© 1995 American Heart Association, Inc.
Articles |
Relation Between Insulin Resistance, Hyperinsulinemia, Postheparin Plasma Lipoprotein Lipase Activity, and Postprandial Lipemia
From the Department of Medicine, Stanford University School of Medicine, and the Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Palo Alto, Calif.
Correspondence to Gerald Reaven, Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, 3801 Miranda Ave (182-B), Palo Alto, CA 94304.
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Abstract |
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Abstract We examined the relation between insulin resistance, plasma glucose and insulin responses to meals, lipoprotein lipase (LPL) activity, and postprandial lipemia in a population of 37 healthy nondiabetic individuals. Plasma glucose and insulin concentrations were determined at frequent intervals from 8 AM through midnight (breakfast at 8 AM and lunch at noon); resistance to insulin-mediated glucose disposal was determined by measuring the steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of glucose, insulin, and somatostatin; LPL activity was quantified in postheparin plasma; and postprandial concentrations of triglyceride (TG)-rich lipoproteins were assessed by measuring the TG and retinyl palmitate content in plasma and the Svedberg flotation index (Sf) >400 and Sf 20 to 400 lipoprotein fractions. Significant simple correlation coefficients were found between various estimates of postprandial lipemia and SSPG (r=.38 to .68), daylong insulin response (r=.37 to .58), daylong glucose response (r=.10 to .39), and LPL activity (r=-.08 to -.58). However, when multiple regression analysis was performed, only SSPG remained independently associated with both postprandial TG and retinyl palmitate concentrations. These data provide evidence that insulin resistance plays an important role in regulating the postprandial concentration of TG-rich lipoproteins, including those of intestinal origin.
Key Words: insulin resistance • hyperinsulinemia • intestinal lipoproteins • postheparin lipoprotein lipase activity • postprandial lipemia
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Introduction |
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There is considerable evidence that resistance to insulin-mediated glucose disposal and compensatory hyperinsulinemia are involved in the regulation of hepatic VLDL triglyceride (TG) secretion and fasting plasma TG concentration in animals and humans.1 2 3 4 5 However, much less is known as to the relation, if any, between insulin resistance, compensatory hyperinsulinemia, and postprandial lipemia. The potential importance of this issue stems from two lines of research. In 1979, Zilversmit6 raised the possibility that postprandial lipemia might play an important role in the pathogenesis of coronary heart disease (CHD), and later studies have provided substantial support for this hypothesis.7 8 9 10 11 12 An entirely different line of investigation has led to the suggestion that resistance to insulin-mediated glucose disposal and/or compensatory hyperinsulinemia may also increase the risk of CHD.13 The present study attempted to join these two lines of investigation by evaluating the association between insulin resistance and postprandial lipemia. In so doing, we thought it important to differentiate the postprandial response of TG-rich lipoproteins of intestinal origin from that of TG-rich lipoproteins derived from the liver.14 Furthermore, given the important role played by lipoprotein lipase (LPL) in the catabolism of TG-rich lipoproteins and the recent evidence that LPL activity is decreased in insulin-resistant subjects,15 we also thought it necessary to measure postheparin LPL (PHLPL) activity in this study.
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Methods |
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The study was approved by the Stanford Human Subjects Committee, and each research volunteer gave written, informed consent before entering the study. The experimental population consisted of 37 healthy, nondiabetic subjects who had responded to newspaper advertisements describing our experimental goal. There were 21 men and 16 women with a mean age of 59 years (range, 36 to 74 years) and a mean body mass index of 26.9 kg/m2 (range, 20.7 to 32.0 kg/m2). All volunteers were in general good health as assessed by medical history, physical examination, and routine blood tests, including a standard oral glucose tolerance test, and none of the research subjects were receiving any medication known to affect carbohydrate or lipoprotein metabolism. Volunteers were admitted to the Stanford General Clinical Research Center the evening before the studies. They abstained from alcohol and performed no heavy exercise for 48 hours before being tested.
