in randomised
trials, and when direct comparisons have been made, it is
clear that any impact on health is more likely to be a sugars-
related effect than specifically due to fructose (see later).
This short review will consider this issue in greater detail
and assess the potential problems of sugars in relation to
insulin resistance and risk of type 2 DM. The present arti-
cle is a narrative review based on the systematic reviews
undertaken to inform the SACN Review of Carbohydrates
and Health. The details of these 3 systematic reviews are
provided in the SACN report, including the search strate-
gies and the inclusion/exclusion criteria. The additional lit-
erature included in the present review was identified sepa-
rately from this systematic review process, and this was not
performed using systematic review criteria but was simply
designed to illustrate some of the additional aspects of this
field and the more recent observations reported in the past
5 years. One of the major issues in this area of research is
the short-term nature of many of the investigations, espe-
cially studies involving alteration of the carbohydrate com-
position of the diet or the types of sugars being consumed.
Clearly the long-term health effects of such interventions
can only be speculated about, but such studies do provide
useful information on potential mechanisms of effects of
carbohydrates on health.
What are the major issues relating to dietary
fructose? Contrast between research evidence
and speculation/opinion
There has been concern expressed for many years that
sucrose, and particularly fructose, represent potential prob-
lems as far as risks to health are concerned. One of the
first major critics of sucrose in the diet was John Yudkin
[5], whose book ‘Pure, white and deadly’ summarised the
scientific information available in the 1960s/early 1970s
and promoted his opinion conveyed in the book’s title
that diabetes, cardiovascular disease and other chronic ill-
nesses were contributed to by a high sucrose intake. In
more recent times, these views have resurfaced and been
extended to include the high fructose corn syrup (HFCS)
content of foods and drinks. These opinions relating to the
threat to health from fructose alone and as a component of
sucrose and HFCS, are sustained despite reports such as
that from the German Nutrition Society, which concluded
that intakes of up to 100 g fructose per day are not asso-
ciated with increased serum triglycerides and that fructose
and sucrose are not associated with increased risk of hyper-
tension or CHD [6].
The principal concern raised in relation to fructose is
that its metabolism promotes lipid synthesis in the liver and
because it is metabolised independently of insulin action in
the liver and elsewhere, it can lead to excessive lipid forma-
tion and deposition, insulin resistance and other features of
the metabolic syndrome. However, the studies which have
investigated potential effects of fructose on liver fat con-
tent, plasma lipids or insulin sensitivity have often failed
to include a glucose control treatment, and thus any effect
ascribed to fructose may simply be an effect of monosac-
charides (see below). Longitudinal cohort studies and eco-
logical observations have been used to associate increased
obesity with high levels of sucrose, fructose or HFCS
consumption. For example, Fiorito et al. [7] reported that
higher sweetened beverage intake in 5-year-old girls was
associated with increased BMI and adiposity 10 years later,
whilst Nissinen et al. [8] in the young Finns study reported
an association between increasing sugar-sweetened bever-
age intake from childhood to adulthood was associated
with increased adult BMI in women. However, such obser-
vations can at best signal a concern that then needs investi-
gating in controlled trials.
In some cases, the arguments for an increased risk to
health associated with high intake of fructose arise from
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reviews of experimental animal studies combined with
human ecological observations. An example of this is pro-
vided by Johnson et al. [9] who reviewed studies in meta-
bolic syndrome prone rats that developed fatty livers whilst
receiving 40% of their dietary energy from sucrose. This
review also attributed to Lustig and colleagues [10], show-
ing an epidemiological association of increased diabetes
prevalence with increased sugar availability. However, this
was a population level econometric analysis based on mul-
tiple cross-sectional observations. It is rather speculative
and undesirable to draw major conclusions of causation or
association from such a combination of econometric and
animal data.
There is evidence from other animal experiments of
effects of sucrose or fructose plus glucose on insulin
resistance, liver fat content and liver levels of inflamma-
tory markers [11]. However, these rats received 60% of
their total energy intake as sucrose, or 30% as fructose
and 30% as glucose. Both of these dietary treatments are
so extreme; it is not surprising that metabolic abnormali-
ties were observed. Another study fed mice with a diet pro-
viding 38.5% of energy as sucrose and observed elevated
plasma glucose levels in the early phase of an oral glucose
tolerance test (OGTT) indicative of insulin resistance or
impaired insulin release [12]. However, the same study
showed that sucrose feeding improved insulin sensitivity
as assessed during an insulin tolerance test. One possible
explanation of these apparently opposing observations is
that high levels of sucrose feeding to these mice may have
led to a reduction in the release of one or more of the incre-
tin hormones from the GI tract during food/glucose inges-
tion, reducing the insulin response to the OGTT and thus
leading to higher plasma glucose levels.
What is the evidence from randomised controlled
trials (RCT) of the metabolic effects of fructose or
sucrose?
Some reviews and commentaries have urged caution in
attributing major health risks associated with fructose/
sucrose in people. Klurfeld et al. [13] assessed the potential
link between HFCS and obesity and concluded that the evi-
dence was not supportive of such a claim and commented
that RCT at levels even exceeding normal human consump-
tion have also been inconclusive related to fructose, sucrose
and obesity. A subsequent review by Tappy and Mitten-
dorfer [14] commented that whilst some studies describe
potential adverse effects of high fructose intakes, particu-
larly as part of an excessive energy intake, there does not
appear to be a significant detrimental effect of fructose
when part of a weight-maintaining diet. They concluded
by commenting that definitive studies were missing. Since
then, a number of RCT have been published which shed
further light on this issue.
Bravo et al. [15] performed a study in healthy, over-
weight adults which involved providing sweetened low-
fat milk which contained 8, 18 or 30% of estimated daily
energy requirements in the form of sucrose or HFCS, for
a period of 10 weeks. There was an increase in reported
energy intake over the course of the study when all groups
were combined, and whilst the groups receiving 18 and
30% of energy from the sugars appeared to have the most
marked increases, there were no significant increases in any
group. There was an increase in body weight across the
study, although this was only significant in the 30% sugars
groups with mean increases of 1 and 2.3 kg over 10 weeks
in the 30% sucrose and the 30% HFCS groups. Despite the
increase in body weight, there were no significant changes
in the fat content of the liver or skeletal muscles in any
group. When data for all groups were combined, there was
a significant increase in plasma triglycerides (from 1.11 to
1.27 mmol/l), but there were no differences between the
groups and no significant change within any individual
group (presumably due to a lack of statistical power). There
were no changes in plasma cholesterol during the study.
Heden et al. [16] also found no effect of moderate daily
intakes of mixtures of fructose and glucose for a period of
2 weeks in physically active adolescents. They consumed
mixtures containing 50 g fructose and 15 g glucose, or 15 g
fructose and 50 g glucose, daily for 2 separate 2-week peri-
ods. When these supplements were considered together
with the dietary fructose and glucose, the total intakes were
around 70 g fructose and 40 g glucose, compared to 40 g
fructose and 70 g glucose. The combined sugars intakes
equated to approximately 25% of total energy intake. There
were no significant changes in fasting and postprandial
indices of insulin resistance, or fasting blood lipids with
either treatment, or any difference in response between
subjects who were overweight compared to the healthy
weight subjects.
