Abdominal defects

After a fatty meal, intestinal (chylomicrons and chylomicroii remnants containing apolipoprotein) and liver-derived triglyceride rich lipoproteins contribute to postprandial increase in lipids. Along with fasting hyperlipidaemia, excess postprandial lipid levels (postprandial hyperlipidaemia; PPHL), independent of other cardiovascular risk factors, have been implicated in the pathogenesis of atherosclerosis and considered to be a component of insulin resistance syndrome (metabolic syndrome). Greater than 80 per cent increase in postprandial triglycerides over the fasting value has been suggested as cut-off point for significant postprandial hypertriglyceridaemia based on its significant association with insulin resistance1.

Postprandial state affects the physical characteristics and composition of lipoprotein particles, principally mediated by the effects of cholestryl ester transfer protein (CETP) and hepatic lipase. CETP catalyses the transfer of cholestryl esters from high density lipoprotein (HDL) and low density lipoprotein (LDL) to chylomicrons, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL), and reciprocal transfer of triglycerides. The conversion of triglyceride-enriched LDL particle into small dense LDL by the action of hepatic lipase additionally influences the magnitude and duration of PPHL.While fasting hypertriglyceridaemia is closely associated with PPHL, some data suggest that each is associated with different set of determinants2. For example, dietary imbalance and alcohol intake appear to be more important determinants of PPHL than fasting hypertriglyceridaemia. Importantly, depending upon the timing and duration of meals, postprandial hyperlipidaemic state may persist for 15 to 18 h, making it potentially more atherogenic than fasting hyperlipidaemia alone.

Recent research shows close association of PPHL with atherosclerosis. PPHL is closely correlated with carotid intima-media thickness in normolipidaemicand hyperlipidaemic individuals independent of other risk factors2"4. Higher daytime triglyceridaemia with similar fasting triglyceride levels was observed in subjects with premature coronary artery disease (CAD) as compared to their first-degree relatives without CAD5. Indeed some evidence suggests that postprandial plasma triglyceride levels (3-4 h postmeal) predict future myocardial infarction better than fasting triglyceride levels6.

How does PPHL induce atherosclerosis? It is associated with alterations in several atherogenic factors; increase in intestinally-derived chylomicrons and their remnants, increase in VLDL and remnants secreted by liver, decrease in HDL, and increase in small dense LDL particles which are more susceptible to oxidation. In addition, it is associated with increased activity of factor VII (a procoagulant effect), and increase in the level of plasminogen activator inhibitor-1 (an anti-fibrinolytic effect). The effects of PPHL on sub-clinical inflammation and adiponectin, important for atherogenesis and insulin resistance respectively, remain to be investigated. Accumulation of chylomicron remnants (apo B48 and apo B100-containing particles) with prolonged PPHL results in their migration through the vessel wall into the subendothelial space and initiation of atherosclerosis7. Further, triglyceride-rich lipoproteins hydrolyzed by lipoprotein lipase raise levels of fatty acid anions in the vicinity of endothelium, disrupting its integrity and causing dysfunction, and also potentiate tumour necrosis factor- mediated endothelial injury. Another mechanism for accelerated atherosclerosis in subjects with postprandial hypertriglyceridaemia is increase in circulating adhesion molecules8.

Research in PPHL is a particularly important issue for ethnic groups with high tendency to develop metabolic syndrome, dyslipidaemia and CAD, such as Asian Indians and Hispanics. Dyslipidaemia in Asian Indians is usually characterized by hypertriglyceridaemia, low levels of HDL, and high levels of small dense LDL (a cluster of abnormalities termed as atherogenic dyslipidaemia) which frequently occurs in conjunction with PPHL9"12. Excess abdominal adiposity; commonly observed in Asian Indians13-15, may be another important factor that may cause PPHL16, and is associated with increased levels of postprandial insulin and free fatty acids. Not only the prevalence of abdominal obesity is high in Asian Indians, but the total mass of subcutaneous and intra-abdominal fat is higher than white Caucasians13,15,17-21. In white Caucasians, "hypertriglyceridaemic waist" phenotype (individuals having fasting hypertriglyceridaemia and high waist circumference) is associated with significantly greater postprandial triglycerides and CAD22. It appears that subjects with excess visceral adipose tissue may have decreased post-heparin plasma lipoprotein Iipase activity due to either defects in insulin secretion or insulin resistance, thus impairing clearance of triglycerides during postprandial state16.