Resistance to insulin-mediated glucose disposal was determined by a modification16 of the insulin suppression test.17 Each research subject received a continuous infusion of somatostatin (5 µg/min IV), insulin (25 mU · m-2 · min-1), and glucose (240 mg · m-2 · min-1) via an indwelling polytetrafluoroethylene catheter in a superficial antecubital vein. Venous blood samples were obtained from a similar catheter inserted in a contralateral antecubital vein kept open with a 0.9% NaCl infusion containing 20 meq/L KCl. The continuous infusion was given for 180 minutes, and blood was obtained before and at 30, 60, 90, 120, 150, 160, 170, and 180 minutes after starting the infusion for measurement of plasma glucose and insulin. The mean value of the four measurements made during the last 30 minutes of the test was used to calculate the steady-state plasma insulin concentration and steady-state plasma glucose (SSPG) concentration. Since the steady-state plasma insulin levels are similar in all subjects, the SSPG concentration provides a measurement of insulin-mediated glucose disposal: the higher the SSPG, the more insulin resistant the research subject; the lower the SSPG, the more insulin sensitive the subject.
Postprandial glucose, insulin, and lipoprotein metabolism was evaluated as follows. All subjects were served equicaloric test meals, containing (as percent of total calories) approximately 15% protein, 45% fat, and 40% carbohydrate. Subjects were given breakfast at 8 AM (20% of daily calories) and lunch at noon (40% of daily calories). After breakfast and lunch the subjects consumed only water or noncaloric decaffeinated beverages until the end of the study at midnight. Vitamin A (Aquasol A, Astra Pharmaceutical Products, Inc) 60 000 U/m2 body surface area was also given with lunch.
Blood was withdrawn at hourly intervals from 8 AM to 6 PM and then every 2 hours until midnight. After separation, aliquots of plasma were either stored frozen for subsequent measurement of glucose,18 insulin,19 and TG20 concentrations or were subjected to sequential ultracentrifugations as follows. Three milliliters of fresh plasma from each time point were overlaid with 2.2 mL 0.9% NaCl and ultracentrifuged at 100 000g for 44 minutes at d<1.006 g/mL and 15°C in a 50.3 rotor to float lipoprotein particles of Svedberg flotation index (Sf) >400. The infranatant from the original separation was overlaid with 1.15% KBr and subjected to ultracentrifugation using the same rotor with 39 000 rpm at d=1.006 g/mL and 10°C for 100 000g for 15 hours, and the top layer obtained was defined as the Sf 20 to 400 fraction. Samples were processed as quickly as possible in the laboratory under subdued light. The Svedberg flotation index is an operational index calculated from the density, viscosity of plasma, and the total centrifugation force (gravityxtime) necessary to float a particle to the top by analytical ultracentrifugation. In the postprandial state, the Sf >400 lipoprotein fraction contains predominantly chylomicrons and large VLDL particles, whereas the Sf 20 to 400 lipoprotein fraction contains VLDL particles as well as chylomicron remnants.
Aliquots of plasma and Sf >400 and Sf 20 to 400 fractions were either used for measurement of TG concentration or extracted by chloroform/methanol (2:1; Folch's solution) by using a high-performance liquid chromatography (HPLC)–grade solvent. A known quantity of retinyl acetate (250 to 500 ng) was added to each sample before extraction as an internal standard. Extracted material was dried under a nitrogen stream, reconstituted in Folch's solution, and separated and quantified by HPLC at 326 nm using a reversed-phase Supelcosil LC-8 column (25x4.6 mm inner diameter) with 100% methanol as the mobile phase at a flow rate of 1.75 mL/min to separate retinyl alcohol and retinyl ester. Since 80% of the retinyl ester is represented by retinyl palmitate (RP), all results are presented as RP concentrations. Standard curves were created for RP, with the concentrations of this compound being calculated by using a molar extinction coefficient of 52 275 at 326 nm. The interassay coefficient of variance of plasma RP in our laboratory is 8%; isolated lipoprotein fractions have a smaller interassay variance of 5%. The intra-assay variance of 10 repeated injections of retinyl acetate is 2%. When vitamin A is given with lunch at noon (4 hours after a standard breakfast), the peak appearance of RP in plasma occurs 2 to 4 hours after lunch, and the majority of RP is present in the Sf >400 fraction throughout most of the 10-hour period of measurement, with very little RP present in the Sf <20 fraction until the end of the study (the 12th hour).
