The Role of Diet and Nutrition in Prevention and Management of Type

Tow Diabetes and Related Complications

Problem :
* The lack of a specific nutritional plan followed for patients of this type .
•The absence of individual awareness of these systems and the emergence of many
untrustworthy nutritional articles.
• Different methods of prevention differ according to people and their cases, which
means that individual treatment and diagnosis of cases
•The proposed diets are not comprehensive in terms of the potential risks that may
harm this patient because he has a disease other than Type II diabetes.

Objectives:
- General objectives :
 To determine the effect and role of Diet in prevention of Type 2 diabetes
and related complications.
- Specific objectives :
 To examine the current scientific knowledge on the relationship between
diet and Type 2 diabetes
 To evaluate the impact of dietary treatment on blood glucose
concentrations, blood lipid concentrations, maintain normal levels of arterial
pressure, and provide appropriate energy for healthy weight, normal growth,
and development.
 To abandon medications if possible. To improve health through balanced
nutrition.

Literature review :
1. Chronic conditions such as obesity, diabetes, and dementia are increasing in
the United States (US) population. Knowledge of these chronic conditions,
preventative measures, and proper management tactics is important and
critical to preventing disease. The overlap between obesity, diabetes, and
dementia is becoming further elucidated. These conditions share a similar
origin through the components of increasing age, gender, genetic and
epigenetic predispositions, depression, and a high-fat Western diet (WD) that
all contribute to the inflammatory state associated with the development of
obesity, diabetes, and dementia. This inflammatory state leads to the
dysregulation of food intake and insulin resistance. Obesity is often the
cornerstone that leads to the development of diabetes and, subsequently, in
the case of type 2 diabetes mellitus (T2DM), progression to "type 3 diabetes
 mellitus (T3DM)". Obesity and depression are closely associated with diabetes.
However, dementia can be avoided with lifestyle modifications, by switching
to a plant-based diet (e.g., a Mediterranean diet (MD)), and increasing
physical activity. Diet and exercise are not the only treatment options. There
are several surgical and pharmacological interventions available for
prevention. Current and future research within each of these fields is
warranted and offers the chance for new treatment options and a better
understanding of the pathogenesis of each condition.
2. The Western diet increased caloric intake for the first 6 months and body fat,
activity, energy expenditure, insulin resistance, and hepatosteatosis after 2.5
years, whereas the Mediterranean diet reduced triglyceride levels , This is the
first report of differential caloric intake and obesity with long-term
consumption of a Western versus Mediterranean diet under controlled
experimental conditions and the first experimental evidence that a
Mediterranean diet protects against hepatosteatosis compared with a
Western diet.
3. Dietary composition is associated with the differential prevalence of
psychiatric disorders; the Western diet confers increased risk, while the
Mediterranean diet appears to reduce risk. In nonhuman primates, anxiety-
like behaviors and social isolation have been linked to both Western diet
consumption and increased inflammatory disease risk, and recent evidence
suggests that diet composition may affect immune system function in part
through its effects on behavior. This is particularly important in the context of
the global COVID-19 pandemic in which social isolation has been associated
with disease. Here, we examined the effects of Western- and Mediterranean-
like diets on social behavior in a randomized, 34-month preclinical trial in
middle-aged female cynomolgus macaques (Macaca fascicularis). Diet
induced rapid and persistent changes in a suite of behaviors. After just three
months of experimental diet consumption, a composite measure of diet-
altered behavior (DAB) significantly differed between the two diets (p = 0.014)
and remained different throughout the 24-month experimental observation
period (p = 2.2 × 10-8). Monkeys fed the Western diet spent more time alone
(FDR = 4.4 × 10-5) and displayed more anxiety behavior (FDR = 0.048),
whereas monkeys fed the Mediterranean diet spent more time resting (FDR =
0.0013), attentive (FDR = 0.017), and in body contact with groupmates (FDR =
4.1 × 10-8). These differences were largely due to changes in behavior of
animals fed the Mediterranean diet, while Western-diet-fed-animals exhibited
similar behaviors compared to the eight-month baseline period, during which
all monkeys consumed a common laboratory diet. These observations provide
experimental support in a nonhuman primate model, demonstrating a
potential therapeutic benefit of the Mediterranean diet consumption to
reduce social isolation and anxiety and thus mitigate social isolation-
associated disorders that often accompany illness and disability.