PPHL after high fat meal is well documented. High carbohydrate content (>55% energy) in diets also causes hypertriglyceridaemia, despite low fat content. Beneficial effects of very low-carbohydrate diet in improving PPHL and other components of metabolic syndrome have been reported23. In Asian Indians, postprandial hypertriglyceridaemia in treated patients with type 2 diabetes was principally seen in those consuming high carbohydrate and low fat diets24. However, comparative dietary studies with other ethnic groups have not been done, and different carbohydrate containing dietary articles have not been tested. Both these important issues have been dealt in the study of Ezenwaka and Kalloo25 on healthy and diabetic East Indian (ethnic population with ancestral origin from Indian subcontinent) and African subjects, published in the current issue of the journal. Interestingly, these investigators showed that subjects had highest tendency to develop hypertriglyceridaemia with brown bread meal followed by diets containing rolls and rice. Moreover, these effects were particularly seen in East Indian diabetic patients. These findings dispel a popular notion in South Asians that brown bread is better than other two dietary articles, and that rotis are better than rice, for maintaining healthy metabolism in non-diabetic individuals, and is beneficial for diabetic patients. Importantly, rotis and rice are frequently consumed by South Asians originating not only from India, but also by populations living in Pakistan, Bangladesh, Sri Lanka, Nepal, Mauritius, and many countries in Middle East. Brown bread, on the other hand, is available in India only in major cities and mostly consumed by persons belonging to urban middle- or high-income groups. The persons living in rural areas either consume rotis or rice as staple dietary items.

Although novel, the observations of Ezenwaka and Kalloo25 are based on a short-term diet study of seven days and should be deemed as preliminary. A closer look at the dietary composition also reveals subtle difference in the total carbohydrate and fat contents of the diets, both being higher in the diet containing brown bread due to addition of cheese. The investigators should have considered several body composition variables while analyzing PPHL data. For example, the magnitude of PPHL depends on the BMI of the individuals; high carbohydrate diets (76% energy) with markedly low fat content (8% energy) resulted in 30 per cent increase in the postprandial triglycerides in CAD patients with BMI > 28 kg/m^sup 2^, while there was no change in those with BMI

Individual or population difference of postprandial hypertriglyceridaemia in response to diet may be due to genetic, hormonal and/or environmental factors. Among genetic factors apolipoprotein E genotype has been most frequently studied. In Japanese men apo E phenotype E3/4 was associated with an impaired postprandial triglyceride-rich Hpoprotein metabolism relative to apo E3/3 phenotype when matched for intra-abdominal viscera! fat accumulation27. In nonobese Korean men, the presence of the C allele in the APOA5 promoter region at position 1131 significantly contributed to PPHL28. A study on limited number of subjects suggests that postprandial lipaemic response is modified by polymorphism at codon 54 of fatty acid-binding protein 2 gene29. Similarly, peroxisome proliferators-activated receptor- may impact postprandial handling of lipoproteins30. These data suggest that gene-diet interactions are important for handling of lipoproteins in the postprandial period. Studies along these lines in Asian Indians might be useful.