To assess LPL activity on a separate day, after overnight fasting each subject was given a bolus injection of heparin (100 U/kg IV) to release lipases into the circulation. Blood was drawn before the injection and 30 and 45 minutes later. Although total postheparin lipolytic activity peaks at 10 minutes after the injection, PHLPL activity was maximal at 30 minutes, and this plateau continued until 45 minutes. The results presented were based on measurement of the 30-minute postheparin samples. Total lipolytic activity was determined by using a [3H]triolein emulsion prepared according to Nilsson-Ehle et al21 with a final TG concentration of 2 mmol/L, and 50 to 100 µL of a sixfold-diluted postheparin plasma was added to 100 µL of [3H]TG emulsion and incubated for 30 minutes at 37°C. The [3H]nonesterified fatty acids released were extracted and separated from the [3H]TG substrate as described by Nilsson-Ehle et al,21 and radioactivity was assessed by a ß-scintillation spectrometer. In order to distinguish the activity of PHLPL from that of hepatic lipase, a high salt concentration (1 mol/L NaCl) was employed in a separate incubation to inhibit PHLPL so that only hepatic lipase activity was measured. The LPL activity was then determined by the difference between the total lipolytic activity and the hepatic activity. The results were equilibrated to an internal standard and expressed as micromoles of free fatty acids released per hour per milliliter of postheparin plasma. The coefficients of variation for the measurements of the lipoprotein and hepatic lipase assays were 4.3% and 4.2%, respectively.
Statistical Analysis
Results are expressed as mean±SEM, and statistical evaluation
was performed with the STATISTICAL ANALYSIS SYSTEM
program (SAS Institute) using the generalized linear models procedure.
Total responses of variables measured over time were calculated as
total area under the curve by the trapezoidal methods. Because several
of the metabolic variables were not normally distributed, Spearman
correlation coefficients were calculated to determine the relation
among these variables. Multiple regression analysis was also
performed to adjust for the confounding effects of age, gender, and
obesity.
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Results |
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The mean data for all 37 subjects are shown in Figs 1 through 3
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Fig 1 shows the plasma glucose and insulin
concentrations from 8 AM through midnight. Plasma TG
concentrations from 8 AM through midnight and
postprandial TG concentrations in the Sf >400 and
Sf 20 to 400 lipoprotein fractions from noon through
midnight are seen in Fig 2, and Fig 3
shows the RP content in plasma and the Sf >400 and
Sf 20 to 400 lipoprotein fractions from noon through
midnight. SSPG was 9.0±0.7 mmol/L (mean±SEM; range, 2.2 to 19.6
mmol/L).
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SSPG was highly correlated with postprandial TG and RP concentrations
in plasma and in both the Sf >400 and Sf 20 to
400 lipoprotein fractions (Table 1). In addition,
statistically significant correlation coefficients were identified
between postprandial TG and RP concentrations and the daylong plasma
insulin response. In general, daylong glucose response was also
significantly correlated with fasting and postprandial TG and RP
concentrations, but the relations identified were weaker compared with
SSPG and daylong plasma insulin, and the correlations between daylong
glucose and the TG and RP responses were not always significant.