4. We found that consumption of a Western diet resulted in significantly higher
mitochondrial respiration with fatty acid oxidation (FAO) (53%), FAO +
 complex I (52%), complex I + II (31%), max electron transport system (ETS)
(31%), and ETS rotenone sensitive (31%) than did consumption of a
Mediterranean diet. In addition, measures of respiration in response to fatty
acids were significantly and positively correlated with both insulin resistance
and plasma insulin concentrations. , This study highlights the importance of
dietary composition in mitochondrial bioenergetics and that diet can
influence skeletal muscle mitochondrial respiration independently of other
factors such as macronutrient composition.
5. Mitochondrial dysfunction is evident in diseases affecting cognition and
metabolism such as Alzheimer's disease and type 2 diabetes. Human studies
of brain mitochondrial function are limited to postmortem tissue, preventing
the assessment of bioenergetics by respirometry. Here, we investigated the
effect of two diets on mitochondrial bioenergetics in three brain regions: the
prefrontal cortex (PFC), the entorhinal cortex (ERC), and the cerebellum (CB),
using middle-aged nonhuman primates. Eighteen female cynomolgus
macaques aged 12.3 ± 0.7 yr were fed either a Mediterranean diet that is
associated with healthy outcomes or a Western diet that is associated with
poor cognitive and metabolic outcomes. Average bioenergetic capacity within
each brain region did not differ between diets. Distinct brain regions have
different metabolic requirements related to their function and disease
susceptibility. Therefore, we also examined differences in bioenergetic
capacity between brain regions. Mitochondria isolated from animals fed a
Mediterranean diet maintained distinct differences in mitochondrial
bioenergetics between brain regions, whereas animals fed the Western diet
had diminished distinction in bioenergetics between brain regions. Notably,
fatty acid β-oxidation was not affected between regions in animals fed a
Western diet. In addition, bioenergetics in animals fed a Western diet had
positive associations with fasting blood glucose and insulin levels in PFC and
ERC mitochondria but not in CB mitochondria. Altogether, these data indicate
that a Western diet disrupts bioenergetic patterns across brain regions and
that circulating blood glucose and insulin levels in Western-diet fed animals
influence bioenergetics in brain regions susceptible to Alzheimer's disease
and type 2 diabetes.NEW & NOTEWORTHY We show that compared with
cynomolgus macaques fed a Mediterranean diet, a Western diet resulted in
diminished bioenergetic pattern between brain regions related to blood
glucose and insulin levels, specifically in brain regions susceptible to
neurodegeneration and diabetes. In addition, fatty acid metabolism not
directly linked to the TCA cycle and glucose metabolism did not show
differences in bioenergetics due to diet.
6. The lack of effective disease-modifying therapeutics to tackle Alzheimer's
disease (AD) is unsettling considering the actual prevalence of this
devastating neurodegenerative disorder worldwide. Intermittent hypoxic
conditioning (IHC) is a powerful non-pharmacological procedure known to
enhance brain resilience. In this context, the aim of the present study was to
investigate the potential long-term protective impact of IHC against AD-
 related phenotype, putting a special focus on cognition and mitochondrial
bioenergetics and dynamics. For this purpose, six-month-old male triple
transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two
weeks and the behavioral assessment was performed at 8.5 months of age,
while the sacrifice of mice occurred at nine months of age and their brains
were removed for the remaining analyses. Interestingly, IHC was able to
prevent anxiety-like behavior and memory and learning deficits and
significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice.
