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American Journal of Clinical Nutrition, Vol. 74, No. 5, 592-595, November 2001
© 2001 American Society for Clinical Nutrition

Original Research Communication

Effect of insulin resistance on postprandial elevations of remnant lipoprotein concentrations in postmenopausal women1,2,3

Hee-Sun Kim, Fahim Abbasi, Cynthia Lamendola, Tracey McLaughlin and Gerald M Reaven

From the Department of Medicine, Stanford University School of Medicine, California.

2 Supported by research grants HL-08506 and RR-00070 from the National Institutes of Health.

3 Address reprint requests to GM Reaven, Falk CURC Stanford Medical Center, 300 Pasteur Drive, Stanford, CA 94305. E-mail: greaven{at}cvmed.stanford.edu.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Questions remain as to why postmenopausal women are at a higher risk of coronary artery disease (CAD) than are premenopausal women. Studies have shown that plasma concentrations of remnant lipoproteins (RLPs) are elevated in patients with CAD and that increases in plasma RLP concentrations may be related to variations in insulin-mediated glucose disposal.

Objective: We sought to evaluate the possibility that postprandial accumulation of plasma RLPs will be accentuated in insulin-resistant, postmenopausal women.

Design: Postmenopausal women were divided into insulin-sensitive (n = 15) and insulin-resistant (n = 15) groups according to their steady state plasma glucose concentrations in response to a 180-min infusion of octreotide, insulin, and glucose. Plasma insulin, triacylglycerol, and RLP-cholesterol concentrations were measured either hourly (insulin) or every 2 h (triacylglycerol and RLP cholesterol) for 8 h, before and after breakfast (0800) and lunch (1200).

Results: By selection, insulin-resistant women had higher steady state plasma glucose concentrations than did insulin-sensitive women (10.8 ± 0.5 compared with 4.1 ± 5 mmol/L, respectively; P < 0.001), associated with higher fasting triacylglycerol (1.58 ± 0.04 compared with 1.00 ± 0.03 mmol/L; P = 0.01) and lower HDL-cholesterol (1.06 ± 0.08 compared with 1.34 ± 0.05; P = 0.01) concentrations. In addition, measurements of daylong concentrations of insulin, triacylglycerol, and RLP cholesterol were also significantly greater in insulin-resistant than in insulin-sensitive women (P < 0.001).

Conclusions: Postprandial accumulation of RLPs is accentuated in insulin-resistant, postmenopausal women. This may contribute to the increased risk of CAD in these individuals.

Key Words: Postmenopausal women • remnant lipoproteins • postprandial lipemia • coronary artery disease • CAD • insulin resistance • insulin sensitivity • insulin


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
It has been >20 y since Zilversmit (1) first introduced the notion that atherogenesis is a postprandial phenomenon and that the lipoprotein particles formed during the catabolism of triacylglycerol-rich lipoproteins are highly effective cholesterol-ester donors. Although a considerable period of time elapsed before much attention was given to the role of postprandial lipemia as a coronary artery disease (CAD) risk factor, articles published within the past decade have provided considerable support for the Zilversmit hypothesis (2–6). In a somewhat parallel fashion, our research group over the past few years has been exploring possible mechanisms to account for differences in the magnitude of postprandial lipemia. A relation between fasting plasma triacylglycerol concentrations and postprandial lipemia has been known for some time (7,8), but we have more recent evidence suggesting that resistance to insulin-mediated glucose disposal or compensatory hyperinsulinemia enhances the postprandial accumulation of triacylglycerol-rich lipoproteins of both endogenous and exogenous origin in patients with type 2 diabetes (9), in postmenopausal women (10), and in healthy volunteers (11).

