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Diabetes Research and Clinical Practice 65 (2004) 235–241

Beneficial effect of low carbohydrate in low calorie diets on


visceral fat reduction in type 2 diabetic patients with obesity
Yoh Miyashita a , Nobukiyo Koide a , Masaki Ohtsuka a , Hiroshi Ozaki a , Yoshiaki Itoh a ,
Tomokazu Oyama a , Takako Uetake b , Kiyoko Ariga b , Kohji Shirai a,∗
a Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, School of Medicine, Toho University,
564-1 Shimoshizu, Sakura-City, Chiba 285-0841, Japan
b Department of Nutritione, Sakura Hospital, School of Medicine, Toho University, Chiba, Japan

Received 15 March 2003; received in revised form 9 December 2003; accepted 29 January 2004

Abstract

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, es-
pecially 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 cm2 versus −10 cm2 , 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 < 0.05). 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.
© 2004 Elsevier Ireland Ltd. All rights reserved.

Keywords: Low carbohydrate diet; Low calorie diet; Type 2 diabetes mellitus; Obesity; Visceral fat

1. Introduction

The distribution of body fat is known to be im-


∗ Corresponding author. Tel.: +81-43-462-8811; portant in the development of obesity-associated
fax: +81-43-489-9770. metabolic disorders. In particular, accumulation of
E-mail address: kshirai@kb3.so-net.ne.jp (K. Shirai). visceral fat is related to the development of insulin

0168-8227/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.diabres.2004.01.008
236 Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235–241

resistance [1,2] and to a high incidence of coronary 2.2. Diet composition


heart disease [3,4].
A low calorie diet is recognized to be a fundamen- The ratio of the low carbohydrate diet compositions
tal therapy for type 2 diabetic patients with obesity of protein, carbohydrate and fat was 25:39:35 (%), and
to improve insulin sensitivity by weight reduction. A in high carbohydrate diet, the ratio was 26:62:10 (%).
principle of this diet is to provide an adequate amount The ratio of saturated fatty acids, monounsaturated
of proteins, vitamins and minerals, and to restrict car- fatty acids and polyunsaturated fatty acids were 3:4:3
bohydrates and fats as energy components. There have in both diets. Palmitic acid constituted about 70% of
been several reports concerning the role of nutrient the saturated fatty acids, oleic acid about 95% of the
composition of the diet for weight reduction in obe- monounsaturated fatty acids, and a linoleic acid about
sity [5–7]. For example, Rabast et al. [5] reported that 70% of the polyunsaturated fatty acids. The content
low carbohydrate diet is beneficial for weight reduc- of dietary fibers was about 18 g per day in the low
tion, which is associated with low insulin levels and a carbohydrate diet and about 20 g per day in the high
suppression of appetite by ketone body formation. On carbohydrate diet.
the other hand, Yong and Werner et al. reported that
low carbohydrate diet is not always superior to high 2.3. Program of diet therapy
carbohydrate diet for body weight reduction [6,7]. As
a result, there is no definite evidence for appropriate The subjects were initially given a 3 day low calo-
ratio of carbohydrate in low calorie diet. rie diet composed of high carbohydrate (1000 kcal per
Recently, in rats given a normal calorie diet, Zava- day, P:F:C = 26:10:62), after which they were divided
roni and Reaven et al. [8] reported that a diet composed into two random groups. One group of subjects was
of 60% carbohydrates raised glucose levels and de- treated with a low calorie diet composed of low car-
creased insulin sensitivity in rats. Furthermore, Coul- bohydrate (=low carbohydrate diet group, n = 11),
ston and co-workers [9] reported that high carbohy- and the other was treated with a low calorie diet com-
drate diet increased serum glucose, insulin and triglyc- posed of high carbohydrate (=high carbohydrate diet
eride levels, and decreased HDL–C in diabetic pa- group, n = 11). The clinical profile of the subjects
tients. at the start of the different diet therapies is shown in
We have previously reported that low calorie diet Table 1. There were no significant differences between
composed of low carbohydrate is preferable for an im- the two groups. The subjects were treated for 4 weeks
provement of glucose and lipoprotein metabolism in with these diets. During this study, all patients were
type 2 diabetes mellitus patients with obesity [10]. In without medications and treated with exercise therapy
this paper, to clarify whether high or low carbohydrate (walking, 30 min × 2 times per day).
diet is more beneficial for type 2 diabetes mellitus pa-
tients with obesity, the effects of both diets on visceral 2.4. Blood sampling
fat accumulation as well as parameters of glucose and
lipid metabolism were studied. Blood samples were taken in the morning after 12 h
of fasting. Serum was obtained within 1 h and samples
were used for measuring of blood sugar (FBS), insulin
2. Subjects and methods (basal IRI), serum total cholesterol (TC), triglyceride
(TO) and HDL–C.
2.1. Subjects
2.5. Measurement of body weight and total body fat
Twenty-two obese subjects with type 2 diabetes
mellitus patients were recruited for the study (16 Body weight and total body fat were measured in
males, 6 females, mean body mass index 27 kg/m2 ). the morning after 12 h of fasting. The percent body
The mean age was 52.4 ± 13.0 years old. They were fat (%) and lean body mass (LBM) were measured by
all hospitalized and took no medication. All of sub- impedance method using Serkoimpemeter (SIF-93 1,
jects gave informed consent. Serko, Japan).
Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235–241 237