Concerning brain energy metabolism, IHC caused a significant increase in
brain cortical levels of glucose and a robust improvement of the
mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the
significant increase in mitochondrial membrane potential (ΔΨm) and
respiratory control ratio (RCR). Notably, the improvement of mitochondrial
bioenergetics seems to result from an adaptative coordination of the distinct
but intertwined aspects of the mitochondrial quality control axis. Particularly,
our results indicate that IHC favors mitochondrial fusion and promotes
mitochondrial biogenesis and transport and mitophagy in the brain cortex of
3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-
associated protein 25 kDa (SNAP-25) levels and a significant increase in both
glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a
remodeling of the synaptic microenvironment. Overall, these results
demonstrate the effectiveness of the IHC paradigm in forestalling the AD-
related phenotype in the 3×Tg-AD mouse model, offering new insights to AD
therapy and forcing a rethink concerning the potential value of non-
pharmacological interventions in clinical practice
7. Excessive mitochondrial fission is a prominent early event and contributes to
mitochondrial dysfunction, synaptic failure, and neuronal cell death in the
progression of Alzheimer's disease (AD). However, it remains to be
determined whether inhibition of excessive mitochondrial fission is beneficial
in mammal models of AD. To determine whether dynamin-related protein 1
(Drp1), a key regulator of mitochondrial fragmentation, can be a disease-
modifying therapeutic target for AD, we examined the effects of Drp1
inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric
amyloid-β (Aβ) in neurons and neuropathology and cognitive functions in Aβ
precursor protein/presenilin 1 double-transgenic AD mice. Inhibition of Drp1
alleviates mitochondrial fragmentation, loss of mitochondrial membrane
potential, reactive oxygen species production, ATP reduction, and synaptic
depression in Aβ-treated neurons. Furthermore, Drp1 inhibition significantly
improves learning and memory and prevents mitochondrial fragmentation,
lipid peroxidation, BACE1 expression, and Aβ deposition in the brain in the AD
model. These results provide evidence that Drp1 plays an important role in
Aβ-mediated and AD-related neuropathology and in cognitive decline in an
AD animal model. Therefore, inhibiting excessive Drp1-mediated
mitochondrial fission may be an efficient therapeutic avenue for
AD.SIGNIFICANCE STATEMENT Mitochondrial fission relies on the
 evolutionary conserved dynamin-related protein 1 (Drp1). Drp1 activity and
mitochondria fragmentation are significantly elevated in the brains of
sporadic Alzheimer's disease (AD) cases. In the present study, we first
demonstrated that the inhibition of Drp1 restored amyloid-β (Aβ)-mediated
mitochondrial dysfunctions and synaptic depression in neurons and
significantly reduced lipid peroxidation, BACE1 expression, and Aβ deposition
in the brain of AD mice. As a result, memory deficits in AD mice were rescued
by Drp1 inhibition. These results suggest that neuropathology and combined
cognitive decline can be attributed to hyperactivation of Drp1 in the
pathogenesis of AD. Therefore, inhibitors of excessive mitochondrial fission,
such as Drp1 inhibitors, may be a new strategy for AD.