An interesting study by Aeberli et al. [17] assessed the
effect of different amounts of fructose or glucose supple-
mentation in a beverage, on insulin sensitivity using the
glucose clamp technique. Intriguingly, the title of the paper
is ‘Moderate Amounts of Fructose Consumption Impair
Insulin Sensitivity in Healthy Young Men’, but the results
obtained show that the only change in insulin sensitivity
was a reduction in the degree of insulin-induced suppres-
sion of hepatic glucose production after the high fructose
drink (80 g/day for 3 weeks) intake compared with the 80 g
glucose drink. There were no differences in whole body,
systemic insulin sensitivity and no differences between
the groups in fasting insulin and glucose concentrations.
Furthermore, there was no difference in any component of
insulin sensitivity between the moderate fructose (40 g/day)
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drink or 80 g sucrose drink and the 80 g glucose control
drink. This suggests a threshold intake of fructose is needed
for an effect on hepatic insulin resistance. The total fructose
intake after the 40 g drink was 77 g/day, whilst the total
fructose intake after the 80 g drink was 115 g/day. Thus,
from this study the threshold appears to be somewhere
between fructose intakes equivalent to 15 and 23% of total
energy intake. It is interesting to note that there did not
appear to be any impact of these sugars containing drinks
on total energy intake compared to the baseline condi-
tion, with some compensatory reductions in protein and fat
intake balancing the additional energy from sugars. Such
compensation has not been reported in other studies involv-
ing increased intake of sugars containing drinks. There was
also no effect on fasting serum triglycerides which is sur-
prising as other studies have shown an increased monosac-
charide intake leads to a rise in triglycerides.
An interesting contrast to the Aeberli study is found in the
work of Hokayem et al. [18] who studied insulin resistance
in relatives of people with type 2 DM. Because of their fam-
ily history, such people have an increased risk of developing
diabetes and are likely to be insulin resistant. The purpose of
this study was to examine the effects of grape polyphenols
on the metabolic consequences of short-term consumption
of a high fructose intake (3 g fructose/kg fat free mass per
day for 6 days). The fructose intake was designed to induce
insulin resistance and oxidative stress. The group consuming
the grape polyphenols did not show any reduction in glucose
infusion rate during the glucose clamp or any change in the
fasting insulin sensitivity index after 6 days of fructose con-
sumption. By comparison, the placebo control group had an
11% reduction in glucose infusion rate and a 19% reduction
in the fasting insulin sensitivity index.
Stanhope et al. [19] provided obese subjects with
25% of their energy requirements as glucose or fructose
for 10 weeks. Both groups had similar increases in body
weight (+1.8% in the glucose and +1.4% in the fructose
groups) and body fat content (+3.2 and +2.8%), indicating
that this was essentially an overfed state. Only the fructose
group showed an increase in postprandial serum triglyc-
erides (TG) from late afternoon onwards, with no change
in fasting TG in either group. There was also evidence of
impaired glucose tolerance with increased insulin responses
in the fructose group, with no change in the glucose group.
However, the oral glucose load in the glucose tolerance
test is not something that the fructose group would have
been used over the previous weeks, and so without glucose
clamp-based assessments of insulin resistance, it is difficult
to interpret the glucose tolerance data.
Lecoultre et al. [20] reported a study of the effects of fruc-
tose, glucose or fat overfeeding for 6 days on hepatic insulin
sensitivity and intrahepatic lipids in healthy people. Three
different doses of fructose were investigated, 1.5, 3 and 4 g
per kg body weight per day, which were additional to the
diet required to maintain weight. This equated to an excess
energy intake of 17, 32 and 43% of energy requirements. The
glucose dose used was 3 g/kg/day (37% overfeeding), and
the fat overfeeding was at a level of 30% of energy require-
ments. The 3 and 4 g doses of fructose, the glucose and the
fat overfeeding all increased liver fat content by 50 to 110%,
with the 3 g fructose dose having a significantly larger effect
that the 3 g glucose. Interestingly, the smaller degree of over-
feeding with 1.5 g fructose did not increase liver fat content.
The two higher doses of fructose (but not 1.5 g fructose or
the glucose or fat overfeeding) also reduced the hepatic insu-
lin sensitivity by about 20%. Thus, high fructose intakes dur-
ing overfeeding did increase liver fat and produce liver insu-
lin resistance, but 100 g of fructose per day (the lowest dose)
with modest overfeeding did not have such effects.
Stanhope et al. [21] recently reported a study of the
effects of varying amounts of high fructose corn syrup
(HFCS) consumed for 2 weeks, with the lowest amount
being equivalent to 10% of energy requirements. This low-
est quantity represents approximately 5% of total energy
from fructose and was not associated with any change in
body weight over the 2 weeks, whilst the 17.5 and 25%
HFCS groups did have an increase in weight. The 17.5 and
25% doses of HFCS were accompanied by increases in
postprandial TG, and the 25% dose also tended to increase
fasting TG. Interestingly, the 10% HFCS treatment also
increased postprandial TG in the late evening, indicat-
ing that this effect is not dependent on an increase in body
weight. No data were presented on glucose and insulin,
so it is not possible to comment on any effects on insulin
resistance of this low dose of HFCS.
The overall conclusion from these studies is that a fructose
intake exceeding 150 g/day in adults reduces fasting insulin
sensitivity but intakes appear to need to exceed 250 g/day
before affecting insulin-induced suppression of liver glucose
output. There is less clarity of potential effects on peripheral
insulin sensitivity, even at high fructose intakes. The higher
doses of fructose also appear to increase serum TG, in at least
some studies, and it is possible that this can occur with low
doses of fructose in so far as late evening postprandial TG
are concerned and without an increase in body weight (i.e.
without overfeeding). It is striking that the majority of these
observations are linked to situations where high fructose
intakes are accompanied by excessive energy intakes, and the
following section considers this in more detail.
Is the effect of fructose or sucrose affected by the
amount consumed or the total energy intake?