Significant negative correlations were found between PHLPL activity and
fasting and postprandial TG and RP levels, with the exception of the
lack of a relation between PHLPL activity and RP concentration in the
Sf 20 to 400 lipoprotein fraction. Compared with SSPG and
daylong plasma insulin concentration, the relation between PHLPL
activity and the postprandial response of intestinal lipoproteins was
weaker in most instances.
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Since SSPG (insulin resistance) and the daylong insulin response were
statistically correlated (r=.82) and are metabolically
closely related, these variables were entered separately in the
multiple regression analysis with sex, age, body mass index,
glucose response, and PHLPL activity as independent variables. SSPG was
the most consistent independent predictor of postprandial TG and RP
concentrations (Table 2), and the only independent
variable in the model significantly associated with the postprandial
response of TG-rich lipoproteins of intestinal origin in every
instance. Although PHLPL activity was an independent predictor of
postprandial TG concentrations, there were no significant independent
relations between PHLPL activity and RP concentrations in either plasma
or the two TG-rich lipoprotein fractions. It can also be seen that age
was independently associated to some degree with the various measures
of postprandial lipemia.
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Table 3 shows the results of replacing SSPG with the
daylong insulin response in the regression model. It is apparent that
the results are very similar to those in Table 2
in that the insulin
response was essentially equal to SSPG as an independent predictor of
all the lipid and lipoprotein variables. As before, PHLPL activity was
independently associated with postprandial TG concentrations but not
with any measure of RP response. Finally, age was again shown to be
independently associated with some of the postprandial changes in
lipoprotein metabolism.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The results of this study show that resistance to insulin-mediated glucose disposal (as quantified by determining the SSPG during the insulin suppression test) was an independent predictor of degree of postprandial lipemia, and this was the case when measurements were made of either the concentration of all TG-rich lipoproteins or only those of intestinal origin. It should be emphasized that this investigation was conducted in 37 nondiabetic individuals with a wide range of initial plasma TG concentrations, and the measurements were made in response to conventional meals. Thus, it seems reasonable to suggest that the results of these studies are applicable to the population at large.
Since there are ample data showing that the plasma insulin response is highly correlated with degree of insulin resistance,22 23 the fact that postprandial TG and RP responses correlated with either insulin resistance or plasma insulin concentration was not surprising. Although Weintraub and associates24 did not measure insulin resistance, they did investigate the relation between plasma insulin concentration and degree of postprandial lipemia in 15 normal subjects. In their study, fasting plasma insulin was correlated with the postprandial increase in the nonchylomicron fraction (r=.53, P=.52), but they saw no direct relation between the plasma insulin concentration 2 hours after their test meal and the degree of postprandial lipemia. On the other hand, the test meal was given in the morning in their study, and consisted primarily of fat (65% of total calories). Since the measurements in the present study were made after lunch and both the breakfast and lunch meals consumed contained substantially more carbohydrate, we believe this to be the most likely explanation for why the association between insulin resistance and/or hyperinsulinemia and postprandial lipemia was more pronounced in our study. We also studied more than twice as many patients than did Weintraub et al (37 versus 15), and this may also have contributed to the differences in the results of the two studies.
The relation between PHLPL activity and the degree of postprandial lipemia is more complicated, and it is not immediately apparent why LPL activity was an independent predictor of the TG but not the RP response, whereas SSPG predicted both responses. By implication, these results indicate that clearance of TG-rich lipoproteins of intestinal origin was not regulated by differences in PHLPL activity in this patient population but only by variations in insulin resistance and/or insulin secretory capacity. In support of this notion is evidence that the higher the plasma insulin response to a meal, the greater will be the postprandial increase in concentration of TG-rich lipoproteins of intestinal origin.25 One possible explanation for this finding is that the more insulin resistant the individual and the higher the insulin response to a meal, the greater will be the stimulation of hepatic VLDL TG secretion. In this situation, it might be predicted that this would result in a prolongation of the removal of newly secreted intestinal lipoproteins from plasma. In support of this view, we have shown26 that low-fat, high-carbohydrate diets in insulin-resistant diabetic patients increase plasma postprandial insulin concentration, hepatic VLDL TG secretion, and postprandial levels of intestinal lipoproteins. Obviously, this explanation requires further evaluation, but our inability to definitively state why PHLPL activity was not an independent predictor of postprandial intestinal lipoprotein concentration should not obscure the fact that insulin resistance and postprandial insulin response were.
