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PERIODICAL
FASTING AND CALORIC RESTRICTION FOR LIFE EXTENSION,
DISEASE TREATMENT AND CREATIVITY.
(clinical and experimental data)
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| 3.2
FASTING AND CALORIC RESTRICTION PREVENT AND CURE DISEASES
(Evidence) |
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FASTING
AND CALORIC RESTRICTION BENEFIT IN DIABETES |
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EXPERIMENTAL
STUDIES |
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2005
Third Department of Internal
Medicine, First Faculty of Medicine, Charles University,
U nemocnice 1, 128 08 Prague 2, Czech Republic.
Oxidative stress is higher in
obese diabetic than in non-diabetic subjects. This
pilot study evaluates oxidative stress during short-term
administration of a very low calorie diet in obese
persons. Nine obese Type 2 diabetic patients (age
55+/-5 years, BMI 35.9+/-1.9 kg/m2) and nine obese
non-diabetic control subjects (age 52+/-6 years, BMI
37.3+/-2.1 kg/m2) were treated by a very low calorie
diet (600 kcal daily) during 8 days stay in the hospital.
Serum cholesterol, triglycerides, non-esterified fatty
acids (NEFA), beta-hydroxybutyrate (B-HB), ascorbic
acid (AA), alpha-tocopherol (AT), plasma malondialdehyde
(MDA) and superoxide dismutase (SOD) activity in erythrocytes
were measured before and on day 3 and 8 of very low
calorie diet administration. A decrease of serum cholesterol
and triglyceride concentrations on day 8 was associated
with a significant increase of NEFA (0.30+/-0.13 vs.
0.47+/-0.11 micromol/l, p<0.001) and B-HB (0.36+/-.13
vs. 2.23+/-1.00 mmol/l, p<0.001) in controls but
only of B-HB (1.11+/-0.72 vs. 3.02+/-1.95 mmol/l,
p<0.001) in diabetic patients. A significant decrease
of plasma MDA and serum AT together with an increase
of SOD activity and AA concentration (p<0.01) was
observed in control persons, whereas an increase of
SOD activity (p<0.01) was only found in diabetic
patients after one week of the very low calorie diet.
There was a significant correlation between NEFA or
B-HB and SOD activity (p<0.01). We conclude that
one week of a very low calorie diet administration
decreases oxidative stress in obese non-diabetic but
only partly in diabetic persons. Diabetes mellitus
causes a greater resistance to the effects of a low
calorie diet on oxidative stress.
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Abstract The mechanism of the
blood glucose-lowering effect of a 2-day very low
calorie diet (VLCD; 1890 kJ/d) in combination with
the cessation of all blood glucose-lowering agents
was studied in 12 (7 women, 5 men) obese (body mass
index, 36.3 +/- 1.0 kg/m 2 [mean +/- SEM]) type 2
diabetic patients (age, 55 +/- 4 years; HbA 1c , 7.3%
+/- 0.4%) undergoing insulin therapy. Endogenous glucose
production (EGP) and whole body glucose disposal (6,6
2 H 2 -glucose), lipolysis ( 2 H 5 -glycerol), and
substrate oxidation (indirect calorimetry) rates were
measured before and after the intervention in basal
and hyperinsulinemic conditions. After 2 days of a
VLCD and discontinuation of all blood glucose-lowering
therapies, fasting plasma glucose levels did not increase
(11.3 +/- 1.3 vs 10.3 +/- 1.0 mmol/L). Basal EGP significantly
declined (14.2 +/- 1.0 to 11.9 +/- 0.7 mu mol/kg per
minute; P = .009). Basal metabolic clearance rate
of glucose and rate of basal lipolysis did not change.
During hyperinsulinemia, EGP (5.5 +/- 0.8 to 5.2 +/-
0.5 mu mol/kg per minute), whole body glucose disposal
(12.1 +/- 0.7 to 11.3 +/- 1.0 mu mol/kg per minute),
the metabolic clearance rate of glucose, and the rate
of lipolysis did not change after the 2-day intervention.
Cessation of blood glucose-lowering therapy in combination
with a 2-day VLCD does not lead to hyperglycemia and
is associated with a reduction in basal EGP. Insulin-stimulated
whole body glucose disposal did not improve, nor did
insulin suppressibility of EGP and lipolysis.
