![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
2
Department of Health Management, Koshien University, Graduate School of Nutrition, Takarazuka, Hyogo, 665-0006 Japan;
*
Department of Internal Medicine, Itami City Hospital, Itami, Hyogo, 664-8540 Japan; and
Biological Science Laboratories, Kao Corporation, Ichikai-machi, Haga-gun, Tochigi, 321-3497 Japan
2To whom correspondence should be addressed. E-mail: 384895{at}kastanet.kao.co.jp
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
KEY WORDS: • diacylglycerol • triacylglycerol • humans • diabetes • hypertriglyceridemia
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
), and moderate hypertriglyceridemia persists even after satisfactory blood sugar control in patients with hypertriglyceridemia complicated by diabetes (2
). We have encountered a large number of diabetics with hypertriglyceridemia whose blood sugar levels are well controlled by receiving continuous nutritional counseling at the outpatient clinic, yet who continue to have high serum triacylglycerol (TG) 3
concentrations.
Large-scale epidemiologic studies indicate that improvement of hypertriglyceridemia can prevent arteriosclerotic diseases (3
,4
). Thus, treatment of hypertriglyceridemia in diabetic patients is an important issue. Dietary recommendations include consumption of less fat and carbohydrate and more dietary fiber. Nutritional counseling and increased dietary fiber intake, however, have not had sufficient beneficial effects in our patients. Therefore, we have attempted a diet therapy using a diacylglycerol (DG) oil whose beneficial effects on lipid metabolism have been recently reported (5
,6
).
DG is a natural component of various edible oils (7
,8
), and a cooking oil containing >80 g DG/100 g has been approved as a "Food for Specified Health Use" by the Ministry of Health and Welfare, the former name of the Ministry of Health, Labor and Welfare in Japan. Compared with TG oil, long-term consumption of DG oil is claimed to lower the postprandial elevation of serum TG concentration and to suppress body fat accumulation.
Studies have suggested that DG, mainly in the 1,3-isoform, has metabolic characteristics distinct from TG, which may prevent postprandial lipidemia (5
) and body fat accumulation (6
) in healthy humans. In addition, in controlled feeding studies, DG has been shown to prevent the accumulation of body weight and fat associated with a high fat and sucrose diet in obesity- and diabetes-prone mice (9
).
In the present study, we examined the influence of long-term ingestion of DG on blood lipids in type II diabetics with hypertriglyceridemia.
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
The randomized, single-blind, controlled parallel trial was conducted at the Itami City Hospital, Itami, Japan. Potential subjects were screened at the clinic visit. This study with human volunteers was carried out with sufficient respect for the spirit of the Helsinki Declaration of 1975 as revised in 1983. The procedures were fully explained to the volunteers. All subjects gave their signed informed consent before admission.
The subjects were 16 diabetic patients with a mean body mass index (BMI) of 26.3 ± 2.9 kg/m2. They were randomly assigned to the DG group (n = 8) in which an ordinary cooking oil (TG oil) was switched to DG oil (target dose, 10 g/d) or to the control group (n = 8) in which consumption of the ordinary cooking oil was continued. For both groups, the study period was 12 wk. The DG group consisted of 3 men and 5 women with a mean age of 56.8 ± 7.3 y; the control group consisted of 4 men and 4 women with a mean age of 54.1 ± 18.8 y. Five patients in the DG group and six patients in the control group had been treated only with nutritional counseling. Three in the DG group had been treated with medicine to control blood glucose (1 with sulfonylurea, 1 with an 
-glucosidase inhibitor, 1 with insulin). Two in the control group had been treated with medicines (1 with sulfonylurea, 1 with an -glucosidase inhibitor). These patients did not smoke.
During nutritional counseling, the patients had been advised to consume less total energy and alcohol, and to consume dietary fiber and fats containing (n-3) fatty acids. The ratio of (n-6)/(n-3) fatty acids at the beginning of the study was 4.5 and 4.4 for the DG and the control group, respectively. The number of patients who consumed alcohol regularly had been decreased by the counseling from 5 of 16 to 2 of 16. The amount of alcohol consumption by the two patients had also been decreased to 16–23 g/d. Serum TG levels of these patients were persistently elevated despite the advise given at the outpatient clinic for a period of 14.4 ± 12.7 mo.
Test products.
