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Volume 5, Number 4, Section 2

The 5th International Symposium on Clinical Nutrition (4-7 Feb 1996)

VII. Diagnosis and management of dyslipidaemia

40. Impact of insulin resistance on dyslipidaemia

Khalid BAK

Insulin deficiency due to resistance inhibits LPL activity. Thus, there is both increased production and decreased clearance. The picture is obscured because hypertriglyceridaemia may cause insulin resistance. The hyperinsulinaemia seen in diabetes may also not be due to insulin but to proinsulins and insulin fragments

Insulin resistance is one of the mechanisms of pathogenesis of non-insulin dependent diabetes. This is associated with hyperinsulinaemia, hyperuricaemia and hypertension. The lipid abnormalities seen in NIDDM are hypertriglyceridaemia with increased very low density lipoprotein, remnant particles and reduced high density lipoproteins. Diabetes is also associated with increased total cholesterol and low density lipoprotein cholesterol. Insulin resistance in NIDDM results in both relative deficiency of insulin action and hyperinsulinaemia. Insulin promotes triglyceride and cholesterol synthesis and inhibits lipolysis in adipose tissues, partly by stimulating lipoprotein lipase.


41. Dietary intervention in dyslipidaemia

Tanphaichitr V, Pakpeankitvatana R, Leelahagul P

Appropriate dietary intake plays an important role in regulating serum lipoprotein levels. High intakes of total energy, saturated fatty acids (SFAs), and dietary cholesterol can raise serum total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) levels. Four principles have been recommended to lower serum TC and LDL-C levels for the general population and high risk individuals, ie, to control obesity by decreasing energy intake and increasing physical activity, to reduce total fat intake to 30% of total calories with equal distribution of SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, to reduce daily cholesterol intake to <300mg, and to have protein and carbohydrate intakes of 10-20 and 50-60% of total calories, respectively. Our studies have shown that total fat and linoleate (18:2n-6) intakes of 30 and 10% of total calories can lower serum TC and LDL-C levels but this effect depends on the amount of cholesterol intake. The prevailing evidence suggests that the decrease in serum LDL-C level induced by 18:2n-6 is a result of modified secretion of cholesteryl ester and increased LDL receptor function. Consumption of fish oil rich in eicosapentaenoic (20:5n-3) and docosahexenoic (22:6n-3) acids has been almost uniformly shown to lower serum triglyceride (TG) levels both in normal subjects and hypertriglyceridaemic patients with dose-dependent response. The plausible TG-lowering effects of fish oil include reducing TG synthesis and chylomicron secretion from intestinal cells, limiting VLDL secretion by suppressing hepatic fatty acid synthesis and TG production, and reducing apoprotein B synthesis and lipoprotein release. Moderate consumption of sugars and restricted intake of alcohol should be implemented in hypertriglyceridaemic patients.


42. Dietary management of hyperlipidaemia - a survey in Malaysian hospitals

Karupaiah T, Chee SS

Coronary Heart Disease (CHD) is recognised as an important public health problem in Malaysia. Hyperlipidaemia is one of the main risk factors related to CHD. The mainstay of treatment is diet therapy which should be maintained even if drug treatment is indicated. In the absence of any national guidelines in Malaysia for dietary management of hyper-lipidaemia, diet therapy has remained individualistic. Since dietitians are the primary providers of dietary treatment to hyperlipidaemic patients. this retrospective study attempts to report the dietary approaches and methodologies adopted by Malaysian dietitians in managing their patients. A postal questionnaire covering various aspects of dietary management of hyperlipidaemia were sent to all dietitians practising in private and government hospitals. Of interest to this study were dietary assessment techniques, dietary recommendations, dietary compliance, together with objective measures such as changes in body weight and blood parameters. The study is in progress and results will be presented at the 5th Clinical Symposium in Bangkok.