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Center for Outcomes and Evidence,
Agency for Healthcare, Research and Quality, 540 Gaithers
Road, Room 6325, Rockville, MD, USA, 20850.
BACKGROUND: Most persons with
type 2 diabetes are overweight and obesity worsens
the metabolic and physiologic abnormalities associated
with diabetes. OBJECTIVES: The objective of this review
is to assess the effectiveness of lifestyle and behavioral
weight loss and weight control interventions for adults
with type 2 diabetes. SEARCH STRATEGY: Studies were
obtained from computerized searches of multiple electronic
bibliographic dababases, supplemented with hand searches
of selected journals and consultation with experts
in obesity research. The last search was conducted
May, 2004. SELECTION CRITERIA: Studies were included
if they were published or unpublished randomized controlled
trials in any language, and examined weight loss or
weight control strategies using one or more dietary,
physical activity, or behavioral interventions, with
a follow-up interval of at least 12 months. DATA COLLECTION
AND ANALYSIS: Effects were combined using a random
effects model. MAIN RESULTS: The 22 studies of weight
loss interventions identified had a 4,659 participants
and follow-up of 1 to 5 years. The pooled weight loss
for any intervention in comparison to usual care among
585 subjects was 1.7 kg (95 % confidence interval
[CI] 0.3 to 3.2), or 3.1% of baseline body weight
among 517 subjects. Other main comparisons demonstrated
nonsignificant results: among 126 persons receiving
a physical activity and behavioral intervention, those
who also received a very low calorie diet lost 3.0
kg (95% CI -0.5 to 6.4), or 1.6% of baseline body
weight, more than persons receiving a low-calorie
diet. Among 53 persons receiving identical dietary
and behavioral interventions, those receiving more
intense physical activity interventions lost 3.9 kg
(95% CI -1.9 to 9.7), or 3.6% of baseline body weight,
more than those receiving a less intense or no physical
activity intervention. Comparison groups often achieved
significant weight loss (up to 10.0 kg), minimizing
between-group differences. Changes in glycated hemoglobin
generally corresponded to changes in weight and were
not significant when between-group differences were
examined. No data were identified on quality of life
and mortality. AUTHORS' CONCLUSIONS: Weight loss strategies
using dietary, physical activity, or behavioral interventions
produced small between-group improvements in weight.
These results were minimized by weight loss in the
comparison group, however, and examination of individual
study arms revealed that multicomponent interventions
including very low calorie diets or low calorie diets
may hold promise for achieving weight loss in adults
with type 2 diabetes.
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2004
Center of Diabetes, Endocrine
and Metabolism, Sakura Hospital, School of Medicine,
Toho University, 564-1 Shimoshizu, Sakura-City, Chiba
285-0841, Japan.
The adequate composition of
carbohydrate and fat in low calorie diets for type
2 diabetes mellitus patients with obesity is not fully
established. The aim of this study was to investigate
the effects of low carbohydrate diet on glucose and
lipid metabolism, especially on visceral fat accumulation,
and comparing that of a high carbohydrate diet. Obese
subjects with type 2 diabetes mellitus were randomly
assigned to take a low calorie and low carbohydrate
diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat
= 25:40:35) or a low calorie and high carbohydrate
diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat
= 25:65:10) for 4 weeks. Similar decreases in body
weight and serum glucose levels were observed in both
groups. Fasting serum insulin levels were reduced
in the low carbohydrate diet group compared to the
high carbohydrate diet group (-30% versus -10%, P
< 0.05). Total serum cholesterol and triglyceride
levels decreased in both groups, but were not significantly
different from each other. High-density lipoprotein-cholesterol
(HDL-C) increased in the low carbohydrate diet group
but not in the high carbohydrate diet group (+15%
versus 0%, P < 0.01). There was a larger decrease
in visceral fat area measured by computed tomography
in the low carbohydrate diet group compared to the
high carbohydrate diet group (-40 cm(2) versus -10
cm(2), P < 0.05). The ratio of visceral fat area
to subcutaneous fat area did not change in the high
carbohydrate diet group (from 0.70 to 0.68), but it
decreased significantly in the low carbohydrate diet
group (from 0.69 to 0.47, P < 0.005). These results
suggest that, when restrict diet was made isocaloric,
a low calorie/low carbohydrate diet might be more
effective treatment for a reduction of visceral fat,
improved insulin sensitivity and increased in HDL-C
levels than low calorie/high carbohydrate diet in
obese subjects with type 2 diabetes mellitus.