8. The purpose of our study was to understand the protective effects of reduced
expression of dynamin-related protein (Drp1) against amyloid beta (Aβ)
induced mitochondrial and synaptic toxicities in Alzheimer's disease (AD)
progression and pathogenesis. Our recent molecular and biochemical studies
revealed that impaired mitochondrial dynamics-increased mitochondrial
fragmentation and decreased fusion-in neurons from autopsy brains of AD
patients and from transgenic AD mice and neurons expressing Aβ, suggesting
that Aβ causes mitochondrial fragmentation in AD. Further, our recent co-
immunoprecipitation and immunostaining analysis revealed that the
mitochondrial fission protein Drp1 interacted with Aβ, and this interaction
increased as AD progressed. Based on these findings, we hypothesize that a
partial deficiency of Drp1 inhibits Drp1-Aβ interactions and protects Aβ-
induced mitochondrial and synaptic toxicities, and maintains mitochondrial
dynamics and neuronal function in AD neurons. We crossed Drp1+/- mice
with APP transgenic mice (Tg2576 line) and created double mutant
(APPXDrp1+/-) mice. Using real-time RT-PCR and immunoblotting analyses,
we measured mRNA expressions and protein levels of genes related to the
mitochondrial dynamics, mitochondrial biogenesis and synapses from 6-
month-old Drp1+/-, APP, APPXDrp1+/- and wild-type (WT) mice. Using
biochemical methods, we also studied mitochondrial function and measured
soluble Aβ in brain tissues from all lines of mice in our study. Decreased
mRNA expressions and protein levels of Drp1 and Fis1 (fission) and CypD
(matrix) genes, and increased levels of Mfn1, Mfn2 and Opa1 (fusion), Nrf1,
Nrf2, PGC1α, TFAM (biogenesis) and synaptophysin, PSD95, synapsin 1,
synaptobrevin 1, neurogranin, GAP43 and synaptopodin (synaptic) were found
in 6-month-old APPXDrp1+/- mice relative to APP mice. Mitochondrial
functional assays revealed that mitochondrial dysfunction is reduced in
APPXDrp1+/- mice relative to APP mice, suggesting that reduced
Drp1enhances mitochondrial function in AD neurons. Sandwich ELISA assay
revealed that soluble Aβ levels were significantly reduced in APPXDrp1+/-
mice relative to APP mice, indicating that reduced Drp1 decreases soluble Aβ
production in AD progression. These findings suggest that a partial reduction
of Drp1 reduces Aβ production, reduces mitochondrial dysfunction, and
maintains mitochondrial dynamics, enhances mitochondrial biogenesis and
 synaptic activity in APP mice. These findings may have implications for the
development of Drp1 based therapeutics for AD patients
9.  Twenty-one participants were recruited and 19 completed the studies. The
low-carbohydrate diet induced lower insulin and glucose excursions
compared with the low-fat diet (p<0.0005 for both AUC). The insulin-response
following the single Mediterranean-style lunch-meal was more pronounced
than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet:
4.35 ± 2.2, of Mediterranean-style diet: 8.12 ± 5.2, p = 0.001) while
postprandial glucose levels were similar. The increase-ratio of insulin
correlated with the elevation of the incretin glucose-dependent
insulinotropic-polypeptide following the Mediterranean-style diet lunch
(Spearman, r = 0.64, p = 0.003).
10. Postbreakfast glucose and GIP AUCs were lower after the protein (17%) vs.
after the carbohydrate (23%) condition (P < 0.05), whereas postbreakfast
insulin, C-peptide, glucagon, and GLP-1 AUCs were not different between
conditions. A protein-rich breakfast may reduce the consequences of
hyperglycemia in this population. Postlunch insulin, C-peptide, and GIP AUCs
were greater after the protein condition vs. after the carbohydrate condition
(second-meal phenomenon; all, P < 0.05), but postlunch AUCs were not
different between conditions. The overall glucose, glucagon, and GLP-1
responses (e.g., 8 h) were greater after the protein condition vs. after the
carbohydrate condition (all, P < 0.05).
11. The third low-carbohydrate meal, but not the high-carbohydrate meal,
reduced: (1) evening insulin AUC by 39% without exercise and by 31% after
exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and
(3) evening insulin resistance by 37% without exercise and by 24% after
exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering
effects of low-carbohydrate diet, but exacerbated evening hyperglycemia
12. While adjustment of total energy and nutritional balance is critically
important, meal sequence, a relatively simple method of correcting
postprandial hyperglycemia, is becoming established as a practical dietary
approach for prevention and management of diabetes and obesity. Meal
sequence, i.e., consumption of protein and/or fat before carbohydrate,
promotes secretion of glucagon-like peptide-1 (GLP-1) from the gut and
ameliorates secretions of insulin and glucagon and delays gastric emptying,
thereby improving postprandial glucose excursion. GLP-1 is known to
suppress appetite by acting on the hypothalamus via the afferent vagus nerve.
