Miyashita Paper

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Diabetes Research and Clinical Practice 65 (2004) 235241

Beneficial effect of low carbohydrate in low calorie diets onvisceral fat reduction in type 2 diabetic patients with obesity

Yoh Miyashita a, Nobukiyo Koide a, Masaki Ohtsukaa, Hiroshi Ozaki a, Yoshiaki Itoh a,

Tomokazu Oyamaa

, Takako Uetakeb

, Kiyoko Arigab

, Kohji Shiraia,

a Center of Diabetes, Endocrine and Metabolism, Sakura Hospital, School of Medicine, Toho University,

564-1 Shimoshizu, Sakura-City, Chiba 285-0841, Japanb 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 aimof this study was to investigate theeffectsof lowcarbohydrate diet on glucose andlipid metabolism, es-

pecially on visceral fat accumulation, andcomparing 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% versus10%, P < 0.05).

Total serum cholesterol and triglyceride levels decreased in both groups, but were not significantly different from each other.

High-density lipoproteincholesterol (HDLC) 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 (40cm2 versus 10cm2, 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 HDLC 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

Corresponding author. Tel.: +81-43-462-8811;

fax: +81-43-489-9770.

E-mail address: [email protected] (K. Shirai).

1. Introduction

The distribution of body fat is known to be im-

portant in the development of obesity-associated

metabolic disorders. In particular, accumulation of

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


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236 Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235241

resistance [1,2] and to a high incidence of coronaryheart disease [3,4].

A low calorie diet is recognized to be a fundamen-

tal therapy for type 2 diabetic patients with obesity

to improve insulin sensitivity by weight reduction. A

principle of this diet is to provide an adequate amount

of proteins, vitamins and minerals, and to restrict car-

bohydrates and fats as energy components. There have

been several reports concerning the role of nutrient

composition of the diet for weight reduction in obe-

sity [57]. For example, Rabast et al. [5] reported that

low carbohydrate diet is beneficial for weight reduc-

tion, which is associated with low insulin levels and a

suppression of appetite by ketone body formation. On

the other hand, Yong and Werner et al. reported that

low carbohydrate diet is not always superior to high

carbohydrate diet for body weight reduction [6,7]. As

a result, there is no definite evidence for appropriate

ratio of carbohydrate in low calorie diet.

Recently, in rats given a normal calorie diet, Zava-

roni and Reaven et al. [8] reported that a diet composed

of 60% carbohydrates raised glucose levels and de-

creased insulin sensitivity in rats. Furthermore, Coul-

ston and co-workers [9] reported that high carbohy-

drate diet increased serum glucose, insulin and triglyc-

eride levels, and decreased HDLC in diabetic pa-tients.

We have previously reported that low calorie diet

composed of low carbohydrate is preferable for an im-

provement of glucose and lipoprotein metabolism in

type 2 diabetes mellitus patients with obesity [10]. In

this paper, to clarify whether high or low carbohydrate

diet is more beneficial for type 2 diabetes mellitus pa-

tients with obesity, the effects of both diets on visceral

fat accumulation as well as parameters of glucose and

lipid metabolism were studied.

2. Subjects and methods

2.1. Subjects

Twenty-two obese subjects with type 2 diabetes

mellitus patients were recruited for the study (16

males, 6 females, mean body mass index 27 kg/m2).

The mean age was 52.4 13.0 years old. They were

all hospitalized and took no medication. All of sub-

jects gave informed consent.

2.2. Diet composition

The ratio of the low carbohydrate diet compositions

of protein, carbohydrate and fat was 25:39:35 (%), and

in high carbohydrate diet, the ratio was 26:62:10 (%).

The ratio of saturated fatty acids, monounsaturated

fatty acids and polyunsaturated fatty acids were 3:4:3

in both diets. Palmitic acid constituted about 70% of

the saturated fatty acids, oleic acid about 95% of the

monounsaturated fatty acids, and a linoleic acid about

70% of the polyunsaturated fatty acids. The content

of dietary fibers was about 18 g per day in the low

carbohydrate diet and about 20 g per day in the high

carbohydrate diet.

2.3. Program of diet therapy

The subjects were initially given a 3 day low calo-

rie diet composed of high carbohydrate (1000 kcal per

day, P:F:C = 26:10:62), after which they were divided

into two random groups. One group of subjects was

treated with a low calorie diet composed of low car-

bohydrate (=low carbohydrate diet group, n = 11),

and the other was treated with a low calorie diet com-

posed of high carbohydrate (=high carbohydrate diet

group, n = 11). The clinical profile of the subjectsat the start of the different diet therapies is shown in

Table 1. There were no significant differences between

the two groups. The subjects were treated for 4 weeks

with these diets. During this study, all patients were

without medications and treated with exercise therapy

(walking, 30 min 2 times per day).

