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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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