The test oils used in this study were cooking oils commercially available in Japan. Healthy Econa Cooking Oil (Kao, Tokyo, Japan) which was approved as a Food for Specified Health Use in Japan by the Ministry of Health and Welfare (May 20, 1998
), was used as the DG oil. The DG content of this cooking oil is 
80 g DG/100 g. The DG oil and control TG oil contained oleic acid and linoleic acid as the major fatty acids with minor components similar to those reported previously (6
). These test oils were used for cooking, such as for frying food, and for homemade dressing.
Dietary record.
The subjects were instructed to record daily meals and snacks in a dietary diary for 4 consecutive days at the beginning and at the end of the test period. At the clinic visit, a dietitian reviewed the food diaries and recorded their meals after clarifying results with patient interviews. Means of daily intakes of energy, fat and cooking oil were calculated from the food record by a dietitian on the basis of the 4th Revision of the Standard Tables of Food Composition in Japan (10
). The DG intake was estimated from the amount of DG oil ingested and the content of DG in the DG oil (80 g/100 g).
Blood sampling and analyses.
During wk 0 and 12, blood samples were collected from fasting subjects. Blood sampling and anthropometric measurements were performed on the same day. The subjects were deprived of food overnight from 2100 h; a venous blood sample was obtained between 0900 and 1000 h the next day. All of the analyses, except the glucose, were performed with serum samples. For glucose determination, plasma was prepared from blood samples collected in tubes containing EDTA. Plasma and serum were obtained by centrifugation at 1500 x g for 15 min at 4°C. Serum TG concentration was measured using an enzymatic assay kit (Triglyceride E-HR; Wako Pure Chemicals, Osaka, Japan), which is negligibly affected by ascorbic acid and bilirubin in samples. Total cholesterol concentration was determined using an enzymatic assay kit (Quick-Auto-Neo T-CHO-II; Shino-Test, Tokyo, Japan). HDL cholesterol was determined using an assay kit (Determiner L HDL-C, Kyowa Medex, Tokyo, Japan). Glucose concentration was determined using a glucose-dehydrogenase assay kit (Merck Liquid GLU, Kanto Chemicals, Tokyo, Japan). Glycohemoglobin A1c (HbA1c) was measured by an automated HPLC assay as described previously (11
).
Statistical analyses.
Values were expressed as means ± SD. A paired t test was used when there was a regular distribution of the data. When the distribution was not regular, Wilcoxon’s test (coded rank sum for small samples) was performed. The significance of intergroup differences or intragroup changes in serum TG levels was tested after log transformation. Differences were considered significant when P < 0.05.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
. No significant changes from the initial values in body weight, BMI, energy intake, percentage of energy from fat, total fat intake and total cooking oil intake were found in either group. Energy intake was apparently underreported because the energy values reported were less than those required to maintain the body weight of the subjects. Nevertheless, the values did not change during the study period. Fat intake in both groups did not exceed the mean fat intake (57.9 g/d) for the Japanese, as reported in the National Nutrition Survey in 1998 (12
). Although there were no changes during the test period in either group, the percentage of energy from fat exceeded the target value (20–25%) of the Recommended Daily Allowances of Nutrition for the Japanese People (13
). In the DG group, DG intake markedly increased (P < 0.001) and TG intake concomitantly decreased. In the control group, on the other hand, TG intake did not change throughout the study (Table 1)
.
|
), and these concentrations did not change during the experiment in the control group. The serum TG level in the DG group, in contrast, decreased (P < 0.01; Table 2
) and the groups differed at 12 wk (P < 0.05).
|
. In the DG group, the HbA1c level decreased 9.7% (P < 0.05). At 12 wk, the HbA1c levels of the two groups tended to differ (P = 0.07). The normal range of HbA1c established by the Japan Diabetes Society is 4.3–5.8% (14
). HbA1c levels did not change in the control group. |
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
–17
), syndrome X (18
) or as the "deadly quartet" (19
). Hypertriglyceridemia has been studied because these multiple risk factors all include diabetes and hypertriglyceridemia. The present study showed that long-term consumption of DG cooking oil by diabetics with hypertriglyceridemia reduces serum TG levels. Although the percentage of energy from fat in the patients in the present study was higher than the recommended levels, switching from standard cooking oil to DG cooking oil (13 g/d, equivalent to 10.4 g/d of DG) markedly reduced serum TG levels. The use of ordinary cooking oil by the control group did not affect the high serum TG levels. Thus, substituting DG cooking oil for ordinary cooking oil improved hypertriglyceridemia in patients with type II diabetes with persistent high serum TG levels despite controlled lipid and carbohydrate intakes and increased dietary fiber.