Although not the goal of this study, the role of plasma TG concentration as a risk factor for CHD should be addressed. It has been argued that hypertriglyceridemia is not an independent risk factor for CHD.27 28 However, it has been suggested that this interpretation is confounded by the statistical method used and the high degree of interindividual and intraindividual variability seen in the measurement of plasma TG concentrations.29 There is considerable evidence that insulin-resistant individuals will tend to be glucose intolerant, hyperinsulinemic, hypertensive, hypertriglyceridemic, and have smaller and denser LDL particles and higher concentrations of plasminogen activator inhibitor–1; each of these changes has been shown to increase the risk of CHD.13 30 The link between plasma TG concentration and CHD may also be due to the associated changes in postprandial lipemia.8 9 10 11 12 In this context, the association between insulin resistance and postprandial lipemia shown in this study further emphasizes the suggestion that resistance to insulin-mediated glucose disposal plays a central role in the etiology of CHD.
In conclusion, the present results show that resistance to insulin-mediated glucose disposal and/or compensatory hyperinsulinemia are predictors of the postprandial lipemic response to meals, whether assessed by the plasma concentrations of all TG-rich lipoprotein or only those of intestinal origin. PHLPL activity was also shown to be an independent predictor of postprandial triglyceride levels, but its influence was much less apparent when only TG-rich lipoproteins of intestinal origin were examined. These results provide evidence for another possible link between insulin resistance and/or compensatory hyperinsulinemia and CHD.
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Acknowledgments |
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This study was supported by research grants from the National Institutes of Health (HL-08506 and RR00070).
Received September 21, 1994; accepted December 7, 1994.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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1. Reaven GM, Lerner RL, Stern MP, Farquhar JW. Role of insulin in endogenous hypertriglyceridemia. J Clin Invest. 1967;46:1756-1767.
2. Olefsky JM, Farquhar JW, Reaven GM. Reappraisal of the role of insulin in hypertriglyceridemia. Am J Med. 1974;57:551-560. [Medline] [Order article via Infotrieve]
3. Tobey TA, Greenfield M, Kraemer F, Reaven GM. Relationship between insulin resistance, insulin secretion, very low density lipoprotein kinetics and plasma triglyceride levels in normotriglyceridemic man. Metabolism. 1981;30:165-171. [Medline] [Order article via Infotrieve]
4. Garg A, Helderman JH, Koffler M, Ayuso R, Rosenstock J, Raskin P. Relationship between lipoprotein levels and in vivo insulin action in normal young white men. Metabolism. 1988;37:982-987. [Medline] [Order article via Infotrieve]
5. Reaven GM, Risser TR, Chen Y-DI, Reaven EP. Characterization of a model of dietary-induced hypertriglyceridemia in young, non-obese rats. J Lipid Res. 1979;20:371-378. [Abstract]
6.
Zilversmit DB. Atherogenesis: a postprandial
phenomenon. Circulation. 1979;60:473-485.
7.
Stender S, Zilversmit DB. Comparison of cholesteryl
ester transfer from chylomicrons and other plasma lipoproteins to aorta
intima-media of cholesterol-fed rabbits. Arteriosclerosis. 1982;2:493-499.