Thus, enhancement of GLP-1 secretion by meal sequence is expected to
reduce body weight. Importantly, consumption of a diet rich in saturated fatty
acids such as meat dishes before carbohydrate increases secretions of not
only GLP-1 but also glucose-dependent insulinotropic polypeptide (GIP),
which promotes energy storage in adipose tissue and may lead to weight gain
in the long term. Dietary fiber intake before carbohydrate intake significantly
reduces postprandial glucose elevation and may have a weight loss effect, but
this dietary strategy does not enhance the secretion of GLP-1. Thus, it is
 suggested that their combination may have additive effects on postprandial
glucose excursion and body weight. Indeed, results of some clinical research
supports the idea that ingesting dietary fiber together with meal sequence of
protein and/or fat before carbohydrate benefits metabolic conditions of
individuals with diabetes and obesity.
13. The present study investigated the effect of apple consumption on
postprandial blood glucose and insulin levels in subjects with normal versus
impaired glucose tolerance. The study participants were ten healthy subjects
with no glucose intolerance (normal subjects) (mean, 24.4 ± 4.8 years) and
nine subjects with impaired glucose tolerance (mean, 45.2 ± 11.1 years,
including 2 on insulin therapy). The test meal included white rice (148 g) and a
Fuji apple (150 g). The normal subjects were randomly divided into two
groups: the apple-first group, wherein the subjects consumed white rice 5 min
after consuming the apple, and the rice-first group, wherein the subjects
consumed an apple 5 min after consuming the white rice. Blood samples were
then taken from both groups for 3 h. In addition, the subjects with impaired
glucose tolerance received the same treatment as the normal subjects, with
the difference being glucose level monitoring according to the order in which
the apples were consumed. In the normal subjects, the Cmax of Δblood
glucose and Δinsulin levels were 54.0 ± 5.0 mg/dL and 61.9 ± 7.2 µU/dL
versus 46.2 ± 5.9 mg/dL and 49.8 ± 8.5 µU/dL in the rice-first and apple-first
groups, respectively. The incremental area under the curve (iAUC) of insulin
tended to decrease in the apple-first group. In the impaired glucose tolerance
subjects, the Cmax of Δblood glucose was 75.2 ± 7.2 mg/dL in the apple-first
group compared to 90.0 ± 10.0 mg/dL in the rice-first group, which was a
significant difference (p &lt; 0.05). The iAUC of blood glucose was lower in the
apple-first group. Eating an apple before a meal may be a simple and
effective strategy for managing the glycaemic response in individuals with
impaired glucose tolerance.
14. This study aimed to investigate the possible glycemic effect of apple preload
on acute postprandial glycemic responses (GRs) of a following rice meal,
comparing with its co-ingestion counterpart and an apple sugar solution
preload, based on equal carbohydrates intake. In a randomized crossover trial,
18 healthy female subjects consumed (1) rice, (2) co-ingestion of apple and
rice (A+R), (3) apple preload and rice (PA+R), and (4) rice with sugar solution
preload (same sugar profile as in apple) (PSS+R). Acute postprandial GR tests
and subjective satiety tests were carried out for each test food. Compared
with rice reference, the PA+R achieved a 50% reduction of the iAUC 0-120, a
51.4% reduction of the average peak value, and a 52.6% reduction of glycemic
excursion in 240 min, while the PSS+R showed 29.7% and 31.6% reduction of
peak value and glycemic excursion, respectively. No significant differences
were found between R and PA+R in any of the satiety characteristics.
Compared with rice control, apple preload of 15 g available carbohydrates
remarkably lowered the acute postprandial GR without negative effect on
 satiety. The sugar component may partly contribute to the glycemic
suppressing effect of the apple preload.