A study of ours directly compared high levels of glucose
or fructose intake in overweight, large-waisted men who
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were otherwise healthy [22]. The participants were stud-
ied in two separate 2-week periods, the first when fed at
energy balance (isoenergetic), with glucose or fructose pro-
viding 25% of total energy intake, and the second, at least
6 weeks later, when the sugars were added to their ad libi-
tum diet (with a target of 25% overfeeding). The men had
high initial levels of liver (8%) fat and intramuscular (8%)
fat at baseline, but there were no significant changes in
either the fructose or glucose groups when an isoenergetic
diet was provided. There was an increase in fasting insulin
resistance in the fructose group (HOMA-IR increased from
3.6 to 4.3) but not the glucose group (3.2 to 3.4), but there
were no significant changes in the suppression of hepatic
glucose output or peripheral insulin sensitivity during a
glucose clamp in either group. By contrast, when the same
subjects were overfed, there were increases in liver fat con-
tent to approximately 10% in both the fructose and glucose
groups, together with a trend for an increase in muscle fat of
a similar amount. With this fructose or glucose overfeeding,
there were no changes in HOMA-IR, and also no signifi-
cant changes in suppression of hepatic glucose production
or peripheral insulin sensitivity during the glucose clamp,
although there was a trend for a reduction in the latter which
was more noticeable in the glucose-treated group. The mean
doses of fructose or glucose provided in this study were
around 210 g/day, which is consistent with the previous sec-
tion in which it was suggested that fructose intakes need to
exceed 150 g/day before potentially deleterious effects are
observed. The other conclusions from this study are that
in overweight men with an elevated liver fat content, these
effects are similar for fructose and glucose and are predomi-
nantly linked to overfeeding than the sugars per se [22].
This link between excessive energy intake and deleteri-
ous effects of sugars is also illustrated by the review by Te
Morenga et al. [23], which formed part of the basis for the
WHO Sugars and Health report [4]. This systematic review
clearly showed that higher sugars intakes were linked to
increased body weight or fatness if ad libitum diets were
considered, but if sugars were exchanged for other carbo-
hydrates and energy intake was maintained constant, then
there were no deleterious effects of sugars.
A similar conclusion arose from the SACN Carbohy-
drates and Health Report [1], with higher sugars intake
in an ad libitum situation being associated with higher
energy intake. This report provided a meta-analysis of the
link between change in sugars intake and change in energy
intake in ad libitum intake in randomised controlled trials
which showed that the higher sugars intake (with a mean
increase of 10%) was associated with an increased energy
intake of approximately 1 MJ/day. Whether this repre-
sents an increased risk of developing type 2 DM, or just an
increased risk of weight gain and eventually obesity, cannot
be determined from these short-term RCT.
It is interesting to note that the SACN report also looked
at cohort studies examining associations between sugars
intake and incidence of type 2 DM. Whilst the studies iden-
tified had too much heterogeneity to allow a meta-analysis
to be performed, it was notable that they provided no con-
sistent evidence of an association between diets differing in
the proportion of sugars and the incidence of type 2 diabe-
tes mellitus.
A balanced overview of the current position regarding
potential health problems arising from fructose/sucrose
was provided by van Buul et al. [24]. They concluded that
fructose as normally consumed in foods does not exert spe-
cific metabolic effects that would contribute to weight gain.
They also concluded that the specific problems which have
been identified in relation to sugars-sweetened beverages
and risk of obesity are a result of energy overconsump-
tion rather than any effect of fructose on energy metabo-
lism or storage. However, it is clear that limiting sugars
intake as part of a strategy to limit energy intake whilst
at the same time increasing physical activity to increase
energy expenditure, represent the lifestyle changes needed
to address the current obesity problem in many countries.
Clearly, the recent observation of potential effects of mod-
est amounts of HFCS on postprandial TG, without associ-
ated weight gain, needs to be recognised [21]. However, it
is worth noting that the 10% HFCS that was consumed is
double the recommended intake of 5% of energy from free
sugars which was concluded in the SACN report.
Should we be more concerned about dietary
glycaemic characteristics than the sugars content?
There is increasing interest in the possibility that the gly-
caemic characteristics of carbohydrates may also be of
importance in relation to optimal health. The original con-
cept of glycaemic index was developed to help people with
diabetes to improve their glucose control. In recent times,
it has gained a wider application, and assessing the glycae-
mic index and glycaemic load of diets has been included
in a number of prospective cohort studies which are sum-
marised in the SACN report [1]. This has led to several
randomised controlled trials of potential benefits of lower
glycaemic index diets, including a recent study of our
own (Bawden et al. [25]) which showed that healthy non-
obese young men consuming a high glycaemic index diet
for 7 days showed an increase in liver fat content, whereas
7 days on a low glycaemic index diet was accompanied
by a small decrease in liver fat. In this study, the dietary
GI was estimated on the basis of the GI tables provided
by Brand-Miller’s group [26]. Further work is needed to
identify the potential impact of such differences on insulin
resistance.
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The SACN report [1] concluded that lower glycaemic
index diets were associated with reduced risk of cardiovas-
cular disease, but it is noticeable that most of the studies
included in this meta-analysis also appeared in the analysis
of associations with fibre intake, and clearly further work
is needed to establish whether the glycaemic characteristics
or some features of the fibre content are responsible for the
potential health benefits. Care must also be taken in pro-
moting low glycaemic index per se, because the glycaemic
index of fructose is very low and increasing the fructose
content would reduce a food’s glycaemic index.
Conclusions
There is an association between diets high in sugars (pre-
dominantly sucrose) and risk of disease, and experimen-
tal studies have shown that high intakes of fructose (over
100 g/d) can reduce insulin sensitivity, although somewhat
lower intakes may affect serum TG. The mechanisms for
such associations or effects have not been convincingly
demonstrated. However, it remains to be seen whether it
will be possible to unravel these mechanisms in the cur-
rent climate in which marked decreases in sucrose/fructose
intakes are being promoted as key public health strategies.
Overconsumption of fructose, as a contributor to an
excessive energy intake is linked with increased liver and
muscle fat contents, but a similar effect is seen with glu-
cose and thus it may be more linked to carbohydrate per se,
or possibly just to energy, overconsumption. Future work
with overfeeding of fat is needed to explore this further.
Compliance with ethical standards
Conflict of interest Ian Macdonald is a member of the UK Gov-
ernment Scientific Advisory Committee on Nutrition and Chaired its
recent Carbohydrates and Health Working Group, Treasurer of the Fed-
eration of European Nutrition Societies, Treasurer of the World Obe-
sity Federation, a member of the Mars Scientific Advisory Council,
the Mars Europe Nutrition Advisory Board, Scientific Adviser to the
Waltham Centre for Pet Nutrition and has a UK Government Research
Grant (from Innovate UK) for a project which is led by Mars UK. He
is also the Academic lead for the University of Nottingham’s strategic
research partnership with Unilever, advises the Nestle Research Center
on Nutrition and Health across the lifecycle, is on the Diet and Health
Advisory Board of IKEA, and is co-chair of the Carbohydrates Task
Force for ILSI Europe.
Open Access This article is distributed under the terms of the Crea-
tive Commons Attribution 4.0 International License (http://crea-
tivecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
made.
References
1. SACN Carbohydrates and Health Report (2015) Published for
public health England under licence from the Controller of Her
Majesty’s Stationery Office. ISBN: 978 0 11 708284 7
2. Himsworth HP (1935) The dietetic factor determining the glu-
cose tolerance and sensitivity to insulin of healthy men. Clin Sci
2:67–94
3. USDA (2015) Scientific Report of the 2015 Dietary Guidelines
Advisory Committee
4. WHO (2015) Guideline: sugars intake for adults and children.
WHO. ISBN: 978 92 4 154902 8
5. Yudkin J (1972) Pure, white and deadly: the new facts about
the sugar you eat as a cause of heart disease, diabetes and other
killers. Davis-Poynter Limited. SBN 0706700562, ISBN13:
9780706700565
6. Hauner H, Bechthold A, Boeing H, Brönstrup A, Buyken A, Les-
chik-Bonnet E, Linseisen J, Schulze M, Strohm D, Wolfram G
(2012) Evidence-based guideline of the german nutrition society:
carbohydrate intake and prevention of nutrition-related diseases.