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Divisions of Diabetes Translation,
National Center for Chronic Disease Prevention and
Health Promotion, Centers for Disease Control and
Prevention, Atlanta, Georgia, USA.
BACKGROUND: Most persons with
type 2 diabetes are overweight, and obesity worsens
the metabolic and physiologic abnormalities associated
with diabetes. Our objective was to assess the effectiveness
of lifestyle and behavioral weight loss and weight
control interventions in adults with type 2 diabetes.
METHODS: Studies were obtained from searches of multiple
electronic bibliographic databases, supplemented with
hand searches of selected journals and consultation
with experts in obesity research. Studies were included
if they were published or unpublished randomized controlled
trials in any language that examined weight loss or
weight control strategies using one or more dietary,
physical activity, or behavioral interventions, with
a follow-up interval of at least 12 months. Effects
were combined using a random-effects model. RESULTS:
The 22 studies of weight loss interventions identified
yielded a total of 4659 participants with a follow-up
of 1 to 5 years. The pooled weight loss for any intervention
in comparison with usual care among 585 subjects was
1.7 kg (95% confidence interval [CI]: 0.3 to 3.2 kg),
or 3.1% of baseline body weight among 511 subjects.
Among 126 persons who underwent a physical activity
and behavioral intervention, those who also received
a very low-calorie diet lost 3.0 kg (95% CI: -0.5
to 6.4 kg), or 1.6% of baseline body weight, more
than persons who received a low-calorie diet. Among
53 persons who received identical dietary and behavioral
interventions, those who received a more intense physical
activity intervention lost 3.9 kg (95% CI: -1.9 to
9.7 kg), or 3.6% of baseline body weight, more than
those who received a less intense or no physical activity
intervention. Comparison groups often achieved substantial
weight loss (up to 10.0 kg), minimizing between-group
differences. Changes in glycated hemoglobin level
generally corresponded to changes in weight and were
not substantial when between-group differences were
examined. CONCLUSION: Weight loss strategies involving
dietary, physical activity, or behavioral interventions
were associated with small between-group improvements
in weight. These results were minimized by weight
loss in the comparison group, however, and examination
of individual study arms revealed that multicomponent
interventions, including very low-calorie diets or
low-calorie diets, may hold promise for achieving
weight loss in adults with type 2 diabetes.
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2001
Wisconsin Regional Primate Research
Center, Madison 53715, USA.
In a longitudinal study of the
effects of moderate (70%) dietary restriction (DR)
on aging, plasma glucose and insulin concentrations
were measured from semiannual, frequently sampled
intravenous glucose tolerance tests (FSIGTT) in 30
adult male rhesus monkeys. FSIGTT data were analyzed
with Bergman's minimal model, and analysis of covariance
revealed that restricted (R) monkeys exhibited increased
insulin sensitivity (S(I), P < 0.001) and plasma glucose
disappearance rate (K(G), P = 0.015), and reduced
fasting plasma insulin (I(b), P < 0.001) and insulin
response to glucose (AIR(G), P = 0.023) compared with
control (C; ad libitum-fed) monkeys. DR reduced the
baseline fasting hyperinsulinemia of two R monkeys,
whereas four C monkeys have maintained from baseline,
or subsequently developed, fasting hyperinsulinemia;
one has progressed to diabetes. Compared with only
the normoinsulinemic C monkeys, R monkeys exhibited
similarly improved FSIGTT and minimal-model parameters.
Thus chronic DR not only has protected against the
development of insulin resistance in aging rhesus
monkeys, but has also improved glucoregulatory parameters
compared with those of otherwise normoinsulinemic
monkeys.
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1999
Bartholin Instituttet, Kommunehospitalet,
Copenhagen, Denmark.