43. Pharmacological intervention and LDL-aphaeresis of familial hypercholesterolaemia

Hiroshi Mabuchi

Familial hypercholesterolaemia (FH) is a disease characterised by severe hypercholesterolaemia and premature coronary heart disease (CHD). One hundred patients of our 1,400 FH heterozygotes died; 68 patients (68%) died of CHD. Since the lower the plasma cholesterol level, the more likely it is that CHD can be prevented or retarded, aggressive cholesterol-lowering therapies may be indicated for FH patients with CHD. This study describes the long-term safety and efficacy of intensive cholesterol lowering therapies with drugs as well as LDL-aphaeresis for the management of heterozygous FH patients. One hundred and eighty-four (137 male, 47 female) heterozygous FH patients with CHD documented by coronary angiography had been treated by cholesterol-lowering drug therapy alone or in combination with coronary artery bypass grafting (CABG) surgery, percutaneous transluminal coronary angioplasty (PTCA) or low density lipoprotein (LDL)-aphaeresis. Serum lipid levels and outcomes in each treatment group were compared after 6.5 years. LDL-aphaeresis significantly reduced serum cholesterol and LDL-cholesterol levels as compared to the groups receiving other therapies. Four patients (10%) of 39 patients treated by CABG, one (3%) of 35 patients treated by LDL-aphaeresis, one (4%) of 25 patients treated by PICA, 6 (10%) of 59 patients treated by drugs, and 7 (27%) of 26 patients receiving no cholesterol-lowering therapy died of CHD. The patients treated by LDL-aphaeresis (p<0.01) and drugs (p<0.05) had a better prognosis than those receiving no cholesterol-lowering therapy. Thus, for the treatment of CHD in FH heterozygotes, intensive LDL-cholesterol-lowering therapies are effective, and LDL-aphaeresis may become the therapy of choice.


44. Protein-energy status in athletic swimmers

Chatchatree N, Leelahagul P, Tanphaichitr V

Protein-energy status was assessed in 13 athletic swimmers, consisting of 10 boys and 3 girls with the age ranging from 10 to 16 yrs, by anthropometric parameters and serum transport protein levels. Their height-for-age and weight-for-age were compared with those of international reference population derived from US National Center for Health Statistics.

All of them had height-for-age within median±2SD whereas 11 had weight-for-age within median±2SD and only 1 had weight-for-age above median±2SD. These findings indicate that only 1 subject was obese. His height was 1.62m and body weight was 73.8kg constituting of 24.8kg body fat mass. The means±SEM of their serum albumin, transferrin, and retinol-binding-protein levels were 45.14±0.35g/L, 3.02±0.09g/L, and 44.91±1.55mg/L, respectively. All of the individual values were also within the acceptable levels. The results indicate that these athletic swimmers had adequate visceral protein status.


45. Carnitine status in athletic swimmers

Suwan K, Leelahagul P, Tanphaichitr V

Plasma and urinary carnitine levels were determined in 13 athletic swimmers consisting of 10 males and 3 females with the mean (±SEM) age of 13.2±0.5 yrs. Means ±SEM of free, acyl, and total carnitine levels in plasma and urine are shown below. Plasma total carnitine consisted of 47.2% of free carnitine and 52.8% of acyl carnitine whereas the corresponding figures for urinary carnitine were 42.1% and 57.9%. There were no significant relationships between the corresponding forms of carnitine in plasma and urine. Based on urinary total carnitine excretions of < 150, 150-500, and > 500 mol/day to indicate carnitine deficiency, adequate carnitine status, and increased catabolism, respectively, 8 swimmers (61.5%) had adequate carnitine status whereas 5 swimmers (38.5%) were in catabolic state. We also observed significant positive correlations between urinary acyl carnitine and fat-free mass (r = 0.5639, p < 0.05); urinary acyl carnitine and urinary creatinine excretion (r=0.6769, p < 0.0001 ), as well as between urinary total carnitine and urinary creatinine excretion (r = 0.4970, p < 0.01 ). These findings are consistent with the fact that most of body carnitine resides in skeletal muscle.

 

Carnitine

Sample

Free

Acyl

Total

Plasma (mol/L)

51.54 ± 1.75

57.77 ± 3.13

109.31 ± 3.81

Urine (mol/d)