Ann Nutr Metab 60(suppl 1):1–58
7. Fiorito LM, Marini M, Francis LA, Smiciklas-Wright H, Birch
LL (2009) Beverage intake of girls at age 5 y predicts adiposity
and weight status in childhood and adolescence. Am J Clin Nutr
90:935–942
8. Nissinen K, Mikkila V, Mannisto S, Lahti-Koski M, Rasanen L,
Viikari J, Raitakari O (2009) Sweets and sugar-sweetened soft
drink intake in childhood in relation to adult BMI and over-
weight. The cardiovascular risk in young finns study. Public
Health Nutr 12:2018–2020
9. Johnson RJ, Nakagawa T, Sanchez-Lozada G, Shafiu M, Sunda-
ram S, Le M, Ishimoto T, Sautin YY, Lanaspa MA (2013) Sugar,
uric acid, and the etiology of diabetes and obesity. Diabetes
62:3307–3315
10. Basu S, Yoffe P, Hills N, Lustig RH (2013) The relationship of
sugar to population level diabetes prevalence: an econometric
analysis of repeated cross-sectional data. PLoS ONE 8:e57873
11. Sánchez-Lozada LG, Mu W, Roncal C, Sautin YY, Abdelmalek
M, Reungjui S, Le M, Nakagawa T, Lan HY, Yu X, Johnson RJ
(2010) Comparison of free fructose and glucose to sucrose in the
ability to cause fatty liver. Eur J Nutr 49:1–9
12. Sakamoto E, Seino Y, Fukami A, Mizutani N, Tsunekawa S,
Ishikawa K, Ogata H, Uenishi E, Kamiya H, Hamada Y, Sato H,
Harada N, Toyoda Y, Miwa I, Nakamura J, Inagaki N, Oiso Y,
Ozaki N (2012) Ingestion of a moderate high-sucrose diet results
in glucose intolerance with reduced liver glucokinase activ-
ity and impaired glucagon-like peptide-1 secretion. J Diabetes
Investig 3:432–440
13. Klurfeld DM, Foreyt J, Angelopoulos TJ, Rippe JM (2013) Lack
of evidence for high fructose corn syrup as the cause of the obe-
sity epidemic. Int J Obes 37:771–773
14. Tappy L, Mittendorfer B (2012) Fructose toxicity: is the science
ready for public health actions? Curr Opin Clin Nutr Metab Care
15:357–361
15. Bravo S, Lowndes J, Sinnett S, Yu Z, Rippe J (2013) Consump-
tion of sucrose and high-fructose corn syrup does not increase
liver fat or ectopic fat deposition in muscles. Appl Physiol Nutr
Metab 38:681–688
16. Heden TD, Liu Y, Park YM, Nyhoff LM, Winn NC, Kanaley JA
(2014) Moderate amounts of fructose- or glucose-sweetened
beverages do not differentially alter metabolic health in male and
female adolescents. Am J Clin Nutr 100:796–805
17. Aeberli I, Hochuli M, Gerber PA, Sze L, Murer SB, Tappy L,
Spinas GA, Berneis K (2013) Moderate amounts of fructose
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
S23
Eur J Nutr (2016) 55 (Suppl 2):S17–S23
1 3
consumption impair insulin sensitivity in healthy young men.
Diabetes Care 36:150–156
18. Hokayem M, Blond E, Vidal H, Lambert K, Meugnier E, Feillet-
Coudray C, Coudray C, Pesenti S, Luyton C, Lambert-Porcheron
S, Sauvinet V, Fedou C, Brun JF, Rieusset J, Bisbal C, Sultan
A, Mercier J, Goudable J, Dupuy AM, Cristol JP, Laville M,
Avignon A (2013) Grape polyphenols prevent fructose-induced
oxidative stress and insulin resistance in first-degree relatives of
type 2 diabetic patients. Diabetes Care 36:1454–1461
19. Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer
AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W,
McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai
M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein
MK, Berglund L, Havel PJ (2009) Consuming fructose-sweet-
ened, not glucose-sweetened, beverages increases visceral adi-
posity and lipids and decreases insulin sensitivity in overweight/
obese humans. J Clin Invest 119:1322–1334
20. Lecoultre V, Egli L, Carrel G, Theytaz F, Kreis R, Schneiter P,
Boss A, Zwygart K, Lê KA, Bortolotti M, Boesch C, Tappy L
(2013) Effects of fructose and glucose overfeeding on hepatic
insulin sensitivity and intrahepatic lipids in healthy humans.
Obesity 21:782–785
21. Stanhope KL, Medici V, Bremer AA, Lee V, Lam HD, Nunez
MV, Chen GX, Keim NL, Havel PJ (2015) A dose-response
study of consuming high-fructose corn syrup-sweetened bever-
ages on lipid/lipoprotein risk factors for cardiovascular disease in
young adults. Am J Clin Nutr 101:1144–1154
22. Johnston RD, Stephenson MC, Crossland H, Cordon SM, Pal-
cidi E, Cox EF, Taylor MA, Aithal GP, Macdonald IA (2013) No
difference between high fructose and high glucose diets on liver
triacylglycerol or biochemistry in healthy overweight men. Gas-
troenterology 145:1016–1025
23. Te Morenga L, Mallard S, Mann J (2013) Dietary sugars and
body weight: systematic review and meta-analyses of ran-
domised controlled trials and cohort studies. BMJ 346:e7492
24. van Buul VJ, Tappy L, Brouns FJ (2014) Misconceptions about
fructose-containing sugars and their role in the obesity epidemic.
Nutr Res Rev 27:119–130
25. Bawden S, Stephenson M, Falcone Y, Lingaya M, Ciampi E,
Hunter K, Bligh F, Schirra J, Taylor M, Morris P, Macdonald
I, Gowland P, Marciani L, Aithal G (2016) Increased liver fat
and glycogen stores following high compared with low glycae-
mic index food: a randomized cross over study. Diabetes Obes
Metab. doi:10.1111/dom.12784
26. Atkinson FS, Foster-Powell K, Brand-Miller JC (2008) Interna-
tional tables of glycemic index and glycemic load values: 2008.
Diabetes Care 31:2281–2283
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... Our concerns regarding the adverse health effects of high sugar consumption likely originated from animal studies. Mice or rats have been used to identify the culprits of potential detrimental health effects associated with high sugar intake (41,42), as their genomes and organ systems are similar to those of humans, and they develop diseases in a comparable way to humans (43). However, mice and rats do differ from humans in the intermediary metabolism (44), which may undermine the translatability of rodent findings to advance human health (45). ...