Food intake may be one of several
factors which influence the risk of development of
insulin dependent diabetes mellitus, but the influence
of the pattern of food supply has not been studied
previously. The aim of the present study was to investigate
the effect of intermittent feeding and fasting upon
diabetes in BB rats. This study included three groups.
Group 1 served as control and included 77 animals,
79% became diabetic. In groups 2 and 3, after weaning,
food but not water was withdrawn from the animals:
24 h twice a week in group 2; 24 h every second day
in group 3. Group 2 included 40 BB rats, 50% (p <
0.004) became diabetic. Group 3 included 44 BB rats,
52% (p < 0.01) became diabetic. No differences were
seen between sexes. Degree of insulitis was not influenced
by changed food supply. Regarding blood glucose, no
influence was seen among diabetic animals, among non-diabetic
animals changed food supply reduced blood glucose
values obtained at the end of the study. Intermittent
feeding and fasting tended to reduce mean age at the
time of diagnosis of diabetes, significance was reached
only in female animals from group 3 compared to group
1. Body weight was obtained weekly. Intermittent feeding
and fasting caused a reduced weight gain in group
2 as well as in group 3 compared to control animals;
however, most pronounced in group 3 and also more
pronounced among males compared to females. For pre-diabetic
and non-diabetic animals comparable influence on body
weight was seen. The main conclusion in the study
is that intermittent feeding and fasting reduced diabetes
incidence.
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CLYNICAL
STUDIES |
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2005
Department of Nutritional
Sciences, University of Wisconsin-Madison, USA.
Brief calorie restriction
(CR; 20 days of 60% of ad libitum [AL] intake)
improves insulin-stimulated glucose transport,
concomitant with enhanced phosphorylation of
Akt2. The purpose of this study was to determine
whether Akt2 is essential for the calorie restriction-induced
enhancement in skeletal muscle insulin sensitivity.
We measured insulin-stimulated 2-deoxyglucose
(2DG) uptake in isolated extensor digitorum
longus (EDL) and soleus muscles from male and
female wild-type (WT) and Akt2-null (knockout
[KO]) mice after ad libitum or calorie-restricted
(20 days at 60% of AL) feeding. In WT mice,
calorie restriction significantly enhanced insulin-stimulated
2DG uptake in both muscles regardless of sex.
However, in KO mice, calorie restriction did
not enhance insulin-stimulated 2DG in male or
female EDL or in female soleus. Only in male
KO soleus did calorie restriction significantly
increase insulin-stimulated 2DG through an Akt2-independent
mechanism, although 2DG uptake of the KO-CR
group was reduced compared with the WT-CR soleus
group. Akt2 serine phosphorylation was enhanced
approximately two- to threefold in insulin-stimulated
WT-CR versus WT-AL muscles. Calorie restriction
induced an approximately 1.5- to 2-fold elevation
in Akt1 phosphorylation of insulin-treated muscles,
regardless of genotype, but this increase was
insufficient to replace Akt2 for insulin-stimulated
2DG in Akt2-deficient muscles. These results
indicate that Akt2 is essential for the full
effect of brief calorie restriction on insulin-stimulated
glucose uptake in skeletal muscle with physiologic
insulin .
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2003
School of Medical & Surgical
Sciences, University of Nottingham, and Jenny
O'Neil Diabetes Centre, Southern Derbyshire
Acute Hospitals, NHS Trust, Derby, UK.
AIMS: To evaluate the
short-term and 1-year outcomes of an intensive
very-low-calorie diet (VLCD) on metabolic and
cardiovascular variables in obese patients with
Type 2 diabetes (T2DM) and symptomatic hyperglycaemia
despite combination oral anti-diabetic therapy
+/- insulin, and to assess patient acceptability
and the feasibility of administering VLCD treatment
to this subgroup of patients in a routine practice
setting. METHODS: Forty obese patients with
T2DM (22 M, mean age 52 years, body mass index
(BMI) 40 kg/m2, duration of T2DM 6.1 years)
and symptomatic hyperglycaemia despite combination
oral therapy (n = 26) or insulin + metformin
(n = 14) received 8 weeks of VLCD therapy (750
kcal/day) followed by standard diet and exercise
advice at 2-3-month intervals up to 1 year.