2.4. Blood sampling

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(basal IRI), serum total cholesterol (TC), triglyceride

(TO) and HDLC.

2.5. Measurement of body weight and total body fat

Body weight and total body fat were measured in

the morning after 12 h of fasting. The percent body

fat (%) and lean body mass (LBM) were measured by

impedance method using Serkoimpemeter (SIF-93 1,

Serko, Japan).


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Y. Miyashita et al. / Diabetes Research and Clinical Practice 65 (2004) 235241 237

Table 1Clinical 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

HDLC (mg/dl) 39 16 38 10 None

a The ratio of visceral fat area/subcutaneous fat area.

2.6. Measurement of adipose tissue distribution

To measure visceral and subcutaneous fat mass,

computed axial tomography was performed [1]. The

scan was performed at the position of the navel. Vis-

ceral fat area was measured by drawing a line within

the muscle wall surrounding the abdominal cavity. The

subcutaneous fat was calculated by subtracting the

amount of visceral fat from the total fat area. From

these values, a ratio of visceral fat area to subcuta-

neous fat area (V/S ratio) and an area of visceral fat

was obtained.

2.7. Statistical analysis

Statistical analysis was performed using Students

t-test and paired t-test. P values less than 0.05 were

considered significant.

Fig. 1. Changes in body weight, body fat (%) and lean body mass during low calorie diets in low carbohydrate diet group ( ) and high

carbohydrate diet group (). (AC) Show changes of body weight, body fat (%), and lean body mass, respectively. Data are shown as

mean S.D.

3. Results

3.1. Change in the body weight, fat (%) and LBM

In the low carbohydrate and the high carbohydrate

diet groups, the body weight decreased from 73 to

64 kg, and from 71 to 64 kg, respectively, after low

calorie diet for 4 weeks (Fig. 1A). During these low

calorie diet therapies, fat (%) decreased in both groups,

with no change in LBM in either group (Fig. 1B).

These changes in body weight, body fat (%) and LBM

were not significantly different between the low and

high carbohydrate diet groups (Fig. 1A and B).

3.2. Change in FBS and basal IRI

In low carbohydrate and high carbohydrate diet

groups, FBS decreased from 207 to 104 mg/dl, and


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Fig. 2. Effect of the low carbohydrate diet () and the high car-bohydrate diet () on fasting blood glucose levels. Fasting blood

glucose levels were decreased in both groups with no significant

difference between the two groups. Data are shown as meanS.D.

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

diet for 4 weeks. There was no significant difference

between two groups (Fig. 2).

Basal IRI showed a larger decrease in low carbo-

hydrate diet group compared to the high carbohydrate

diet group (Fig. 3A). The decreasing rate of basal IRI

was significantly high in low carbohydrate diet group

compared to high carbohydrate group (Fig. 3B).

3.3. Change in serum lipids

TC and TG were decreased by about 20%, and

4050% in low carbohydrate diet group and high

carbohydrate diet group during low calorie diet, but

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.

no significant difference was observed between bothgroups (Fig. 4A and B).

HDLC 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

the amount of visceral fat area or V/S ratio changed

significantly during diet in the high carbohydrate diet

group (Fig. 5A and B).

4. Discussion

In this study, we have shown for the first time a dif-

ference in effects of two low calorie diets with low

or high carbohydrate content on visceral fat loss and

serum insulin levels in obese patients with type 2 di-

abetes.

During both diet therapies, the body weights weredecreased without a decrease in LBM, and FBS lev-

els decreased as well as TC and TG levels. However,

although the decrease in FBS were similar between

the high and low carbohydrate diet groups, basal IRI

levels were significantly lower in the low carbohy-

drate diet group compared to the high carbohydrate


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Fig. 4. Changes in serum lipids during low calorie diets in low carbohydrate diet group (

) and high carbohydrate diet group (

). (AC)Show changes of total cholesterol, triglyceride and HDLC. 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-

els of insulin with similar levels of blood glucose

indicate a larger improvement of insulin sensitivity

in the low carbohydrate diet group. The homeostasis

model assessment-ratio [11] of the low carbohydrate

diet group and the high carbohydrate diet group were

changed from 3.06 to 0.77, and from 2.96 to 1.21, re-

spectively (data not shown).

HDLC levels were also significantly increased af-

ter 4 weeks diet in the low carbohydrate diet group

compared with the high carbohydrate diet group but

there were no differences in the reduction of TC or

TO between the two groups. It is known that one of

mechanisms by which the HDLC is increased is by

enhanced catabolism of very low-density lipoproteins

[12]. Accordingly, it is possible that a diet low in


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

carbohydrates could stimulate the catabolism of very

low-density lipoproteins. Another possibility is that

the activity of lipoprotein lipase might be improved,

accompanying with the increased insulin sensitivity

[13,14].