... Instead, it almost always coexists together with glucose in the form of sucrose or HFCS. Since the metabolism of pure fructose and its associated health consequences is different from when fructose is consumed as part of sucrose or consumed with glucose (as in HFCS) (41), it is a far reach to translate the conclusions related to excessive pure fructose consumption in rodents into the human situation. Also, most animal studies failed to include a control group where only glucose was consumed; therefore, it is unknown whether the adverse health effects observed are due to the high monosaccharide (fructose) consumption per se or to the energy supplied by fructose specifically (41,42,53). ...
... Since the metabolism of pure fructose and its associated health consequences is different from when fructose is consumed as part of sucrose or consumed with glucose (as in HFCS) (41), it is a far reach to translate the conclusions related to excessive pure fructose consumption in rodents into the human situation. Also, most animal studies failed to include a control group where only glucose was consumed; therefore, it is unknown whether the adverse health effects observed are due to the high monosaccharide (fructose) consumption per se or to the energy supplied by fructose specifically (41,42,53). ...
Article
Sugar is widely consumed over the world. Although the mainstream view is that high added/free sugar consumption leads to obesity and related metabolic diseases, controversies exist. This narrative review aims to highlight important findings and identify major limitations and gaps in the current body of evidence in relation to the effect of high sugar intake on health. Previous animal studies have shown that high sucrose/fructose consumption causes insulin resistance in the liver, skeletal muscle and consequent hyperglycemia, mainly because of fructose-induced de novo hepatic lipogenesis. Evidence from human observational studies and clinical trials was however inconsistent, where most if not all studies linking high sugar intake to obesity focused on sugar-sweetened beverages (SSBs), and studies focusing on sugars from solid foods yielded null findings. In our opinion the substantial limitations in the current body of evidence such as short study duration, use of supraphysiological doses of sugar or fructose alone in animal studies, lack of direct comparison of the effects of solid vs. liquid sugars on health outcomes, as well as the lack of appropriate control seriously curtails the translatability of the findings to the real-world situation. It is quite possible that “high” sugar consumption at normal dietary doses (e.g., 25% daily energy intake) per se, i.e., the unique effect of sugar, especially in the solid form, may indeed not pose a health risk for individuals apart from the potential to reduce the overall dietary nutrient density, although newer evidence suggests “low” sugar intake (<5% daily energy intake) is just as likely to be associated with nutrient dilution. We argue the current public health recommendations to encourage the reduction of both solid and liquid forms of free sugars intake (e.g., sugar reformulation programs) should be revised due to the over-extrapolation of results from SSBs studies.
... Evidence of the role of free sugars is less consistent (8); although high intakes have been associated with increased risk of type 2 diabetes, it is unclear whether the detrimental effects are caused by free sugars per se or by their contribution to excess energy intake. Increased free sugars intake is associated with reduced insulin sensitivity (9,10), but it has been reported that a high intake of free sugars without excess energy may not have any detrimental impact on health (11). There is also some evidence for positive associations between single foods and an increased risk of developing type 2 diabetes, such as higher intakes of unprocessed and processed meat (12,13), fruit juices, sugar-sweetened beverages (SSBs), refined grains, sweets, and desserts (8,14) and low intakes of fresh fruit and vegetables (15). ...
... Total energy and nutrient intake data were automatically estimated by multiplying the number of portions consumed by the set quantity of each food portion size and its nutrient composition according to the UK Nutrient Databank food composition tables (2012-2013 and 2013-2014) (29). Energy density, saturated fatty acid (SFA), free sugars, and fiber density were selected because of their significant roles in the development of obesity and type 2 diabetes and their high frequency of intake in daily life (4,9,30). Energy density (kJ/g) was calculated by dividing total food energy (in kilojoules) by total food weight (grams); all beverages were excluded because of their disproportionate influence on total energy density value (31). ...
Article
Full-text available
OBJECTIVE To identify dietary patterns (DPs) characterized by a set of nutrients of concern and their association with incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS A total of 120,343 participants from the U.K. Biobank study with at least two 24 h dietary assessments were studied. Reduced rank regression was used to derive DPs explaining variability in energy density, free sugars, saturated fat, and fiber intakes. We investigated prospective associations with T2D using Cox proportional hazard models. RESULTS Over 8.4 years of follow-up from the latest dietary assessment, 2,878 participants developed T2D. Two DPs were identified that jointly explained a total of 63% variation in four nutrients. DP1 was characterized by high intakes of chocolate and confectionery, butter, low-fiber bread, and sugars and preserves, and low intakes of fruits and vegetables. DP1 was linearly associated with T2D in multivariable models without BMI adjustment (per z score, hazard ratio [HR] 1.11 [95% CI 1.08–1.14]) and after BMI adjustment (HR 1.09 [95% CI 1.06–1.12]). DP2 was characterized by high intakes of sugar-sweetened beverages, fruit juice, table sugars and preserves, and low intakes of high-fat cheese and butter, but showed no clear association with T2D. There were significant interactions between both DPs and age, with increased risks among younger people in DP1 (HR 1.13 [95% CI 1.09–1.18]) and DP2 (HR 1.10 [95% CI 1.05–1.15]), as well as with DP1 and BMI, with increased risks among people with obesity (HR 1.11 [95% CI 1.07–1.16]). CONCLUSIONS A DP characterized by high intakes of chocolate, confectionery, butter, low-fiber bread, and added sugars, and low in fresh fruits and vegetables intake is associated with a higher incidence of T2D, particularly among younger people and those with obesity.
... Participants were included in the study between 2006 and 2013. So far, four follow-up assessment rounds took place, i.e., T1=baseline, median (interquartile) months to follow-up rounds: T2=13 (13-15), T3=25 (23)(24)(25)(26)(27)(28), and T4=44 (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). Comprehensive physical examinations, biobanking, and questionnaires were conducted at T1 and T4, and follow-up questionnaires (including questions for diabetes status) were issued to participants at T2 and T3. ...
... In addition, the fact that the inverse association with baseline type 2 diabetes risk observed for the sweet snack pattern may be related to the layman's term for type 2 diabetes, which is "sugar disease" in Dutch and several other languages. Although there is still some scientific uncertainty as to whether all types of sugar intake are associated with risk of type 2 diabetes [45][46][47][48], limiting the consumption of energy dense, sugar-rich foods will be likely to benefit health, not only by reducing the risk of diabetes, but obesity and cardiovascular diseases as well [48]. Furthermore, it is worth noticing that the adherence to both two savory UPF patterns was higher among individuals with higher diabetes risk scores at baseline, and both patterns were also associated with a higher risk of incident type 2 diabetes. ...