Despite the growing literature on PPHL, several issues remain unanswered. First, the precise cut-off point for PPHL is not yet known. second, how important is PPHL in the causation of CAD in Asian Indians? Heterogeneous etiological factors for CAD preclude simple answers to this question. PPHL should be viewed as an important cardiovascular risk factor in the realm of abdominal obesity and metabolic syndrome in Asian Indians. Whether it contributes independently to the risk of CAD in Asian Indians remains to be investigated. Third, should PPHL be investigated routinely? No guidelines are available on this issue. One could presume that PPHL is present in patients with fasting hypertriglyceridaemia. It would be rational to investigate for PPHL in those with normal fasting lipid levels but having abdominal obesity. Fourth, what are the treatment options for PPHL in Asian Indians? Diet and physical exercise should be advised to reduce abdominal obesity and insulin resistance. An important issue would be how low should be a low carbohydrate diet to effectively prevent PPHL? Further studies should also clarify which carbohydrate diets that have fewer propensities to cause PPHL should be avoided. The observations of Ezenwaka and Kalloo25 should be critically tested in further trials. Diet-gene interactions of PPHL should be investigated although practical implications are limited. Several drugs could improve postprandial lipoprotein metabolism, including -3 fatty acids, (HMG Co-A) reductase inhibitors, and thiazolidinediones, however, usefulness of these drugs in those with PPHL alone remains to be investigated. Finally, whether reduction of PPHL leads to reduction of cardiac- and all-cause mortality in all ethnic groups including Asian Indians is yet an unresolved issue.

References

1. Karamanos BG, Thanopoulou AC, Roussi-Penesi DP. Maximal post-prandial triglyceride increase reflects post-prandial hypertriglyceridaemia and is associated with the insulin resistance syndrome. Diabet Med 2001 ; 18 : 32-9.

2. Sharrett AR, Chambless LE, Heiss G, Paton CC, Patsch-W. Association of postprandial triglyceride and retinyl palmitate responses with asymptomatic carotid artery atherosclerosis in middle-aged men and women. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vase Biol 1995; 15:2122-9.

3. Ryu JE, Howard G, Craven TE, Bond MG, Hagaman AP, Grouse JR, 3rd. Postprandial triglyceridemia and carotid atherosclerosis in middle-aged subjects. Stroke 1992; 23 : 823-8.

4. Karpe F, de Faire U, Mercuri M, Bond MG, Hellenius ML, Hamsten A. Magnitude of alimentary'lipemia is related to intima-media thickness of the common carotid artery in middle-aged men. Atherosclerosis 1998; 141 : 307-14.

5. Geluk CA, Halkes CJ, De Jaegere PP, Plokker TW, Cabezas MC. Daytime triglyceridemia in normocholesterolemic patients with premature atherosclerosis and in their first-degree relatives. Metabolism 2004; 53: 49-53.

6. Stampfcr MJ, Krauss RM, Ma J, Blanche PJ, HoII LG, Sacks FM, et al. A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 1996; 276 : 882-8.

7. Proctor SD, Mamo JC. Retention of fluorescent-labelled chylomicron remnants within the intima of the arterial wall-evidence that plaque cholesterol may be derived from post-prandial lipoproteins. Eur J Clin Invest 1998; 28 : 497-503.

8. Ceriello A, Quagliaro L, Piconi L, Assaloni R, Da Ros R, Maier A, et al. Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes 2004; 53 : 701-10.

9. Misra A, Luthra K, Vikram NK. Dyslipidemia in Asian Indians: Determinants and significance. J Assoc Physicians India 2004; 52 : 137-42.

10. Misra A, Cluuidhary D, Vikram NK, Mittal V, Devi JR, Pandey RM, el al. Insulin resistance and clustering of atherogenic risk factors in women belonging to low socio-economic strata in urban slums of North India. Diabetes Res Clin Pract 2002; 56: 73-5.

11. Misra A, Pandey RM, Devi JR, Sharma R, Vikram NK, Khanna N. High prevalence of diabetes, obesity and dyslipidaemia in urban slum population in northern India. InI J Obes ReIaI Metab Disord 2001; 25 : 1722-9.

12. Misra A, Reddy RB, Reddy KS, Mohan A, Bajaj JS. Clustering of impaired glucose tolerance, hyperinsulinemia and dyslipidemia in young north Indian patients with coronary heart disease: a preliminary case-control study. Indian Heart J 1999; 51 : 275-80.