174.53 ± 23.21

240.22 ± 18.77

414.74 ± 39.85


46. Effects of dietary changes on serum lipoprotein levels in us peace corps volunteers working in Thailand

Putadechakum S, Stolberg C, Leelahagul P, Tanphaichitr V

Effects of dietary changes on serum lipoprotein levels were investigated in 20 US Peace Corps Volunteers (PCV) consisting of 4 men and 16 women with the age ranging from 21-35 years. Dietary, anthropometric, and biochemical assessments were performed within 3 days after their arrival (wk0) and during working in Thailand at wks 12 and 36. Though their mean serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) levels were within the desirable levels their mean serum TC and LDL-C levels at wks 12 and 36 were significantly higher than those at wk 0 (p<0.05). These changes could be due to (a) the increase in lipolysis of adipose tissue which may raise the supply of free fatty acids to the liver; this event may lead to the increased hepatic cholesterol content which down regulates the activity of hepatic LDL-receptors with the final development of increased serum LDL-C levels; this mechanism is supported by the decreases in their daily intakes of total energy, total fat, saturated fatty acids, and cholesterol at wks 12 and 36 with concomitant decrease in their body fat, and/or (b) significant decreases in their dietary fibre intakes at wks 12 and 36 which may increase cholesterol absorption evidenced by significantly negative correlations between dietary fibre intakes and serum TC levels (r=-0.4651, p=0.004) as well as between dietary fibre intakes and serum LDL-C levels (r= -0.3616, p=0.028).

Lipoprotein Wk 0 Wk 12 Wk 36
  mmol/L mmol/L mmol/L
TC 4.050.17 4.720.15* 4.640.1
LDL-C 2.280.18 2.870.14* 2.850.12*
HDL-C 1.330.07 1.250.06 1.230.07
TG 1.310.10 1.110.06 1.220.12

47. Serum lipids status of rats as affected by fed different fatty acid composition oils

Ling Chengde, Li Juhua, Hua Jingzhong, Chen Zhonli

The serum lipids of rats fed different fatty acid composition oils were investigated. 40 adult female SD rats were randomly divided into four groups, all rats were exposed on a high lipidic diet and each rat of group A and B were given 1.0 and 0.5ml/d test oil, respectively, which consisted of various plant oils. Group C was given refined rape seed oil, and group D was a control. The experimental duration was 40 days. The results showed that the levels of serum total cholesterol (TC) and triglyceride (TG) in the rats of group A, B and C were lower than that of the control (P < 0.05). No significant difference of the high density lipoprotein cholesterol (HDL-C) in the serum was observed among each group. The ratio of TC to HDL-C in group A, B, and C were significantly lower than the control (P<0.05 or P<0.01). The difference of the serum lipid levels among the test groups was not significant.

It could be concluded that the various plant oils including rape seed oil have significant effects on reducing serum TC and TG, but these oils did not affect the HDL-C level in the test rats.


48. Potential benefits of tempeh for lowering cholesterol: implications for future studies

Hardinsyah, Wahlqvist ML and Marks GC

Tempeh is a non-salted fermented soybean food which was originally developed in Indonesia, where hypercholesterolaemia is now considered to be one of the health problems, especially among adult urban residents. Previous studies on the benefits of tempeh have focused on the nutrients, its contribution to infant formula, and on anti-bacterial components in diarrhoeal therapy. There is growing interest in the benefit of soybean products in coronary heart diseases prevention. This paper reviews potential benefits of tempeh in lowering cholesterol.

Studies on the health benefits of non-fermented soy products (NFS) suggest that NFS have a hypocholesterolaemic effect (HE) in humans. However, no studies assessed the HE of tempeh in humans. Limited animal studies have confirmed that tempeh has a HE in rats. Cholesterol lowering components, such as unsaturated fatty acids, soy protein and antioxidants (b-carotene + isoflavones), in NFS are also present in tempeh. Fermentation increases availability of oleic acid, and the bioavailability of protein and zinc in tempeh. The content of isoflavones, particularly genistein and daidzein, in tempeh is higher than in NFS (193 and 137g/g in tempeh vs 52 and 46g/g in soymilk); and 6,7,4-trihydroxy isoflavone (factor-2) have only been identified in tempeh. These data suggest that tempeh may also have a HE in humans, and this may be greater than for NFS.

If the HE of tempeh is confirmed in humans, further studies are required to investigate the mechanisms by the suspected components, the application of tempeh and tempeh products as a practical dietary approach, and appropriate promotion strategies for these products as part of healthy diet. Finally, studies would be needed to develop medical products from tempeh, as alternatives for those who would not accept tempeh. Such studies could make an important contribution to health status in Indonesia, where tempeh is consumed by over 45% of the population, as well as in developed countries, where tempeh and tempeh products are becoming more popular.