8. Simmons LA, Sweyer T, Simons J, Bernstein L, Mock P, Poonia NS, Balasubramaniam S, Baron D, Branson J, Morgan J, Roy P. Chylomicrons and chylomicron remnants in coronary artery disease: a case-control study. Atherosclerosis. 1987;65:181-189. [Medline] [Order article via Infotrieve]
9. Simpson HS, Williamson CM, Olivecrona T, Pringle S, Maclean J, Lorimer AR, Bonnefous F, Bogaievsky Y, Packard CJ, Shepherd J. Postprandial lipemia, fenofibrate and coronary artery disease. Atherosclerosis. 1990;85:193-202. [Medline] [Order article via Infotrieve]
10.
Groot PHE, van Stiphout WAHJ, Krauss XH, Jansen H, van
Tol A, van Ramshorst E, Chin-On S, Hofman A, Cresswell SR, Havekes L.
Postprandial lipoprotein metabolism in normolipidemic men with and
without coronary artery disease. Arterioscler
Thromb. 1991;11:653-662.
11.
Patsch JR, Miesenb
ck G, Hopferwieser T,
Hÿhlberger V, Knapp E, Dunn JK, Gotto AM, Patsch W. Relation of
triglyceride metabolism and coronary artery disease: studies in the
postprandial state. Arterioscler Thromb. 1992;12:1336-1345.
12.
Karpe F, Bard JM, Steiner G, Carlson LA, Fruchart JC,
Hamsten A. HDLs and alimentary lipemia: studies in men with previous
myocardial infarction at young age. Arterioscler
Thromb. 1993;13:11-22.
13. Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37:1595-1607. [Abstract]
14. Chen Y-DI, Reaven GM. Intestinally-derived lipoproteins: metabolism and clinical significance. Diabetes Metab Rev. 1991;7:191-208. [Medline] [Order article via Infotrieve]
15.
Pollare T, Bessby B, Lithell H. Lipoprotein lipase activity in
skeletal muscle is related to insulin sensitivity.
Arterioscler Thromb. 1991;11:1192-1203.
16.
Harano Y, Ohgaku S, Hidaka H, Haneda K, Kikkawa R,
Shigeta Y, Abe H. Glucose, insulin and somatostatin infusion for the
determination of insulin sensitivity. J Clin Endocrinol
Metab. 1977;45:1124-1127.
17. Shen SW, Reaven GM, Farquhar JW. Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest. 1970;49:2151-2160.
18. Kadish AH, Litle RL, Sternberg JC. A new and rapid method for determination of glucose by measurement of rate of oxygen consumption. Clin Chem. 1968;14:116-131. [Abstract]
19. Hales CN, Randle PJ. Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963;88:137-146. [Medline] [Order article via Infotrieve]
20. Weiland O. Glycerol UV: method. In: Bergmeyer HV, ed. Methods of Enzymatic Analysis. New York, NY: Academic Press; 1974:1404-1408.
21. Nilsson-Ehle P, Tornquist H, Belfrage P. Rapid determination of lipoprotein lipase activity in human adipose tissue. Clin Chim Acta. 1972;72:383-390.
22.
Hollenbeck C, Reaven GM. Variations in insulin-stimulated
glucose uptake in healthy individuals with normal glucose tolerance.
J Clin Endocrinol Metab. 1987;64:1169-1173.
23. Reaven GM, Brand RJ, Chen Y-DI, Mathur AK, Goldfine I. Insulin resistance and insulin secretion are determinants of oral glucose tolerance in normal individuals. Diabetes. 1993;42:1324-1332. [Abstract]
24. Weintraub MS, Eisenberg S, Beslow JL. Different patterns of postprandial lipoprotein metabolism in normal, type IIa, type III, and type IV hyperlipoproteinemic individuals. J Clin Invest. 1987;79:1110-1119.