15. This study investigated the preload effect of the medium and high glycemic
index (GI) potato, as well as the combination of partially hydrolyzed guar gum
(HG) and potato, when ingested prior to a rice meal, on the iso-carbohydrate
basis. In a randomized crossover trial, 17 healthy female subjects consumed
(1) rice; (2) co-ingestion of highly cooked potato (HP), and rice (HP + R); (3)
co-ingestion of minimally cooked potato (MP) and rice (MP + R); (4) preload
HP prior to rice meal (PHP + R); (5) preload MP prior to rice meal (PMP + R);
(6) co-ingestion of partially hydrolyzed guar gum (HG), HP and rice (HG + HP
+ R); (7) preload HG prior to co-ingestion of HP and rice (PHG + HP + R); (8)
co-preload of HG and HP prior to rice (PHG + PHP + R); and (9) preload of HP
prior to co-ingestion of HG and rice (PHP + HG + R). Postprandial glycemic
response (GR) tests and subjective satiety tests were conducted for each test
food. Cooked potato as a preload to a rice meal could significantly cut the
acute postprandial glycemic excursion by around 1.0 mmol/L, irrespective of
the GI of the preload. Co-preload of partial hydrolyzed guar gum and highly
cooked potato (PHG + PHP + R) resulted in improved acute GR in terms of
peak glucose value and glycemic excursion compared with either HG preload
or HP preload. All the meals with preload showed comparable or improved
self-reported satiety. Within an equicarbohydrate exchange framework, both
high-GI and medium-GI potato preload decreased the postprandial glycemic
excursion in young healthy female subjects. The combination of HG and HP as
double preload resulted in better GR than both single HG or HP preload did.

16. This study aimed to investigate the impact of fruit preloads on the
acute postprandial glycemic response (PGR) and satiety response of a
rice meal in healthy female subjects based on iso-carbohydrate (IC) and
hyper-carbohydrate (HC) contents, respectively. The IC test meals
including (1) rice preload (R + 35R), (2) orange preload (O + 35R), (3)
apple preload (A + 35R) and (4) pear preload (P + 35R), contained 50.0
g available carbohydrates (AC) where the preload contributed 15.0 g
and rice provided 35.0 g. The HC meals included (1) orange preload (O
+ 50R), (2) apple preload (A+50R) and (3) pear preload (P + 50R), each
containing 65.0 g AC, where the fruits contributed 15.0 g and rice
provided 50.0 g. Drinking water 30 min before the rice meal was taken
as reference (W + 50R). All the preload treatments, irrespective of IC or
HC meals, resulted in remarkable reduction (p < 0.001) in terms of
incremental peak glucose (IPG) and the maximum amplitude of
glycemic excursion in 180 min (MAGE0-180), also a significant decrease
(p < 0.05) in the area of PGR contributed by per gram of AC (AAC),
compared with the W + 50R. Apple elicited the lowest PGR among all
test meals, as the A + 35R halved the IPG and slashed the incremental
area under the curve in 180 min (iAUC0-180) by 45.7%, while the A + 50R
 reduced the IPG by 29.7%, compared with the W + 50R. All the preload
meals and the reference meal showed comparable self-reported satiety
in spite of the difference in AC. In conclusion, pre-meal consumption of
three fruits effectively curbed post-meal glycemia even in the case of a
30% extra carbohydrate load.

17. Controlling postprandial glycaemia helps to prevent and manage non-

communicable diseases. One strategy in controlling glycaemia may be to
consume meals in two parts; a preload, followed by the remainder of the
meal. Our aim was to test preloading a rice meal given for breakfast and lunch
on different days, either by splitting the meal (rice preload followed by rice
meal) or by using kiwifruit as a preload compared with consuming the rice
meal in one sitting. Primary outcomes were glycaemic and insulinaemic
responses with secondary outcomes of other hormonal responses, subjective
satiety, and subsequent energy intake. Following breakfast, postprandial
glycaemic peak concentration was 0.9 (95% CI: 0.2, 1.6) mmol/L lower for the
kiwifruit preload compared with the rice meal eaten in one sitting. Following
lunch, glycaemic peak concentrations were 1.0 (0.7, 1.4) and 1.1 (0.5, 1.7)
mmol/L lower for the rice-split and kiwifruit preload compared with the rice
meal alone, respectively. Postprandial insulinaemia area-under-the-curve was
1385 (87, 2684) mU/L·min less for the kiwifruit preload compared with the
rice-split. There were no differences among treatments for subsequent energy
intake. Meal splitting is useful for lowering postprandial glycaemia, and
replacing part of a meal with kiwifruit may help with insulin efficiency without
detriment to subsequent energy intake.