The ability to study the relation between postprandial lipemia and various clinical syndromes and physiologic states has been significantly aided by the introduction of an assay method (12,13) for quantifying apolipoprotein (apo) E–rich lipoproteins (d <1.006 g/mL) by using an immunoaffinity gel mixture of antibodies to apo B-100 and apo A-1 coupled to Sepharose 4B (JIMRO, Tokyo). The characterization of the unbound lipoproteins isolated in this manner indicated that they represent chylomicron and VLDL remnants, collectively called remnant lipoprotein particles (RLPs). By using this technique, evidence was published showing that RLP concentrations were significantly higher in subjects with type 2 diabetes and impaired glucose tolerance (14) and in insulin resistant individuals with normal glucose tolerance (15) after they had fasted overnight. In addition, we also showed that postprandial concentrations of RLPs increased throughout the day in response to carbohydrate-enriched diets (16). The present study was conducted to compare daylong changes in these atherogenic lipoproteins in postmenopausal women, who were divided into insulin-resistant and insulin-sensitive subgroups, the former group being at highest risk of CAD.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The present study was approved by the Stanford Institutional Review Board and each volunteer gave written, informed consent before entering the study. Nondiabetic (17), postmenopausal women with a body mass index (in kg/m2) between 19 and 33 who were not taking any medication known to affect lipid metabolism were screened for enrollment in the study after they responded to an advertisement in a local newspaper. To qualify for further evaluation, volunteers were required to have completed a normal menopause >=12 mo previously. The number of participants receiving hormonal replacement therapy was comparable in the insulin-sensitive (n = 9/15) and insulin-resistant (n = 11/15) groups. In addition, results of a physical examination, hemogram, urinalysis, and routine biochemical tests had to be within the normal range. Subjects taking hormone replacement therapy continued to do so throughout the study.

Volunteers who satisfied these initial criteria were admitted to the General Clinical Research Center at Stanford Medical Center, and insulin-mediated glucose disposal was measured by the insulin-suppression test (18,19). After subjects had fasted overnight, intravenous catheters were placed in each arm. Blood was sampled from one arm for measurement of plasma glucose and insulin concentrations and from the contralateral arm for administration of test substances. Octreotide (Novartis, East Hannover, NJ) was administered at a rate of 0.27 µg·m-2·min-1 to suppress endogenous insulin secretion. Simultaneously, insulin and glucose were infused at 32 mU·m-2·min-1 and 217 mg·m-2·min-1, respectively. Blood was sampled for measurement of plasma glucose and insulin concentrations every 30 min for 150 min and then every 10 min until 180 min had elapsed. Insulin concentrations typically plateaued by 60 min, whereas glucose concentrations plateaued after 120 min. The 4 values obtained from 150 and 180 min were averaged and considered to represent the steady state plasma glucose (SSPG) and steady state plasma insulin (SSPI) concentrations achieved during the infusion. Because SSPI concentrations are similar in all individuals (qualitatively and quantitatively) and the glucose infusion rate was identical, the magnitude of the resultant SSPG concentration provides an accurate estimate of how effective insulin is in disposal of the infused glucose load, ie, the higher the SSPG, the more insulin resistant an individual. On the basis of the results of the insulin-suppression test, 15 insulin-sensitive women (SSPG concentrations <5.6 mmol/L) and 15 insulin-resistant women (SSPG >8.9 mmol/L) were enrolled in the present study. Volunteers who did not meet the requirements for either of these categories were not included.

After selection for inclusion in the study, all 30 subjects were admitted to the General Clinical Research Center of Stanford Medical Center. Blood was drawn at 0800 after subjects had fasted for 12 h overnight for measurement of plasma glucose, insulin, cholesterol, LDL-cholesterol, HDL-cholesterol, total cholesterol, and triacylglycerol concentrations. In addition, blood was drawn hourly for measurement of plasma glucose and insulin concentrations and every 2 h for measurement of plasma triacylglycerol and RLP-cholesterol concentrations from 0800 until 1600, after the subjects ingested a standard test breakfast (0800) and lunch (1200). The test meals contained (as percentage of total energy) 20% protein, 50% carbohydrate, and 30% fat. The energy intake of the test meals for each individual was calculated by using the Harris-Benedict equation (20), and the subjects received 20% of daily energy at breakfast and 40% at lunch.