25. Chen Y-DI, Swami S, Skowronski R, Coulston A, Reaven GM. Differences in postprandial lipemia between patients with normal glucose tolerance and noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1993;76:172-177. [Abstract]
26. Chen Y-DI, Coulston MS, Zhou M-Y, Hollenbeck CB, Reaven GM. Why do low fat-high carbohydrate diets accentuate postprandial lipemia in patients with non-insulin-dependent diabetes mellitus? Diabetes Care. 1995;18:10-16. [Abstract]
27. Hulley SB, Rosenman RH, Bawol RD, Brand RJ. Epidemiology as a guide to clinical decisions: the association between triglyceride and coronary heart disease. N Engl J Med. 1980;302:1383-1389. [Abstract]
28.
Criqui MH, Heiss G, Cohn R, Cowan LD, Suchindran CM,
Bangdiwala S, Kritchevsky S, Jacobs DR, O'Grady HK, Davis CE. Plasma
triglyceride level and mortality from coronary heart disease. N
Engl J Med. 1993;328:1220-1225.
29.
Austin MA. Plasma triglyceride and coronary heart disease.
Arterioscler Thromb. 1991;11:2-14.
30. Reaven GM. Are triglycerides important as a risk factor for coronary disease? Heart Dis Stroke. 1993;2:44-48.[Medline] [Order article via Infotrieve]
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 J. Dallongeville, A. Harbis, P. Lebel, C. Defoort, D. Lairon, J.-C. Fruchart, and M. Romon The Plasma and Lipoprotein Triglyceride Postprandial Response to a Carbohydrate Tolerance Test Differs in Lean and Massively Obese Normolipidemic Women J. Nutr., August 1, 2002; 132(8): 2161 - 2166. [Abstract] [Full Text] [PDF]
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M D. Robertson, A. O Mason, and K. N Frayn Timing of vagal stimulation affects postprandial lipid metabolism in humans Am. J. Clinical Nutrition, July 1, 2002; 76(1): 71 - 77. [Abstract] [Full Text] [PDF]
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 M. Ai, A. Tanaka, K. Ogita, M. Sekinc, F. Numano, F. Numano, and G. M. Reaven Relationship between plasma insulin concentration and plasma remnant lipoprotein response to an oral fat load in patients with type 2 diabetes J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1628 - 1632. [Abstract] [Full Text] [PDF]
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H.-S. Kim, F. Abbasi, C. Lamendola, T. McLaughlin, and G. M Reaven Effect of insulin resistance on postprandial elevations of remnant lipoprotein concentrations in postmenopausal women Am. J. Clinical Nutrition, November 1, 2001; 74(5): 592 - 595. [Abstract] [Full Text] [PDF]
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E. Levy, D. Menard, E. Delvin, S. Stan, G. Mitchell, M. Lambert, E. Ziv, J. C. Feoli-Fonseca, and E. Seidman The Polymorphism at Codon 54 of the FABP2 Gene Increases Fat Absorption in Human Intestinal Explants J. Biol. Chem., October 19, 2001; 276(43): 39679 - 39684. [Abstract] [Full Text] [PDF]
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A. R. Sharrett, G. Heiss, L. E. Chambless, E. Boerwinkle, S. A. Coady, A. R. Folsom, and W. Patsch Metabolic and Lifestyle Determinants of Postprandial Lipemia Differ From Those of Fasting Triglycerides : The Atherosclerosis Risk in Communities (ARIC) Study Arterioscler Thromb Vasc Biol, February 1, 2001; 21(2): 275 - 281. [Abstract] [Full Text] [PDF]
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 A. Harbis, C. Defoort, H. Narbonne, C. Juhel, M. Senft, C. Latgé, B. Delenne, H. Portugal, C. Atlan-Gepner, B. Vialettes, et al. Acute Hyperinsulinism Modulates Plasma Apolipoprotein B-48 Triglyceride--Rich Lipoproteins in Healthy Subjects During the Postprandial Period Diabetes, February 1, 2001; 50(2): 462 - 469. [Abstract] [Full Text]
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M. Ai, A. Tanaka, K. Ogita, M. Sekine, F. Numano, F. Numano, and G. M. Reaven Relationship between Hyperinsulinemia and Remnant Lipoprotein Concentrations in Patients with Impaired Glucose Tolerance J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3557 - 3560. [Abstract] [Full Text]