Insulin was discontinued at the start of the
VLCD, and anti-diabetic therapy was adjusted
individually throughout the study, including
(re)commencement of insulin as required. RESULTS:
Immediate improvements in symptoms and early
weight loss reinforced good compliance and patient
satisfaction. After 8 weeks of VLCD, body weight
and BMI had fallen significantly: 119 +/- 19-107
+/- 18 kg and 40.6-36.6 kg/m2, respectively,
with favourable reductions in serum total cholesterol
(5.9-4.9 mm), blood pressure (10/6 mmHg) and
fructosamine (386 +/- 73-346 +/- 49 microm)
(equates to an HbA1c reduction of approximately
1%). Sustained improvements were evident after
1 year, with minimal weight regain, e.g. mean
body weight 109 +/- 18 kg and BMI 37 +/- 4 kg/m2.
Glycaemic control tended to deteriorate after
1 year. CONCLUSIONS: The absence of a control
group is a major limitation, but the results
indicate that 8 weeks of VLCD treatment may
be effective and well tolerated in symptomatic
obese patients with T2DM in secondary failure,
producing sustained cardiovascular and metabolic
improvements after 1 year. VLCD therapy is a
treatment option that deserves greater consideration
in this difficult-to-treat patient population.
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2000
AUTHOR AFFILIATION: Service des
Maladies Metaboliques, Hopital Lapeyronie, Montpellier.
ABSTRACT: It is well-recognized
that standard caloric restrictions (1500 kcal/day)
are usually poorly effective in achieving weight losses
in overweight type 2 diabetic patients. For that reason
very-low-calorie-diets (VLCDs) were developed as a
mean for initiating or accelerating weight reduction.
Short-term studies indicate that VLCDs result generally
in weight losses that are three times greater than
those obtained with standard low-calorie-diets. Fasting
blood glucose values are improving in parallel to
weight losses and in many patients the improvement
in glycemic control is better than that expected from
the magnitude of weight losses. However the results
are rather disappointing after several months or years
of follow-up. For example it has been demonstrated
that weight regain can be observed as soon as the
patient is shifted to a refeeding or maintenance dietary
program at the end of the VLCD period. Long-term results
on glycemic control and body weight reduction are
generally similar with standard low-calorie-diets
and with VLCDs, the final results depending on the
magnitude of weight loss whatever the prescribed diet.
At short-term the VLCDs can be helpful first for initiating
weight losses and second for sensitizing the patient
to the potential benefits of complying to dietary
measures.
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1998
Department of Medicine, CHU Sart
Tilman, Belgium.
Most patients with Type 2 diabetes
are significantly overweight, and diet-induced weight
loss can provide marked improvement in their glycaemic
control. As conventional therapy combining diet and
exercise usually has a poor long-term success rate,
more aggressive weight reduction programmes have been
proposed for the treatment of severely obese diabetic
patients, including very-low-calorie diets, anti-obesity
drugs and bariatric surgery. Very-low-calorie diets
usually have a remarkable short-term effect, and energy
restriction and weight reduction are positive factors
for the glycaemic control of obese diabetic subjects.
However, the long-term efficacy of these methods remains
doubtful since weight regain is a common phenomenon.
Although anti-obesity (anorectic) drugs may help patients
to follow a restricted diet and lose weight, their
overall efficacy on body weight and glycaemia is generally
modest, and their long-term safety still questionable.
Interestingly, serotoninergic anorectic agents have
been shown to improve both the insulin sensitivity
and glycaemic control of obese diabetic patients independently
of weight loss. Bariatric surgery may be helpful in
well-selected patients. The correction of weight excess
after successful gastroplasty fully reverses the abnormalities
of insulin secretion, clearance and action on glucose
metabolism present in markedly obese non-diabetic
patients, and allows interruption or reduction of
insulin therapy and antidiabetic oral agents in most
obese diabetic patients. In conclusion, weight loss
is a major goal in treating obese patients with Type
2 diabetes, and aggressive weight reduction programmes
may be used in selected patients refractory to conventional
diet and drug treatment. However, long-term prospective
studies are needed for more precise determination
of the role of such a strategy in the overall management
of obese diabetic patients.
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