There were also differences in the effect on adi-

pose tissue distribution between the two groups. In

low carbohydrate diet group, the visceral fat area and

the V/S ratio were significantly decreased during diet,

but not in high carbohydrate diet group. As for themechanisms, there are at least two possible explana-

tions. The first is that the low carbohydrate diet could

stimulate growth hormone secretion from the pituitary

gland [15]. This could explain the different effects of

the two diets on visceral fat mass since it has previ-

ously been shown that the lipolytic activity induced by

growth hormone is higher in visceral fat compared to

subcutaneous fat [16,17]. Consequently, in this study,

the secretion of growth hormone might be enhanced

to a larger extent by the low carbohydrate diet com-

pared to the high carbohydrate diet. Another possibil-

ity is a lower insulin requirement of the low carbohy-drate diet. Hyperinsulinemia is reported to be associ-

ated with visceral fat [1,2] and a high level of fasting

insulin is reported to predict visceral fat accumulation

[18]. In our study, there was a larger decrease of basal

IRI by the low carbohydrate diet compared to the high

carbohydrate diet. Accordingly, low insulin secretion

in low carbohydrate diet might be beneficial for re-

duction of visceral fat accumulation.

Bjorntorp and co-workers reported that an increased

flux of free fatty acids could cause insulin resistance

[19,20]. Consequently, the levels of free fatty acids

may be important factor during diet therapy. Free fatty

acids would be expected to increase during a low calo-

rie diet due to an increased fat mobilization. In our

study, the homeostasis model assessment-ratio in the

low carbohydrate diet is better compared to that in

the high carbohydrate diet. Hence, increased free fatty

acid levels during weight reduction by low calorie/low

carbohydrate diet did not deteriorate the insulin sensi-

tivity in these subjects. Furthermore, Reaven reportedthat high carbohydrate intake would tend to increase

the risk of vascular complications [21,22], and high

carbohydrate diet is reported to increase blood glu-

cose, insulin, and TG levels and decrease HDLC in

diabetes mellitus patients [9]. In agreement with this,

our data suggest that a high carbohydrate intake would

not always be beneficial. In our study, the amount of

total intake of fat in the low carbohydrate diet was

about 40 g per day, which is not considered to be an

excessive fat intake, and is equal to that of 1600 kcal in

a high carbohydrate diet that is widely recommended.

Consequently, our data suggest that the more favor-able effect on metabolism induced by the low carbo-

hydrate diet compared to the high carbohydrate diet

would be not due to be over-intake of fat, but rather

restriction of carbohydrate.

It is known that monounsaturated fatty acids is

preferable to saturated fatty acids for the diet therapy

of type 2 diabetes mellitus patients [23,24]. Reaven

also reported that substituting monounsaturated fats

for carbohydrates might be advantageous in reducing

the long-term complications, particularly coronary


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heart disease, in type 2 diabetes mellitus patients [9].In our study, intake of monounsaturated fats was not

always high, but low carbohydrate diet was more

beneficial than high carbohydrate diet for glucose and

lipid metabolism in type 2 diabetes mellitus. Further

studies regarding fat composition are required.

In summary, it is concluded that for type 2 diabetes

mellitus patients with obesity, low carbohydrate con-

tent in the low calorie diet showed more favorable ef-

fects on reducing visceral fat, lower serum insulin lev-

els and improving serum lipid levels compared to an

iso-caloric high carbohydrate diet.

Acknowledgements

This study is supported partly by a fund from the

Meeting of Obesity and Nutritional Disturbance.

References

[1] S. Yamashita, T. Nakamura, I. Shimomura, M. Nishida, S.

Yoshida, K. Kotani, K. Kameda, K. Tokunaga, Y. Maatsuzawa,

Insulin resistance and body fat distribution, Diab. Care 19

(1996) 287291.

[2] D.J. Evans, R.G. Hoffman, R.K. Kalkhoff, A.H. Kissebah,

Relationship of body fat topography to insulin sensitivity and

metabolic profiles in premenopausal women, Metabolism 33

(1984) 6875.

[3] P. Ducimetire, J. Richard, F. Cambien, The pattern of

subcutaneous fat distribution in middle-aged men and the risk

of coronary heart disease: the Paris Prospective Study, Int. J.

Obes. 10 (1986) 229240.

[4] R.P. Donahue, R.D. Abbott, E. Bloom, D.M. Reed, K. Yano,

Central obesity and coronary heart disease in men, Lancet 4

(1987) 821824.

[5] U. Rabast, J. Schonbrn, H. Kasper, Diabetic treatment of

obesity with low and high-carbohydrate diets: comparative

studies and clinical results, Int. J. Obes. 3 (1979) 201211.