49. The effect of tempeh (soybean cake) and tempeh formula on lipid profile of hyperlipidaemic patients

Arsiniati M Brata-Arbai, Askandar Tjokroprawiro

In this study 75 men age 40-65 years with total cholesterol (T-chol) > 220 mg/dL and triglyceride > 175 mg/dL were divided in three groups. The first group were treated for two weeks with Standard Diet (DS), the second group were given Standard Diet plus 150 gram tempeh (soybean cake) (DS+T) and the third group were given Standard Diet plus 67.50 tempeh-A5 (DS+T-A5) tempeh formula of tempeh, which contained tempeh powder, lecithin, fibre, aspartame and mixed vegetable oil.

Result: DS: T-chol decreased 4.36% (ns); triglyceride 7.59% (s); LDL-chol 4.43X (ns); HDL-chol increased 5.51% (ns); Ratio T-chol / HDL-chol decreased 7.18% (ns).

DS+T: T-chol decreased 8.38% (s); triglyceride = 9.19% (ns); LDL-chol decreased 8.29% (s); HDL-chol increased 8.47% (ns). Ratio T-chol/ HDL-chol decreased 13.38% (s).

DS+T-A5: T-chol decreased 18.59% (s); triglyceride 13.76% (ns); LDL-chol 16.76% (s); HDL-chol increased = 24.19% (s); decreased in Ratio T-chol/HDL-chol = 35.48% (s) p<0.05.

Conclusion: Tempe and Tempe-A5 possess hypolipidaemic effect significantly by lowering T-chol and LDL-chol. Tempe-A5 also increased HDL-chol and has stronger hypolipidaemic effect than tempeh.


50. Variability of fat load response by aging and genetic factors

Terada S, Kajiki Y, Ikemoto S, Matsumoto A, Kondo K, Itakura H

Postprandial hyperlipidaemia is reported to be associated with an increased risk of atherosclerosis. There is considerable individual variability in the postprandial lipid response to a meal. To evaluate the factors which may account for the difference we studied the effects of aging and DNA polymorphism on postprandial lipid response to a fat load. Twenty-six young and seventeen older healthy female subjects were given a fat load consistent of 30g/m2 body surface of milk fat. Blood was drawn at time 0 and every hour during a 6 hour period. We examined the relation between the gene polymorphism and postprandial levers of serum triglyceride. Fasting serum triglyceride levels were higher in older women, but there was no difference in postprandial responses of serum triglyceride between the two age groups.

We detected some difference of postprandial response in DNA polymorphism. Such as D/I polymorphism of signal peptide of apo B, apo E variant (E2, E3, E4) and D/I polymorphism of ACE gene. Elevations of serum triglyceride after fat load were observed in ID type of apo B gene, E2 variant of apo E gene and DD type of ACE gene.

In conclusion, analysis of DNA polymorphism is useful for the evaluation of genetic factors of postprandial response.


51. Lipoproteins and lipid peroxidation abnormalities in patients with chronic renal disease

Ong-ajyooth S, Ong-ajyooth L, Sirisalee K, Nilwarangkur S

Increasing experimental and clinical evidence suggests that lipoproteins and lipid peroxidation can be important modulators in progressive kidney disease. A group of 54 patients with varying degree of kidney impairment was studied to find the abnormalities in lipoproteins and lipid peroxidation. Lipoproteins and lipid peroxidation products, malonaldehyde (MDA) were measured in the plasma of 54 chronic renal disease patients (CGN 33, nephrosclerosis 11, 7 CTIN, 1 PCKD, unknown 2) and compared with values obtained from 32 healthy controls. The patients were divided into 5 groups according to serum creatinine levels. All groups had significantly elevated plasma MDA VS controls (p<0.0001). Serum lipoproteins also correlate with plasma MDA (r=0.52). Results: Mean ± SD; *p<0.05, **p<0.0001 vs normal.

Patients with chronic renal disease showed lipoprotein abnormalities and accelerated lipid peroxidation. The evidence was more marked in patients with normal to mild renal insufficiency which suggested the role of oxidative stress early in the course of nephron injury.