Article
Full-text available
Background The overall consumption of ultra-processed food (UPF) has previously been associated with type 2 diabetes. However, due to the substantial heterogeneity of this food category, in terms of their nutritional composition and product type, it remains unclear whether previous results apply to all underlying consumption patterns of UPF. Methods Of 70,421 participants (35–70 years, 58.6% women) from the Lifelines cohort study, dietary intake was assessed with a food frequency questionnaire. UPF was identified according to the NOVA classification. Principal component analysis (PCA) was performed to derive UPF consumption patterns. The associations of UPF and adherence to UPF consumption patterns with incidence of type 2 diabetes were studied with logistic regression analyses adjusted for age, sex, diet quality, energy intake, alcohol intake, physical activity, TV watching time, smoking status, and educational level. Results During a median follow-up of 41 months, a 10% increment in UPF consumption was associated with a 25% higher risk of developing type 2 diabetes (1128 cases; OR 1.25 [95% CI 1.16, 1.34]). PCA revealed four habitual UPF consumption patterns. A pattern high in cold savory snacks (OR 1.16 [95% CI 1.09, 1.22]) and a pattern high in warm savory snacks (OR 1.15 [95% CI 1.08, 1.21]) were associated with an increased risk of incident type 2 diabetes; a pattern high in traditional Dutch cuisine was not associated with type 2 diabetes incidence (OR 1.05 [95% CI 0.97, 1.14]), while a pattern high in sweet snacks and pastries was inversely associated with type 2 diabetes incidence (OR 0.82 [95% CI 0.76, 0.89]). Conclusions The heterogeneity of UPF as a general food category is reflected by the discrepancy in associations between four distinct UPF consumption patterns and incident type 2 diabetes. For better public health prevention, research is encouraged to further clarify how different UPF consumption patterns are related to type 2 diabetes.
... HSDs, sucrose, and thus glucose and fructose cause dysregulation of lipid and carbohydrate metabolism in the body. Added sugar bingeing promotes an increased energy balance, weight gain, fat storage and consequently overweight and/or obesity [32][33][34][35]. An increase in high-sugar products and added sugar consumption has been observed since the 1980s (more visible in the USA) and suggests that sugar, not including fat, is the major factor contributing to and driving the current obesity epidemic and diabetes [36,37]. ...
Article
Full-text available
Carbohydrates are important macronutrients in human and rodent diet patterns that play a key role in crucial metabolic pathways and provide the necessary energy for proper body functioning. Sugar homeostasis and intake require complex hormonal and nervous control to proper body energy balance. Added sugar in processed food results in metabolic, cardiovascular, and nervous disorders. Epidemiological reports have shown enhanced consumption of sweet products in children and adults, especially in reproductive age and in pregnant women, which can lead to the susceptibility of offspring’s health to diseases in early life or in adulthood and proneness to mental disorders. In this review, we discuss the impacts of high-sugar diet (HSD) or sugar intake during the perinatal and/or postnatal periods on neural and behavioural disturbances as well as on the development of substance use disorder (SUD). Since several emotional behavioural disturbances are recognized as predictors of SUD, we also present how HSD enhances impulsive behaviour, stress, anxiety and depression. Apart from the influence of HSD on these mood disturbances, added sugar can render food addiction. Both food and addictive substances change the sensitivity of the brain rewarding neurotransmission signalling. The results of the collected studies could be important in assessing sugar intake, especially via maternal dietary patterns, from the clinical perspective of SUD prevention or pre-existing emotional disorders. Methodology: This narrative review focuses on the roles of a high-sugar diet (HSD) and added sugar in foods and on the impacts of glucose and fructose on the development of substance use disorder (SUD) and on the behavioural predictors of drugs abuse. The literature was reviewed by two authors independently according to the topic of the review. We searched the PubMed and Scopus databases and Multidisciplinary Digital Publishing Institute open access scientific journals using the following keyword search strategy depending on the theme of the chapter: “high-sugar diet” OR “high-carbohydrate diet” OR “sugar” OR “glucose” OR “fructose” OR “added sugar” AND keywords. We excluded inaccessible or pay-walled articles, abstracts, conference papers, editorials, letters, commentary, and short notes. Reviews, experimental studies, and epidemiological data, published since 1990s, were searched and collected depending on the chapter structure. After the search, all duplicates are thrown out and full texts were read, and findings were rescreened. After the selection process, appropriate papers were included to present in this review.
... In addition, it is one of the major tissues responsible for glucose homeostasis, as approximately 80% of the glucose utilization occurs in the skeletal muscle [3]. Moreover, an increasing number of studies have demonstrated that T2DM causes dramatic structural, metabolic, and functional changes in skeletal muscle fibers, such as muscle atrophy [4], fiber-type transition [5], decreased myogenic differentiation ability, impaired glucose uptake [6], and fatty acid oxidation [7]. Skeletal muscle dysfunction, together with other diabetic complications, seriously affects the quality of life and physical activity of patients and increases the risk of death [8,9]. ...
Article
Full-text available
Background Type 2 diabetes mellitus is a global health problem. It often leads to a decline in the differentiation capacity of myoblasts and progressive loss of muscle mass, which in turn results in deterioration of skeletal muscle function. However, effective therapies against skeletal muscle diseases are unavailable. Methods Skeletal muscle mass and differentiation ability were determined in db/+ and db/db mice. Transcriptomics and metabolomics approaches were used to explore the genetic mechanism regulating myoblast differentiation in C2C12 myoblasts. Results In this study, the relatively uncharacterized solute carrier family gene Slc2a6 was found significantly up-regulated during myogenic differentiation and down-regulated during diabetes-induced muscle atrophy. Moreover, RNAi of Slc2a6 impaired the differentiation and myotube formation of C2C12 myoblasts. Both metabolomics and RNA-seq analyses showed that the significantly differentially expressed genes (e.g., LDHB) and metabolites (e.g., Lactate) during the myogenic differentiation of C2C12 myoblasts post- Slc2a6 -RNAi were enriched in the glycolysis pathway. Furthermore, we show that Slc2a6 regulates the myogenic differentiation of C2C12 myoblasts partly through the glycolysis pathway by targeting LDHB, which affects lactic acid accumulation. Conclusion Our study broadens the understanding of myogenic differentiation and offers the Slc2a6 -LDHB axis as a potential therapeutic target for the treatment of diabetes-associated muscle atrophy.
... Four nutrient response variables were included: energy density (kJ/g), saturated fat (% total energy), free sugars (% total energy) and fiber density (g/MJ). These nutrient variables have established associations with the development of obesity, type 2 diabetes and CVD (57)(58)(59)(60)(61)(62)(63)(64)(65)(66) , which underscores the importance of a well-supported hypothesis underlying the proposed research. From the initial baseline cohort, a subsample of participants that provided at least two 24-h questionnaires (n~117,000 (11) ; n~120,000 (12) ) and free of disease at baseline, were included and the mean dietary intake across multiple assessments was calculated to derive dietary patterns. ...