Although blood glucose levels did not decrease, HbA1c levels decreased significantly in the DG group. Previous studies (5
,6
) showed that DG ingestion had little or no effect on blood glucose levels in healthy humans. Because we have no data regarding the effect of DG ingestion on postprandial glucose levels in diabetics at present, we do not know why HbA1c levels decreased.
In the present study, the body weight in both groups did not change during the study period. In a long-term study of healthy humans (6
), DG ingestion significantly reduced intra-abdominal fat and body weight. The food energy from fat was higher in both groups in the present study compared with the previous one (6
), indicating a trend toward body fat accumulation. However, we do not know whether the increased fat content in the diet or the metabolic characteristics of the diabetics affected our results.
DG are natural components of various edible oils (7
,8
). TG in foods are hydrolyzed in the small intestine, resynthesized through 1,2-diacylglycerol (1,2-DG) into TG in the small intestinal epithelium, and released into the circulation as chylomicron-TG through the small intestinal lymphatic system. In contrast to TG, DG (mainly in the 1,3-isoform) are digested in the small intestine to 1-monoacylglycerol (1-MG) and are poorly resynthesized into TG compared with 2-MG released from TG (20
,21
). Recent studies have suggested that DG ingestion has metabolic characteristics distinct from TG (5
,6
). DG have been shown to lower the postprandial elevation of serum TG levels compared with TG (5
) in healthy humans. In addition, long-term ingestion of DG prevented the accumulation of body fat in healthy Japanese men (6
). Although the mechanisms of these effects have not been fully elucidated, the different metabolic fates of DG and TG in the small intestine due to the structural differences are more likely to be involved rather than the minor difference in fatty acid composition (5
,22
,23
).
Impaired postprandial TG clearance has been shown to be associated with visceral obesity (24
,25
). Visceral obesity is a strong predictor of type II diabetes (26
). Postprandial hyperlipidemia is also a serious issue in diabetic patients. Suppression of the extent of the postprandial serum TG increase after a single dosage of the DG emulsion compared with the TG emulsion may therefore at least partly explain the reduction of serum TG after repeated ingestion of the DG-rich oil.
Murase et al. (9
) recently reported the metabolic difference between DG and TG in C57BL/6J mice, a good model of human obesity and type II diabetes. They compared the effects of a control diet (5 g TG/100 g), a high TG diet (30 g TG + 13 g sucrose/100 g) and a high DG diet (30 g DG + 13 g sucrose/100 g) on body fat accumulation, hormone concentrations and mRNA levels of various genes involved in energy homeostasis. After 5 mo of ad libitum consumption, substituting DG oil for TG oil prevented the increases in body fat, insulin and leptin associated with a high fat and sucrose diet. Hepatic acyl-CoA oxidase activity and mRNA for acyl-CoA synthase were increased, suggesting a higher capacity for hepatic lipid oxidation. It is conceivable that there is a common mechanism underlying these results in animals and humans. Because the patients were relatively well controlled in terms of blood glucose status and we concentrated mainly on hypertriglyceridemia in the present study, the effects on insulin levels and on glucose tolerance were left as future issues for study.
Chylomicron-TG is decomposed and metabolized via the actions of peripheral tissue lipoprotein lipase (LPL). A patient with a homozygotic defect of the LPL gene suffers severe postprandial hypertriglyceridemia. We previously investigated the influence of long-term consumption of cooking oil containing >80 g DG/100 g on serum TG levels in a patient with a homozygotic defect of the LPL gene (27
). DG cooking oil significantly reduced serum TG levels in this patient. The response of the diabetic patients to dietary DG was similar to that of the patients with LPL deficiency.