13. Misra A, Vikram NK. Insulin resistance syndrome (metabolic syndrome) and Asian Indians. Curr Sd 2002; 83 : 1483-96.

14. Misra A. Body composition and the metabolic syndrome in Asian Indians: a saga of multiple adversities. Nail Med J India 2003; 16:3-7.

15. Misra A, Vikram NK. Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots. Nutrition 2003; 19 : 457-66.

16. Couillard C, Bergeron N, Prud'homme D, Bergeron J, Tremblay A, Bouchard C, et ai. Postprandial triglyceride response in visceral obesity in men. Diabetes 1998; 47 : 953-60.

17.Raji A, seely EW, Arky RA, Simonson DC. Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J CHn Endocrinol Metab 2001; 86 : 5366-71.

18. Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM. Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endoci-inol Metab 1999; 84 : 2329-35.

19. Misra A, Vikram NK, Arya S, Pandey RM, Dhingra V, Chattcrjee A, et al. High prevalence of insulin resistance in poslpubertal Asian Indian children is associated with adverse lruncal body fat patterning, abdominal adiposity and excess body fat. Int Obes Relat Metab Disord 2004; 28 : 1217-26.

20. Misra A. Impact of ethnicity on body fat patterning in Asian Indians and Blacks: Relationship with insulin resistance. Nutrition 2003; 19: 815-6.

21. Misra A, Vikram NK. Insulin resistance syndrome (metabolic syndrome) and obesity in Asian Indians: evidence and implications. Nutrition 2004; 20 : 482-91.

22. Blackburn P, Lamarche B, Couillard C, Pascot A, Bergeron N, Prud'homme D, et al. Postprandial hyperlipidemia: another correlate of the "hypertriglyceridemic waist" phenotype in men. Atherosclerosis 2003; 171 : 327-36.

23. Sharman MJ, Gomez AL, Kraemer WJ, Volek JS. Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men. J Nutr 2004; 134 : 880-5.

24. Snehalatha C, Sivasankari S, Satyavani K, Vijay V, Ramachandran A. Postprandial hypertriglyceridaemia in treated type 2 diabetic subjects - the role of dietary components. Diabetes Res Clin Pract 2000; 48 : 57-60.

25.Ezenwaka CE, Kalloo R. Carbohydrate-induced hypertriglyceridaemia among West Indian diabetic and non diabetic subjects after ingestion of three local carbohydrate foods. Indian J Med Res 2005; 121 : 23-31.

26. Rutledge JC, Hyson DA, Garduno D, Cort DA, Paumer L, Kappagoda CT. Lifestyle modification program in management of patients with coronary artery disease: the clinical experience in a tertiary care hospital. J Cardiopulm Rehabil 1999; 19: 226-34.

27. Kobayashi J, Saito Y, Taira K, Hikita M, Takahashi K, BuJo H, et al. Effect of apolipoprotein E3/4 phenotype on postprandial triglycerides and retinyl palmitate metabolism in plasma from hypcrlipidemic subjects in Japan. Atherosclerosis 2001 ; 154 : 539-46.

28. Jang Y, Kirn JY, Kirn OY, Lee JE, Cho II, Ordovas JM, et al. The -1131T C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in nonobese Korean men. Am J Clin Nutr 2004; 80 : 832-40.

29. Agren JJ, Valve R, Vidgren H, Laakso M, Uusitupa M. Postprandial Iipemic response is modified by the polymorphism at codon 54 of the fatty acid-binding protein 2 gene. Arterioscler Thromb Vase Biol 1998; 18 : 1606-10.

30. Laplante M, Sell H, MacNaul KL, Richard D, Berger JP, Deshaies Y. PPAR-gamma activation mediates adipose depotspecific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion. Diabetes 2003; 52 : 291-9.

Anoop Misra*, Jasjeet Singh Wasir & Naval K. Vikram

*For correspondence: Department of Medicine, All India Institute of Medical Sciences, New Delhi 110029, India

e-mail: anoopmisra@metabolicresearchindia.com

Copyright Indian Council of Medical Research Jan 2005
Provided by ProQuest Information and Learning Company. All rights Reserved