Plasma glucose, insulin, total cholesterol, and triacylglycerol concentrations were measured as described previously (9–11). HDL was isolated by precipitation (21) and LDL cholesterol was calculated by the Friedewald equation (22). An immunosuppression assay was used to measure cholesterol in RLP cholesterol, as described previously (12–16). This method uses monoclonal antibodies to human apo B-100 and apo A-1 to remove most of the apo B– and A-1–containing particles (LDL, nascent VLDL, chylomicrons, and HDL), leaving behind chylomicrons and very low density RLPs that are enriched with apo E. Briefly, plasma (5 µL) was added to an immunoaffinity gel suspension containing the 2 monoclonol antibodies, the reaction mixture incubated at room temperature for 2 h on an RLP mixer, and aliquots of the supernatant fluid drawn for measurement of RLP-cholesterol concentrations.

Data are expressed as means ± SEs. The significance of the difference between baseline characteristics was evaluated by Student's nonpaired t test and the changes from 0800 to 1600 were determined by two-way analysis of variance, with the insulin group and time as the 2 variables. There was no significant group-by-time interaction and the calculated P values represent the daylong difference between the 2 groups (main effect of group).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Baseline characteristics of the insulin-resistant and insulin-sensitive groups are shown in Table 1Go. By selection, SSPG concentrations were almost 3-fold higher in the insulin-resistant women. Although the ages of the 2 groups were not significantly different, body mass index was higher in the insulin resistant women. In addition, triacylglycerol concentrations were higher and HDL-cholesterol concentrations lower in the insulin-resistant group. However, total and LDL-cholesterol concentrations were not significantly different between the 2 groups.


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  		TABLE 1. Baseline characteristics of insulin-sensitive and insulin-resistant postmenopausal women1
 
Daylong concentrations of plasma glucose and insulin are shown in Figure 1Go. Hourly plasma glucose concentrations were somewhat higher throughout the day in the insulin-resistant group and this difference was significant by two-way analysis of variance. The overall difference between the daylong insulin responses of the 2 groups was quantitatively much greater than was the difference in the glucose response and was also significant.



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  		FIGURE 1. Mean (± SE) plasma glucose and insulin concentrations of insulin-resistant ({circ}) and insulin-sensitive ({blacksquare}) women measured every hour from 0800 to 1600. Breakfast was served at 0800 and lunch at 1200.

 
Plasma triacylglycerol and RLP-cholesterol concentration responses to breakfast and lunch in the 2 groups are shown in Figure 2Go. Fasting values of both variables were higher in the insulin-resistant than in insulin-sensitive women before breakfast and remained so throughout the 8-h period of observation.



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  		FIGURE 2. Mean (± SE) plasma triacylglycerol and remnant lipoprotein (RLP)-cholesterol concentrations of insulin-resistant ({circ}) and insulin-sensitive ({blacksquare}) women measured every 2 h from 0800 to 1600. Breakfast was served at 0800 and lunch at 1200.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In a series of prospective studies in nondiabetic individuals, insulin resistance or hyperinsulinemia has been identified as increasing the risk of CAD (23–26). The role played by these abnormalities of insulin metabolism in the genesis of CAD is confounded by the fact that insulin-resistant or hyperinsulinemic individuals are often hypertriglyceridemic, with low HDL-cholesterol concentrations, smaller and denser LDL particles, and increased plasma concentrations of plasminogen activator inhibitor 1 (27–31). Because all of these associated changes have been identified as CAD risk factors (32–35), it is difficult to decide whether the increased CAD risk is due to insulin resistance per se; the compensatory hyperinsulinemia that characterizes insulin-resistant, nondiabetic subjects; or any of the cluster of abnormalities associated with insulin resistance or hyperinsulinemia. The results of the present study further complicate this issue by showing that daylong concentrations of RLPs are significantly greater in insulin-resistant than in insulin-sensitive individuals.