  Normal Group 1 Group 2 Group 3 Group 4 Group 5
Scr (mg/dL) 0-1.5 <2 2-4 >4-8 >8-12 >12
Pe chol (mg/dL) 208 ± 32 273 ± 127* 358 ± 137** 242 ± 90 234 ± 65 218 ± 52
LDL-chol 132 ± 36.2 181 ± 110* 273 ± 162** 153 ± 92 154 ± 55 141 ± 35
VLDL-chol 18 ± 8.6 39 ± 15.7** 75.9 ± 52** 37 ± 20.7* 30 ± 10.9* 37.9 ± 15*
HDL-chol 52.6 ± 9.2 47.7 ± 28 40 ± 16.8* 39 ± 9* 39 ± 9.5* 27 ± 10.6**
Pl trig (mg/dL) 95.3 ± 42 199 ± 78.8** 423 ± 766** 214 ± 124** 149 ± 56* 181 ± 63.4**
Pl MDA (mol/L) 7 ± 3.1 120 ± 45.7** 165 ± 95.8** 75 ± 76.6** 72 ± 37** 74 ± 43**

52. Influence of overall obesity and abdominal obesity on health risk in obese women

Mesomya W, Leelahagul P, Pakpeankitvatana R, Tanphaichitr V

The influence of overall obesity based on body mass index (BMI) of 25.0kg/m2 and abdominal obesity based on waist-over-hip circumference ratio (WHR) of >0.8 on blood pressure (BP), serum lipoproteins, plasma fibrinogen, and blood glucose levels were evaluated in 22 obese women . Throughout the 16-wk study, they were instructed to decrease their energy intake with dietary energy distribution of 20% protein, 30% fat, and 50% carbohydrate calories. The subjects took 4g of sweet basil seed extract (SBSE) daily during wks 4-16. BMI, WHR, BP, serum lipoproteins, plasma fibrinogen, and blood glucose were measured at 4-wk intervals in all of them during the study. Prior to the SBSE treatment, all of the women had BMI of >25.0 kg/m2 and WHR of >0.8. Out of 22 obese women, 11 (50%) showed a decrease in their body weight > 2 times during wks 8-16 from that at wk4. Linear regression analysis revealed that their BMI had significantly positive correlations with their systolic BP (r=0.4043, p<0.00001), diastolic BP (r=0.4163, p<0.00001), serum M-particle levels (r=0.2772, p=0.0034) and plasma fibrinogen levels (r=0.2664, p=0.0055), whereas their WHR showed significant positive correlations with their systolic BP (r=0.5583, p<0.00001), diastolic BP (r=0.4476, p<0.00001), serum total cholesterol (r=0.3480, p=0.0002), triglyceride (r=0.4318, p<0.00001), apo-B (r=0.3153, p=0.0008), M-particle (r=0.4142, p<0.00001), S-particle (r=0.2476, p=0.0094), plasma fibrinogen (r=0.3736, p=0.0001), and blood glucose (r=0.3387, p<0.0058) levels. The results imply that abdominal obesity coexisting with overall obesity aggravates adverse effects on BP, serum lipoprotein, plasma fibrinogen and blood glucose levels.


53. Plasma lipoprotein levels in athletic swimmers

Thongmung N, Pakpenkitvatana R, Tanphaichitr V

Plasma lipid levels were determined in 13 athletic swimmers consisting of 10 males and 3 females with the mean (±SEM) age of 13.2±5 yrs. Their means (±SEM) of serum total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) levels were 5.61±0.17, 3.51±0.15, 1.71±0.07, and 0.85±0.06 mmol/L, respectively. Plasma lipoprotein analysis was performed by sequential ultracentrifugation technique followed by enzymatic determination of lipid in each lipoprotein fraction. The cholesterol contents in VLDL, LDL, and HDL were 0.82±0.07 (18.5%), 3.10±0.14 (57.0%), and 1.39±0.05 (24.5%) mmol/L, respectively, whereas the TG contents in these 3 lipoproteins were 0.28±0.03 (40.3%), 0.22±0.02 (30.7%), and 0.20±0.03 (29.0%) mmol/L. None of the swimmers had serum HDL-C levels <0.90mmol/L, 10 (76.9%) had serum HDL-C levels of 1.55mmol/L, and all of them had serum TG levels of < 2.26mmol/L. These findings are consistent with their high physical activity. However, 8 swimmers (61.5%) had serum LDL-C levels of 3.36-4.12mmol/L and 5 (39.5%) had serum LDL-C levels < 3.36mmol/L. There were no significant differences in their energy distribution or cholesterol intake in these 2 groups. It should be noted that the mean (±SEM) energy distribution and cholesterol intakes in these 13 swimmers were 15.9% protein, 49.1% fat, 35.0% carbohydrate, and 668mg/d, respectively.

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Revised: January 19, 1999 .