Table 1
Clinical profiles of low carbohydrate diet group or high carbohydrate diet group before treatment
High carbohydrate group (n = 11) Low carbohydrate group (n = 11) Significance

Body mass index 27 ± 2 27 ±4 None


V/S ratioa 0.71 ± 0.8 0.69 ± 0.7 None
HbAlc (%) 9.8 ± 2 10.2 ±2 None
Fasting blood sugar (mg/dl) 200 ± 50 207 ± 36 None
Basal IRI (␮U/ml) 5.9 ± 1.0 6.2 ± 0.9 None
Total cholesterol (mg/dl) 193 ± 48 199 ± 35 None
Triglyceride (mg/dl) 173 ± 60 175 ± 89 None
HDL–C (mg/dl) 39 ± 16 38 ± 10 None
a The ratio of visceral fat area/subcutaneous fat area.

2.6. Measurement of adipose tissue distribution 3. Results

To measure visceral and subcutaneous fat mass, 3.1. Change in the body weight, fat (%) and LBM
computed axial tomography was performed [1]. The
scan was performed at the position of the navel. Vis- In the low carbohydrate and the high carbohydrate
ceral fat area was measured by drawing a line within diet groups, the body weight decreased from 73 to
the muscle wall surrounding the abdominal cavity. The 64 kg, and from 71 to 64 kg, respectively, after low
subcutaneous fat was calculated by subtracting the calorie diet for 4 weeks (Fig. 1A). During these low
amount of visceral fat from the total fat area. From calorie diet therapies, fat (%) decreased in both groups,
these values, a ratio of visceral fat area to subcuta- with no change in LBM in either group (Fig. 1B).
neous fat area (V/S ratio) and an area of visceral fat These changes in body weight, body fat (%) and LBM
was obtained. were not significantly different between the low and
high carbohydrate diet groups (Fig. 1A and B).
2.7. Statistical analysis
3.2. Change in FBS and basal IRI
Statistical analysis was performed using Student’s
t-test and paired t-test. P values less than 0.05 were In low carbohydrate and high carbohydrate diet
considered significant. groups, FBS decreased from 207 to 104 mg/dl, and

Fig. 1. Changes in body weight, body fat (%) and lean body mass during low calorie diets in low carbohydrate diet group (䊉) and high
carbohydrate diet group (䊊). (A–C) Show changes of body weight, body fat (%), and lean body mass, respectively. Data are shown as
mean ± S.D.
238 Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235–241

no significant difference was observed between both


groups (Fig. 4A and B).
HDL–C was significantly increased in the low car-
bohydrate diet group compared to the high carbohy-
drate diet group (Fig. 4C).

3.4. The change in visceral fat, and V/S ratio

In the low carbohydrate diet group, the amount of


visceral fat area was significantly decreased from 124
to 84 cm2 (P < 0.05) after 4 weeks of diet, and V/S
ratio decreased from 0.47 to 0.69 (P < 0.05) during
the same period (Fig. 5A and B). In contrast, neither
Fig. 2. Effect of the low carbohydrate diet (䊉) and the high car-
bohydrate diet (䊊) on fasting blood glucose levels. Fasting blood
the amount of visceral fat area or V/S ratio changed
glucose levels were decreased in both groups with no significant significantly during diet in the high carbohydrate diet
difference between the two groups. Data are shown as mean±S.D. group (Fig. 5A and B).

from 200 to 102 mg/dl, respectively after low calorie 4. Discussion


diet for 4 weeks. There was no significant difference
between two groups (Fig. 2). In this study, we have shown for the first time a dif-
Basal IRI showed a larger decrease in low carbo- ference in effects of two low calorie diets with low
hydrate diet group compared to the high carbohydrate or high carbohydrate content on visceral fat loss and
diet group (Fig. 3A). The decreasing rate of basal IRI serum insulin levels in obese patients with type 2 di-
was significantly high in low carbohydrate diet group abetes.
compared to high carbohydrate group (Fig. 3B). During both diet therapies, the body weights were
decreased without a decrease in LBM, and FBS lev-
3.3. Change in serum lipids els decreased as well as TC and TG levels. However,
although the decrease in FBS were similar between
TC and TG were decreased by about 20%, and the high and low carbohydrate diet groups, basal IRI
40–50% in low carbohydrate diet group and high levels were significantly lower in the low carbohy-
carbohydrate diet group during low calorie diet, but drate diet group compared to the high carbohydrate