Article
Full-text available
Most current nutrition policies and dietary recommendations still reflect decades of research addressing the mechanism of action or health risks of individual nutrients. Yet, most high-income countries including the UK are far from reaching the dietary intakes which are recommended for good health. Food-based dietary patterns (DPs) can help target specific combinations of foods that are associated with disease risk, recognising the coexistence of multiple nutrients within foods and their potential synergistic effects. Reduced rank regression (RRR) has emerged as a useful exploratory approach which uses a priori knowledge of the pathway from diet to disease to help identify DPs which are associated with disease risk in a particular population. Here we reviewed the literature with a focus on longitudinal cohort studies using RRR to derive DPs and reporting associations with non-communicable disease risk. We also illustrated the application of the RRR approach using data from the UK Biobank study, where we derived DPs that explained high variability in a set of nutrient response variables. The main DP was characterised by high intakes of chocolate and confectionery, butter and low-fibre bread, and low intakes of fresh fruit and vegetables and showed particularly strong associations with CVD, type 2 diabetes and all-cause mortality, which is consistent with previous studies that derived 'Western' or unhealthy DPs. These recent studies conducted in the UK Biobank population together with evidence from previous cohort studies contribute to the emerging evidence base to underpin food-based dietary advice for non-communicable disease prevention.
... One of the NCD risk factors is obesity, which induced by high consumption of sugar. High sugar diet increases the risk of obesity and type II diabetes (MacDonald, 2016, Savona, 2018. A longitudinal study showed that high sugar-sweetened beverage (SSB) consumption is linked to high waist-to-hip ratio (Hodge et al., 2018). ...
... Diyet karbonhidratlarının veya toplam enerji alımının insülin düzeyi üzerindeki etkisi önemlidir. 40 Düşük karbonhidrat/yüksek yağ alımının azalmış glukoz toleransı ve insülin direnci ile ilişkili olduğu en az 80 yıldır bilinmektedir. 41 Çeşitli etmenler lipolizi veya lipogenezi etkileyerek yağ dokusu miktarında azalmaya veya artışa neden olmaktadır. ...
Chapter
Full-text available
Today demand for body contouring is increasing. Reduction of the targeted amount of adipose tissue non-invasive interventions takes over because of the long recovery time in surgical interventions. Noninvasive methods such as cryolipolysis, radiofrequency, low-level laser therapy and high-intensity focused ultrasound are available to reduce subcutaneous fat, celluloid volume. Nutritional habits are effective in body weight and celluloid formation. Individuals' dietary habits may increase the effectiveness of the applied method and ensure that current shape of body is sustainable during and after non-invasive interventions. Nutrition program should be established under the medical history. Individuals' daily energy requirement should be met at recommended level. Foods with low glycemic index, high fiber content, little or no sugar, and low total fat content should be preferred. The aim of this review is to present the basic principles of an adequate and balanced nutrition program increase the effectiveness of body shaping and celluloid treatment considering evidence-based information.
... The appeal (hedonic response) of sweetness is a key driver of consuming foods high in added sugars [1,2]. Overconsumption of added sugars contributes to increased risk of obesity and related chronic illnesses such as type 2 diabetes mellitus and cardiovascular disease [3][4][5]. A number of leading health agencies have recommended a reduction in intake of added sugars to improve public health and prevent chronic disease [6,7]. ...
Article
Full-text available
Sweetness drives the consumption of added sugars, so understanding how to best measure sweet hedonics is important for developing strategies to lower sugar intake. However, methods to assess hedonic response to sweetness vary, making results across studies difficult to integrate. We compared methods to measure optimal sucrose concentration in 21 healthy adults (1) using paired-comparison preference tracking vs. ratings of liking, (2) with participants in the laboratory vs. at home, and (3) using aqueous solutions vs. vanilla milk. Tests were replicated on separate days to assess test-retest reliability. Test-retest reliability was similar between laboratory and home testing, but tended to be better for vanilla milk and preference tracking. Optimal sucrose concentration was virtually identical between laboratory and home, slightly lower when estimated via preference tracking, and about 50% lower in vanilla milk. However, optimal sucrose concentration correlated strongly between methods, locations, and stimuli. More than 50% of the variability in optimal sucrose concentration could be attributed to consistent differences among individuals, while much less variability was attributable to differences between methods. These results demonstrate convergent validity between methods, support testing at home, and suggest that aqueous solutions can be useful proxies for some commonly consumed beverages for measuring individual differences.
... Compared with glucose, fructose may be a poor substrate for de novo lipogenesis in enterocytes 55 , and fatty acid accumulation might impair intestinal function. Thus, excessive sucrose intake has been recognized as a primary cause of metabolic syndrome, the toxicity resulting from excess fructose rather than sucrose, as fructose undergoes glycation to proteins and, physiologically, its metabolic substrate rapidly flows into de novo lipogenesis, which promotes liver inflammation 72 . Additionally, the pro-oxidative and proinflammatory effects of J o u r n a l P r e -p r o o f fructose lead to an increase in gut permeability and endotoxemia that exacerbate chronic inflammation 18,73 . ...
Article
Sugar overconsumption is linked to a rise in the incidence of noncommunicable diseases such as diabetes, cardiovascular diseases and cancer. This increased incidence is becoming a real public health problem that is more severe than infectious diseases, contributing to 35 million deaths annually. Excessive intake of free sugars can cause many of the same health problems as excessive alcohol consumption. Many recent international recommendations have expressed concerns about sugar consumption in Westernized societies, as current consumption levels represent quantities with no precedent during hominin evolution. In both adults and children, the World Health Organization strongly recommends reducing free sugar intake to less than 10% of total energy intake and suggests a further reduction to below 5%. Most studies have focused on the deleterious effects of Western dietary patterns on global health and the intestine. Whereas excessive dietary fat consumption is well studied, the specific impact of sugar is poorly described, while refined sugars represent up to 40% of caloric intake within industrialized countries. However, high sugar intake is associated with multiple tissue and organ dysfunctions. Both hyperglycemia and excessive sugar intake disrupt the intestinal barrier, thus increasing gut permeability and causing profound gut microbiota dysbiosis, which results in a disturbance in mucosal immunity that enhances infection susceptibility. This review aims to highlight the roles of different types of dietary carbohydrates and the consequences of their excessive intake for intestinal homeostasis.
Article
Full-text available
As nutrition-related chronic diseases have become more and more frequent, the importance of dietary prevention has also increased. Dietary fat plays a major role in human nutrition, and modification of fat and/or fatty acid intake could have a preventive potential. The aim of the guideline of the German Nutrition Society (DGE) was to systematically evaluate the evidence for the prevention of the widespread diseases obesity, type 2 diabetes mellitus, dyslipoproteinaemia, hypertension, metabolic syndrome, coronary heart disease (CHD), stroke, and cancer through the intake of fat or fatty acids. The main results can be summarized as follows: it was concluded with convincing evidence that a reduced intake of total and saturated fat as well as a larger intake of polyunsaturated fatty acids (PUFA) at the expense of saturated fatty acids (SFA) reduces the concentration of total and low-density lipoprotein cholesterol in plasma. Furthermore, there is convincing evidence that a high intake of trans fatty acids increases risk of dyslipoproteinaemia and that a high intake of long-chain polyunsaturated n-3 fatty acids reduces the triglyceride concentration in plasma. A high fat intake increases the risk of obesity with probable evidence when total energy intake is not controlled for (ad libitum diet). When energy intake is controlled for, there is probable evidence for no association between fat intake and risk of obesity. A larger intake of PUFA at the expense of SFA reduces risk of CHD with probable evidence. Furthermore, there is probable evidence that a high intake of long-chain polyunsaturated n-3 fatty acids reduces risk of hypertension and CHD. With probable evidence, a high trans fatty acid intake increases risk of CHD. The practical consequences for current dietary recommendations are described at the end of this article.