[6] M.U. Yang, V. Itallie, Composition of weight loss duringshort-term weight reduction, J. Clin. Invest. 58 (1976) 722

730.

[7] S.B. Werner, Comparison between weight reduction on a high

calorie high fat diet and on an isocaloric regimen high in

carbohydrate, N. Eng. J. Med. 66 (1955) 252.

[8] I. Zavaroni, Y.D. Chen, G.M. Reaven, Studies of the

mechanism of fructose-induced hypertriglyceridemia in the

rat, Metabolism 31 (1982) 10771083.

[9] A. Garg, J.P. Bantle, R.R. Henry, A.M. Coulston, K.A. Griver,

B.A. Huet, G.M. Reaven, Effects of varying carbohydrate

content of diet in patients with non-insulin-dependent diabetes

mellitus, JAMA 271 (1994) 14211428.

[10] Y. Miyashita, Y. Itoh, S. Hashiguchi, M. Totsuka, T. Murano,K. Ariga, T. Uetake, C. Nagai, H. Tomioka, K. Shirai, Effects

of low carbohydrate content of low calory diet for obese

non-insulin-dependent diabetes mellitus patients on glucose

and lipid metabolism, J. Jpn. Diab. Soc. 41 (1998) 885890.

[11] R.C. Turner, R.R. Holman, D. Matthews, T.D. Hockaday, J.

Peto, Insulin deficiency and insulin resistance interaction in

diabetes: estimation of their relative contribution by feedback

analysis from basal plasma insulin and glucose concentrations,

Metabolism 11 (1979) 10861096.

[12] B. Staels, J. Dallongeville, J. Auwerx, K. Schoonjans, E.

Leitersdorf, J.C. Fruchart, Mechanism of action of fibrates

on lipid and lipoprotein metabolism, Circulation 19 (1998)

20882093.

[13] J.R. Mead, S.A. Irvine, D.P. Ramji, Lipoprotein lipase:

structure, function, regulation, and role in disease, J. Mol.Med. 80 (2002) 753769.

[14] L.K. Pulawa, R.H. Eckel, Over expression of muscle

lipoprotein lipase and insulin sensitivity, Curr. Opin. Clin.

Nutr. Metab. Care 5 (2002) 569574.

[15] J.L. Langfort, R. Zarzeczny, K. Nazar, H. Kaciuba-Uscilko,

The effect of low-carbohydrate diet on the pattern of hormonal

changes during incremental, graded exercise in young men,

Int. J. Sport Nutr. Exerc. Metab. 11 (2001) 248257.

[16] Y. Itoh, K. Shiai, Preferential lipolysis in rat visceral adipose

tissues by growth hormone, Endocrinol. Metab. 4 (1997) 61

67.

[17] P. Lucidi, N. Parlanti, F. Piccioni, F. Snateusanio, P. De

Feo, Short-term treatment with low doses of recombinant

human GH stimulates lipolysis in visceral obese men, J. Clin.

Endocrinol. Metab. 87 (2002) 31053109.[18] E.J. Boyko, D.L. Leonetti, R.W. Bergstrom, L. Newell-Morris,

W.Y. Fujimoto, Low insulin secretion and high fasting

insulin and C-peptide levels predict increased visceral

adiposity. %-year follow-up among initially nondiabetic

Japanese-American men, Diabetes 45 (1996) 10101015.

[19] M. Rebuffe-Scrive, B. Anderson, L. Olbe, P. Bjorntorp,

Metabolism of adipose tissue in intraabdominal deposits in

severely obese men and women, Metabolism 39 (1990) 570

574.

[20] J. Svedberg, P. Bjomtorp, U. Smith, P. Lonnroth, Free-fatty

acid inhibition of insulin binding, degradation, and action in

isolated rat hepatocytes, Diabetes 39 (1990) 570574.

[21] G.M. Reaven, The role of insulin resistance and

hyperinsulinemia in coronary heart disease, Metabolism 41

(1992) 1619.[22] R.W. Stout, Insulin and atheroma: 20-year perspective, Diab.

Care 13 (1990) 631654.

[23] A. Gang, A. Bonanome, S.M. Grundy, Z.J. Zhang, R.H.

Unger, Comparison of a high-carbohydrate diet with a

high-monounsaturated-fat diet in patients with non-insulin-

dependent diabetes mellitus, N. Engl. J. Med. 319 (1988)

829834.

[24] M. Parillo, A.A. Rivellese, A.V. Ciardullo, A high-monoun-

saturated-fat/low-carbohydrate diet improves peripheral

insulin sensitivity in non-insulin-dependent diabetic patients,

Metabolism 41 (1992) 13731378.

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