18. he high-protein meals, irrespective of meal frequency were beneficial for
glycaemic health since glucose incremental area under the curve (iAUC) for
PRO-2 (185 ± 166 mmol.min.L(-1)) and PRO-6 (214 ± 188 mmol.min.L(-1))
were 66 and 60 % lower respectively (both p < 0.05), compared with CON-2
(536 ± 290 mmol.min.L(-1)). The iAUC for insulin was the lowest for PRO-6
(13.7 ± 7.1 U.min.L(-1)) as compared with CON-2 (28.4 ± 15.6 U.min.L(-)1), p <
0.001. There were no significant differences in postprandial responses in other
measurements between the dietary treatments.
19. Excess body weight is a major global health concern, particularly due to its
associated increased health risks. Several strategies have been proposed to
prevent overweight and obesity onset. In the past decade, it has been
suggested that eating speed/rate and eating frequency might be related to
obesity. The main aim of this narrative review was to summarize existing
evidence regarding the impact of eating speed/rate and eating frequency on
adiposity, metabolic syndrome (MetS), or diet quality (DQ). For this purpose, a
literature search of observational and interventional trials was conducted
between June and September 2020 in PubMed and Web of Sciences
databases, without any data filters and no limitations for publication date.
Results suggest that children and adults with a faster eating speed/rate may
 be associated with a higher risk of developing adiposity, MetS or its
components. Furthermore, a higher eating frequency could be associated with
diet quality improvement, lower adiposity, and lower risk of developing MetS
or its components. Further interventional trials are warranted to clarify the
mechanism by which these eating behaviors might have a potential impact on
health
20.  In all, 379 youths (13.0 ± 2.8 years; 53% female; BMIz = 0.8 ± 1.1; 22% with
LOC eating) were studied. Anxiety was not significantly related to BMIz,
adiposity, or MetS-related measures. However, anxiety and LOC eating
interacted such that only among youth with LOC eating, anxiety was positively
associated with fasting insulin (p = .02) and insulin resistance (p = .01). The
interaction of anxiety and LOC eating was not significantly related to BMIz,
adiposity, or any other MetS-related measure (ps = ns).
21. Substantial progress has been made in the understanding of anorexia nervosa
(AN) and eating disorder (ED) genetics through the efforts of large-scale
collaborative consortia, yielding the first genome-wide significant loci, AN-
associated genes, and insights into metabo-psychiatric underpinnings of the
disorders. However, the translatability, generalizability, and reach of these
insights are hampered by an overly narrow focus in our research. In particular,
stereotypes, myths, assumptions and misconceptions have resulted in
incomplete or incorrect understandings of ED presentations and trajectories,
and exclusion of certain patient groups from our studies. In this review, we
aim to counteract these historical imbalances. Taking as our starting point the
Academy for Eating Disorders (AED) Truth #5 "Eating disorders affect people
of all genders, ages, races, ethnicities, body shapes and weights, sexual
orientations, and socioeconomic statuses", we discuss what we do and do not
know about the genetic underpinnings of EDs among people in each of these
groups, and suggest strategies to design more inclusive studies. In the second
half of our review, we outline broad strategic goals whereby ED researchers
can expand the diversity, insights, and clinical translatability of their studies.
22. The Western diet increased caloric intake for the first 6 months and body fat,
activity, energy expenditure, insulin resistance, and hepatosteatosis after 2.5
years, whereas the Mediterranean diet reduced triglyceride levels. This is the
first report of differential caloric intake and obesity with long-term
consumption of a Western versus Mediterranean diet under controlled
experimental conditions and the first experimental evidence that a
Mediterranean diet protects against hepatosteatosis compared with a
Western diet.