Fig. 3. Changes in IRI during low calorie diets in low carbohydrate diet group (closed circle and solid bar) and high carbohydrate diet
(open circle and open bar). (A and B) Show change and ratio of decrease of basal IRI. Data are shown as mean ± S.D., ∗ P < 0.05.
Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235–241 239

Fig. 4. Changes in serum lipids during low calorie diets in low carbohydrate diet group (䊉) and high carbohydrate diet group (䊊). (A–C)
Show changes of total cholesterol, triglyceride and HDL–C. Data are shown as mean ± S.D, ∗ P < 0.05 and ∗∗ P < 0.01.

diet group at the end of the study. The lower lev- HDL–C levels were also significantly increased af-
els of insulin with similar levels of blood glucose ter 4 weeks diet in the low carbohydrate diet group
indicate a larger improvement of insulin sensitivity compared with the high carbohydrate diet group but
in the low carbohydrate diet group. The homeostasis there were no differences in the reduction of TC or
model assessment-ratio [11] of the low carbohydrate TO between the two groups. It is known that one of
diet group and the high carbohydrate diet group were mechanisms by which the HDL–C is increased is by
changed from 3.06 to 0.77, and from 2.96 to 1.21, re- enhanced catabolism of very low-density lipoproteins
spectively (data not shown). [12]. Accordingly, it is possible that a diet low in
240 Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235–241

Fig. 5. Changes in adipose tissue distribution measured by computed tomography after low calorie diets for a month in low carbohydrate
diet group (䊉) and high carbohydrate diet group (䊊). (A and B) Show changes of visceral fat and V/S ratio. Data are shown as mean ±S.D.,
∗ P < 0.05.

carbohydrates could stimulate the catabolism of very [19,20]. Consequently, the levels of free fatty acids
low-density lipoproteins. Another possibility is that may be important factor during diet therapy. Free fatty
the activity of lipoprotein lipase might be improved, acids would be expected to increase during a low calo-
accompanying with the increased insulin sensitivity rie diet due to an increased fat mobilization. In our
[13,14]. study, the homeostasis model assessment-ratio in the
There were also differences in the effect on adi- low carbohydrate diet is better compared to that in
pose tissue distribution between the two groups. In the high carbohydrate diet. Hence, increased free fatty
low carbohydrate diet group, the visceral fat area and acid levels during weight reduction by low calorie/low
the V/S ratio were significantly decreased during diet, carbohydrate diet did not deteriorate the insulin sensi-
but not in high carbohydrate diet group. As for the tivity in these subjects. Furthermore, Reaven reported
mechanisms, there are at least two possible explana- that high carbohydrate intake would tend to increase
tions. The first is that the low carbohydrate diet could the risk of vascular complications [21,22], and high
stimulate growth hormone secretion from the pituitary carbohydrate diet is reported to increase blood glu-
gland [15]. This could explain the different effects of cose, insulin, and TG levels and decrease HDL–C in
the two diets on visceral fat mass since it has previ- diabetes mellitus patients [9]. In agreement with this,
ously been shown that the lipolytic activity induced by our data suggest that a high carbohydrate intake would
growth hormone is higher in visceral fat compared to not always be beneficial. In our study, the amount of
subcutaneous fat [16,17]. Consequently, in this study, total intake of fat in the low carbohydrate diet was
the secretion of growth hormone might be enhanced about 40 g per day, which is not considered to be an
to a larger extent by the low carbohydrate diet com- excessive fat intake, and is equal to that of 1600 kcal in
pared to the high carbohydrate diet. Another possibil- a high carbohydrate diet that is widely recommended.
ity is a lower insulin requirement of the low carbohy- Consequently, our data suggest that the more favor-
drate diet. Hyperinsulinemia is reported to be associ- able effect on metabolism induced by the low carbo-
ated with visceral fat [1,2] and a high level of fasting hydrate diet compared to the high carbohydrate diet
insulin is reported to predict visceral fat accumulation would be not due to be over-intake of fat, but rather
[18]. In our study, there was a larger decrease of basal restriction of carbohydrate.
IRI by the low carbohydrate diet compared to the high It is known that monounsaturated fatty acids is
carbohydrate diet. Accordingly, low insulin secretion preferable to saturated fatty acids for the diet therapy
in low carbohydrate diet might be beneficial for re- of type 2 diabetes mellitus patients [23,24]. Reaven
duction of visceral fat accumulation. also reported that substituting monounsaturated fats
Bjorntorp and co-workers reported that an increased for carbohydrates might be advantageous in reducing
flux of free fatty acids could cause insulin resistance the long-term complications, particularly coronary
Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235–241 241

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