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A. Nordoy, K. H. Bonaa, P. M. Sandset, J.-B. Hansen, and H. Nilsen Effect of {omega}-3 Fatty Acids and Simvastatin on Hemostatic Risk Factors and Postprandial Hyperlipemia in Patients With Combined Hyperlipemia Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 259 - 265. [Abstract] [Full Text] [PDF]
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F. Abbasi, T. McLaughlin, C. Lamendola, H. Yeni-Komshian, A. Tanaka, T. Wang, K. Nakajima, and G. M. Reaven Fasting Remnant Lipoprotein Cholesterol and Triglyceride Concentrations Are Elevated in Nondiabetic, Insulin-Resistant, Female Volunteers J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3903 - 3906. [Abstract] [Full Text]
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N. Mekki, M. A. Christofilis, M. Charbonnier, C. Atlan-Gepner, C. Defoort, C. Juhel, P. Borel, H. Portugal, A. M. Pauli, B. Vialettes, et al. Influence of Obesity and Body Fat Distribution on Postprandial Lipemia and Triglyceride-Rich Lipoproteins in Adult Women J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 184 - 191. [Abstract] [Full Text]
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J. J. Agren, R. Valve, H. Vidgren, M. Laakso, and M. Uusitupa Postprandial Lipemic Response Is Modified by the Polymorphism at Codon 54 of the Fatty Acid–Binding Protein 2 Gene Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1606 - 1610. [Abstract] [Full Text] [PDF]
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 P. J. Talmud, S. Hall, S. Holleran, R. Ramakrishnan, H. N. Ginsberg, and S. E. Humphries LPL promoter -93T/G transition influences fasting and postprandial plasma triglycerides response in African-Americans and Hispanics J. Lipid Res., June 1, 1998; 39(6): 1189 - 1196. [Abstract] [Full Text]
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C. M. Burchfiel, D. S. Sharp, J. D. Curb, B. L. Rodriguez, R. D. Abbott, R. Arakaki, and K. Yano Hyperinsulinemia and Cardiovascular Disease in Elderly Men : The Honolulu Heart Program Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 450 - 457. [Abstract] [Full Text] [PDF]
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A. Ritsch, H. Drexel, F. W. Amann, C. Pfeifhofer, and J. R. Patsch Deficiency of Cholesteryl Ester Transfer Protein : Description of the Molecular Defect and the Dissociation of Cholesteryl Ester and Triglyceride Transport in Plasma Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3433 - 3441. [Abstract] [Full Text]
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N. Mero, M. Syvanne, B. Eliasson, U. Smith, and M.-R. Taskinen Postprandial Elevation of ApoB-48-Containing Triglyceride-Rich Particles and Retinyl Esters in Normolipemic Males Who Smoke Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2096 - 2102. [Abstract] [Full Text]
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 B. Eliasson, M.-R. Taskinen, and U. Smith Long-term Use of Nicotine Gum Is Associated With Hyperinsulinemia and Insulin Resistance Circulation, September 1, 1996; 94(5): 878 - 881. [Abstract] [Full Text]
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G.M. Reaven and Y-D.I. Chen Insulin Resistance, Its Consequences, and Coronary Heart Disease : Must We Choose One Culprit? Circulation, May 15, 1996; 93(10): 1780 - 1783. [Full Text]
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C. M. Burchfiel, J. D. Curb, D. S. Sharp, B. L. Rodriguez, R. Arakaki, P.-H. Chyou, and K. Yano Distribution and Correlates of Insulin in Elderly Men : The Honolulu Heart Program Arterioscler Thromb Vasc Biol, December 1, 1995; 15(12): 2213 - 2221. [Abstract] [Full Text]
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