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The intake of added sugars, such as from table sugar (sucrose) and high-fructose corn syrup has increased dramatically in the last hundred years and correlates closely with the rise in obesity, metabolic syndrome, and diabetes. Fructose is a major component of added sugars and is distinct from other sugars in its ability to cause intracellular ATP depletion, nucleotide turnover, and the generation of uric acid. In this article, we revisit the hypothesis that it is this unique aspect of fructose metabolism that accounts for why fructose intake increases the risk for metabolic syndrome. Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake. These studies challenge the long-standing dogma that "a calorie is just a calorie" and suggest that the metabolic effects of food may matter as much as its energy content. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provides new insights into pathogenesis and therapies for this important disease.
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Background: Adolescents consume more sugar-sweetened beverages than do individuals in any other age group, but it is unknown how the type of sugar-sweetened beverage affects metabolic health in this population. Objective: The objective was to compare the metabolic health effects of short-term (2-wk) consumption of high-fructose (HF) and high-glucose (HG)-sweetened beverages in adolescents (15-20 y of age). Design: In a counterbalanced, single-blind fashion, 40 male and female adolescents completed two 2-wk trials that included 1) an HF trial in which they consumed 710 mL of a sugar-sweetened beverage/d (equivalent to 50 g fructose/d and 15 g glucose/d) for 2 wk and 2) an HG trial in which they consumed 710 mL of a sugar-sweetened beverage/d (equivalent to 50 g glucose/d and 15 g fructose/d) for 2 wk in addition to their normal ad libitum diet. In addition, the participants maintained similar physical activity levels during each trial. The day after each trial, insulin sensitivity and resistance [assessed via Quantitative Insulin Sensitivity Check Index (QUICKI) and homeostatic model assessment of insulin resistance (HOMA-IR) index] and fasting and postprandial glucose, lactate, lipid, cholesterol, insulin, C-peptide, insulin secretion, and clearance responses to HF or HG mixed meals were assessed. Results: Body weight, QUICKI (whole-body insulin sensitivity), HOMA-IR (hepatic insulin resistance), and fasting lipids, cholesterol, glucose, lactate, and insulin secretion or clearance were not different between trials. Fasting HDL- and HDL₃-cholesterol concentrations were ∼10-31% greater (P < 0.05) in female adolescents than in male adolescents. Postprandial triacylglycerol, HDL-cholesterol, HDL₃-cholesterol, and glucose concentrations were not different between HF and HG trials. The lactate incremental area under the curve was ∼3.7-fold greater during the HF trial (P < 0.05), whereas insulin secretion was 19% greater during the HG trial (P < 0.05). Conclusions: Moderate amounts of HF- or HG-sweetened beverages for 2 wk did not have differential effects on fasting or postprandial cholesterol, triacylglycerol, glucose, or hepatic insulin clearance in weight-stable, physically active adolescents.
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Aims/Introduction: Excessive intake of sucrose can cause severe health issues, such as diabetes mellitus. In animal studies, consumption of a high‐sucrose diet (SUC) has been shown to cause obesity, insulin resistance and glucose intolerance. However, several in vivo experiments have been carried out using diets with much higher sucrose contents (50–70% of the total calories) than are typically ingested by humans. In the present study, we examined the effects of a moderate SUC on glucose metabolism and the underlying mechanism. Materials and Methods: C57BL/6J mice received a SUC (38.5% sucrose), a high‐starch diet (ST) or a control diet for 5 weeks. We assessed glucose tolerance, incretin secretion and liver glucose metabolism. Results: An oral glucose tolerance test (OGTT) showed that plasma glucose levels in the early phase were significantly higher in SUC‐fed mice than in ST‐fed or control mice, with no change in plasma insulin levels at any stage. SUC‐fed mice showed a significant improvement in insulin sensitivity. Glucagon‐like peptide‐1 (GLP‐1) secretion 15 min after oral glucose administration was significantly lower in SUC‐fed mice than in ST‐fed or control mice. Hepatic glucokinase (GCK) activity was significantly reduced in SUC‐fed mice. During the OGTT, the accumulation of glycogen in the liver was suppressed in SUC‐fed mice in a time‐dependent manner. Conclusions: These results indicate that mice that consume a moderate SUC show glucose intolerance with a reduction in hepatic GCK activity and impairment in GLP‐1 secretion. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00208.x, 2012)
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& Aims: Diets high in fructose have been proposed to contribute to non-alcoholic fatty liver disease (NAFLD). We compared the effects of high-fructose and matched glucose intake on hepatic triacylglycerol (TAG) concentration and other liver parameters. In a double-blind study, we randomly assigned 32 healthy but centrally overweight men to groups that received either a high-fructose or high-glucose diet (25% energy). These diets were provided during an initial isocaloric period of 2 weeks, followed by a 6-week washout period and then again during a hypercaloric 2 week period. The primary outcome measure was hepatic level of TAG, with additional assessments of TAG levels in serum and soleus muscle, hepatic levels of ATP, and systemic and hepatic insulin resistance. During the isocaloric period of the study, both groups had stable body weights and concentrations of TAG in liver, serum, and soleus muscle. The high-fructose diet produced an increase of 22±52 μmol/L in serum level of uric acid, whereas the high-glucose diet led to a reduction of 23±25 μmol/L (P<.01). The high-fructose diet also produced an increase of 0.8±0.9 in the homeostasis model assessment of insulin resistance, whereas the high-glucose diet produced an increase of only 0.1±0.7 (P=.03). During the hypercaloric period, participants in the high-fructose and high-glucose groups had similar increases in weight (1.0±1.4 kg vs 0.6±1.0 kg; P=.29) and absolute concentration of TAG in liver (1.70±2.6% vs 2.05±2.9%; P=.73) and serum (0.36±0.75 mmol/L vs 0.33±0.38 mmol/L; P=.91), and similar results in biochemical assays of liver function. Body weight changes were associated with changes in liver biochemistry and concentration of TAGs. In the isocaloric period, overweight men on neither a high-fructose nor a high-glucose diet developed any significant changes in hepatic concentration of TAGs or serum levels of liver enzymes. However, in the hypercaloric period both high-fructose and high-glucose diets produced significant increases in these parameters without any significant difference between the 2 groups. This indicates an energy-mediated, rather than specific macronutrient-mediated effect. Clinical trials.gov no: NCT01050140.