23. Dietary composition is associated with the differential prevalence of
psychiatric disorders; the Western diet confers increased risk, while the
Mediterranean diet appears to reduce risk. In nonhuman primates, anxiety-
like behaviors and social isolation have been linked to both Western diet
consumption and increased inflammatory disease risk, and recent evidence
suggests that diet composition may affect immune system function in part
through its effects on behavior. This is particularly important in the context of
 the global COVID-19 pandemic in which social isolation has been associated
with disease. Here, we examined the effects of Western- and Mediterranean-
like diets on social behavior in a randomized, 34-month preclinical trial in
middle-aged female cynomolgus macaques (Macaca fascicularis). Diet
induced rapid and persistent changes in a suite of behaviors. After just three
months of experimental diet consumption, a composite measure of diet-
altered behavior (DAB) significantly differed between the two diets (p = 0.014)
and remained different throughout the 24-month experimental observation
period (p = 2.2 × 10-8). Monkeys fed the Western diet spent more time alone
(FDR = 4.4 × 10-5) and displayed more anxiety behavior (FDR = 0.048),
whereas monkeys fed the Mediterranean diet spent more time resting (FDR =
0.0013), attentive (FDR = 0.017), and in body contact with groupmates (FDR =
4.1 × 10-8). These differences were largely due to changes in behavior of
animals fed the Mediterranean diet, while Western-diet-fed-animals exhibited
similar behaviors compared to the eight-month baseline period, during which
all monkeys consumed a common laboratory diet. These observations provide
experimental support in a nonhuman primate model, demonstrating a
potential therapeutic benefit of the Mediterranean diet consumption to
reduce social isolation and anxiety and thus mitigate social isolation-
associated disorders that often accompany illness and disability.
24. Dietary changes associated with industrialization increase the prevalence of
chronic diseases, such as obesity, type II diabetes, and cardiovascular disease.
This relationship is often attributed to an 'evolutionary mismatch' between
human physiology and modern nutritional environments. Western diets
enriched with foods that were scarce throughout human evolutionary history
(e.g. simple sugars and saturated fats) promote inflammation and disease
relative to diets more akin to ancestral human hunter-gatherer diets, such as a
Mediterranean diet. Peripheral blood monocytes, precursors to macrophages
and important mediators of innate immunity and inflammation, are sensitive
to the environment and may represent a critical intermediate in the pathway
linking diet to disease. We evaluated the effects of 15 months of whole diet
manipulations mimicking Western or Mediterranean diet patterns on
monocyte polarization in a well-established model of human health, the
cynomolgus macaque (Macaca fascicularis). Monocyte transcriptional profiles
differed markedly between diets, with 40% of transcripts showing differential
expression (FDR < 0.05). Monocytes from Western diet consumers were
polarized toward a more proinflammatory phenotype. The Western diet
shifted the co-expression of 445 gene pairs, including small RNAs and
transcription factors associated with metabolism and adiposity in humans,
and dramatically altered behavior. For example, Western-fed individuals were
more anxious and less socially integrated. These behavioral changes were also
associated with some of the effects of diet on gene expression, suggesting an
interaction between diet, central nervous system activity, and monocyte gene
expression. This study provides new molecular insights into an evolutionary
 mismatch and uncovers new pathways through which Western diets alter
monocyte polarization toward a proinflammatory phenotype.
25. We found that consumption of a Western diet resulted in significantly higher
mitochondrial respiration with fatty acid oxidation (FAO) (53%), FAO +
complex I (52%), complex I + II (31%), max electron transport system (ETS)
(31%), and ETS rotenone sensitive (31%) than did consumption of a
Mediterranean diet. In addition, measures of respiration in response to fatty
acids were significantly and positively correlated with both insulin resistance
and plasma insulin concentrations.

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