The goal of nutritional counseling for diabetics is to maintain good blood sugar control and to prevent complications. Improvement in hypertriglyceridemia accompanying diabetes might relieve multiple risk factors, thus preventing arteriosclerosis. The use of DG oil might therefore be useful for maintaining the quality of life for diabetic patients. These new insights may lead to a revision of the recommended standard instructions of fat limitation by diabetics.
|
FOOTNOTES |
|---|
3 Abbreviations used: BMI, body mass index; DG, diacylglycerol; HbA1c, glycohemoglobin A1c; LPL, lipoprotein lipase; MG, monoacylglycerol; TG, triacylglycerol.
Manuscript received May 14, 2001. Revision accepted August 28, 2001.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Kissebah, A. H., Alfarsi, S., Evans, D. J. & Adams, P. W. (1982) Integrated regulation of very low density lipoprotein triglyceride and apolipoprotein-B kinetics in non-insulin-dependent diabetes mellitus. Diabetes 31:217-225.[Abstract]
2. Stern, M. P., Mitchell, B. D., Haffner, S. M. & Hazuda, H. P. (1992) Does glycemic control of type II diabetes suffice to control diabetic dyslipidemia? A community perspective. Diabetes Care 15:638-644.[Abstract]
3. Frick, M. H., Elo, O., Haapa, K., Heinonen, O. P., Heinsalmi, P., Helo, P., Huttunen, J. K., Kaitaniemi, P., Koskinen, P., Manninen, V., Mäenpää, H., Mälkönen, M., Mänttäri, M., Norola, S., Pasternack, A., Pikkarainen, J., Romo, M., Sjöblom, T. & Nikkilä, E. A. (1987) Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N. Engl. J. Med. 317:1237-1245.[Abstract]
4. Ericsson, C. G., Hamsten, A., Nilsson, J., Grip, L., Svane, B. & de Faire, U. (1996) Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet 347:849-853.[Medline]
5.
Taguchi, H., Watanabe, H., Onizawa, K., Nagao, T., Gotoh, N., Yasukawa, T., Tsushima, R., Shimasaki, H. & Itakura, H. (2000) Double-blind controlled study on the effects of dietary diacylglycerol on postprandial serum and chylomicron triacylglycerol responses in healthy humans. J. Am. Coll. Nutr. 19:789-796.
6.
Nagao, T., Watanabe, H., Goto, N., Onizawa, K., Taguchi, H., Matsuo, N., Yasukawa, T., Tsushima, R., Shimasaki, H. & Itakura, H. (2000) Dietary diacylglycerol suppresses accumulation of body fat in men; a double blind controlled trial. J. Nutr. 130:792-797.
7. Abdel-Nabey, A. A., Shehata, A.A.Y., Ragab, M. H. & Rossell, J. B. (1992) Glycerides of cottonseed oils from Egyptian and other varieties. Riv. Ital. Sostanze Grasse 69:443-447.
8. D’alonzo, R. P., Kozarek, W. J. & Wade, R. L. (1982) Glyceride composition of processed fats and oils as determined by glass capillary gas chromatography. J. Am. Oil Chem. Soc. 59:292-295.
9.
Murase, T., Mizuno, T., Omachi, T., Onizawa, K., Komine, Y., Kondo, H., Hase, T. & Tokimitsu, I. (2001) Dietary diacylglycerol suppresses high fat and high sucrose diet-induced fat accumulation in C57BL/6J mice. J Lipid Res 42:372-378.
10. The Ministry of Science and Technology (1998) 4th Revision of the Standard Tables of Food Composition in Japan 1998.
11.
Ellis, G., Diamandis, E. P., Giesbrecht, E. E., Daneman, D. & Allen, L. C. (1984) An automated "high-pressure" liquid-chromatographic assay for hemoglobin A1c. Clin. Chem. 30:1746-1752.
12. The Ministry of Public Health and Welfare (2000) Japanese National Nutrition Survey in 1998 2000 Dai-ichi Shuppan Publishing Co. Ltd. Tokyo, Japan .
13. The Ministry of Health and Welfare (1999) In: Recommended Daily Allowances of Nutrition for the Japanese People 6th rev. 1999 Dai-ichi Shuppan Publishing Co. Ltd Tokyo, Japan. .
14. Shima, K., Endo, J., Oimoni, M., Oshima, I., Omori, Y., Katayama, Y., Kanazawa, Y., Kawai, T., Kawamori, R., Kanno, T., Kiyose, H., Nakashima, K., Nagamine, Y., Baba, S., Hoshino, T. & Amino, N. (1994) Interlaboratory difference in HbA1c measurement in Japan—A report of the committee of an Interlaboratory Standardization of HbA1c Determination, the Japan Diabetes Society. J. Japan Diab. Soc. 37:855-864.
15. Fujioka, S., Matsuzawa, Y., Tokunaga, K. & Tarui, S. (1987) Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism 36:54-59.[Medline]
16. Nakamura, T., Tokunaga, K., Shimomura, I., Nisida, M., Yoshida, S., Kotani, K., Islam, A.H.M.W., Keno, Y., Kobatake, T., Nagai, Y., Fujioka, S., Tarui, S. & Matsuzawa, Y. (1994) Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men. Atherosclerosis 107:239-246.[Medline]
17. Tokunaga, K. (1998) Visceral obesity and atherosclerosis. J. Jpn. Soc. Stud. Obes. 4:5-9.
18. Reaven, G. M. (1988) Role of insulin resistance in human disease. Diabetes 37:1595-1607.[Abstract]
19. Kaplan, N. M. (1989) The deadly quartet. Arch. Intern. Med. 149:1514-1520.[Abstract]
20. Bierbach, H. (1983) Triacylglycerol biosynthesis in human small intestinal mucosa 1983 Acyl-CoA monoglyceride acyltransferase. Digestion 28 138–147. .
21. Watanabe, H., Onizawa, K., Taguchi, H., Kobori, M., Chiba, H., Naito, S., Matsuo, N., Yasukawa, T., Hattori, M. & Shimasaki, H. (1997) Nutritional characterization of diacylglycerols in rats. J. Jpn. Oil Chem. Soc. 46:301-307.
22. Hara, K., Onizawa, K., Honda, H., Otsuji, K., Ide, T. & Murata, M. (1993) Dietary diacylglycerol-dependent reduction in serum triacylglycerol concentration in rats. Ann. Nutr. Metab. 37:185-191.[Medline]
23. Murata, M., Hara, K. & Ide, T. (1994) Alteration by diacylglycerols of the transport and fatty acid composition of lymph chylomicrons in rats. Biosci. Biotechnol. Biochem. 58:1416-1419.
24. Couillard, C., Bergeron, N., Prud’homme, D., Bergeron, J., Tremblay, A., Bouchard, C., Mauriege, P. & Despres, J. P. (1998) Postprandial triglyceride response in visceral obesity in men. Diabetes 47:953-960.[Abstract]
25.
Mekki, N, Christofilis, M. A., Charbonnier, M., Atlan-Gepner, C., Juhel, C., Borel, P., Portugal, H., Pauli, A. M., Vialettes, B. & Lairon, D. (1999) Influence of obesity and body fat distribution on postprandial lipemia and triglyceride-rich lipoproteins in adult women. J. Clin. Endocrinol. Metab. 84:184-191.
26.
Bjorntorp, P. & Rosmond, R. (1999) Hypothalamic origin of the metabolic syndrome X. Ann. N.Y. Acad. Sci. 892:297-307.
27. Yamamoto, K., Yagi, N., Asakawa, H. & Tokunaga, K. (2000) Effect of the long-term consumption of dietary diacylglycerol on the serum triglyceride of a patient with a homozygotic defect of the lipoprotein lipase gene. J. Jpn. Atheroscler. Soc. 28:117(abs.).
This article has been cited by other articles:
|
|
 |
|
  G. Reyes, K. Yasunaga, E. Rothenstein, W. Karmally, R. Ramakrishnan, S. Holleran, and H. N. Ginsberg Effects of a 1,3-diacylglycerol oil-enriched diet on postprandial lipemia in people with insulin resistance J. Lipid Res., March 1, 2008; 49(3): 670 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamamoto, K. Tomonobu, H. Asakawa, K. Tokunaga, T. Hase, I. Tokimitsu, and N. Yagi Diet Therapy With Diacylglycerol Oil Delays the Progression of Renal Failure in Type 2 Diabetic Patients With Nephropathy Diabetes Care, February 1, 2006; 29(2): 417 - 419. [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Kamphuis, D. J Mela, and M. S Westerterp-Plantenga Diacylglycerols affect substrate oxidation and appetite in humans Am. J. Clinical Nutrition, May 1, 2003; 77(5): 1133 - 1139. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