Given the evidence in support of a causal relation between postprandial lipemia and CAD (1–6), the present results showing the dramatic difference in daylong concentrations of RLPs between insulin-resistant and insulin-sensitive individuals is of substantial clinical relevance. For example, using a different technique, we previously showed that the more insulin resistant an individual and the higher the plasma insulin concentration, the greater the postprandial accumulation of triacylglycerol-rich lipoproteins (11). Furthermore, the low-fat, high-carbohydrate diets that are currently recommended to lower the risk of CAD (36) increase daylong plasma concentrations of insulin, triacylglycerol, and RLP concentrations more than do diets in which saturated fat is replaced with unsaturated fat (16). In light of the evidence that insulin resistance or hyperinsulinemia increases the risk of CAD (23–26) and the strong association between insulin resistance and RLP concentrations shown in this study, it seems reasonable to suggest that therapeutic interventions aimed at decreasing CAD in postmenopausal women take into account the possible effects of these recommendations on insulin action, daylong plasma insulin concentrations, and degree of postprandial lipemia.


   ACKNOWLEDGMENTS
 
We thank Elizabeth Leary, Pacific Biometrics, Inc, who graciously collaborated with the study and was responsible for measuring postprandial triacylglycerol and remnant lipoprotein concentrations.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Zilversmit DB. Atherogenesis: a postprandial phenomenon. Circulation 1979;60:473–85.[Abstract/Free Full Text]
  2. Simons LA, Dyer T, Simons J, et al. Chylomicrons and chylomicron remnants in coronary artery disease: a case-control study. Atherosclerosis 1987;65:181–9.[Medline]
  3. Simpson HS, Williamson CM, Olivecrona T, et al. Postprandial lipemia, fenofibrate and coronary artery disease. Atherosclerosis 1990;85:193–202.[Medline]
  4. Groot PH, van Stiphout WA, Krauss XH, et al. Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease. Arterioscler Thromb 1991;11:653–62.[Abstract/Free Full Text]
  5. Patsch JR, Miesenbock G, Hopferwieser T, et al. Relation of triglyceride metabolism and coronary artery disease studies in the postprandial state. Arterioscler Thromb 1992;12:1336–45.[Abstract/Free Full Text]
  6. Karpe F, Bard JM, Steiner G, Carlson LA, Fruchart JC, Hamstein A. HDLs and alimentary lipemia: studies in men and with previous myocardial infarction at young age. Arterioscler Thromb 1993;13: 11–22.[Abstract/Free Full Text]
  7. Nestel PJ. Relationship between plasma triglycerides and removal of chylomicrons. J Clin Invest 1964;43:943–9.
  8. Wilson DE, Chan I-F, Buchi KN, Horton SC. Postchallenge plasma lipoprotein retinoids: chylomicron remnants in endogenous hypertriglyceridemia. Metabolism 1985;34:551–8.[Medline]
  9. Chen Y-DI, Swami S, Skowronski R, Coulston A, Reaven GM. Differences in postprandial lipemia between patients with normal glucose tolerance and non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1993;76:347–51.[Abstract]
  10. Jeppensen J, Schaaf P, Jones C, Zhou MY, Chen YD, Reaven GM. Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women. Am J Clin Nutr 1997;65:1027–33.[Abstract/Free Full Text]
  11. Jeppesen J, Hollenbeck CB, Zhou M-Y, et al. Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. Arterioscler Thromb Vasc Biol 1995;15:320–4.[Abstract/Free Full Text]
  12. Campos E, Nakajima K, Tanaka A, Havel RJ. Properties of an apoliproprotein E-enriched fraction of triglyceride-rich lipoproteins isolated from human blood plasma with a monoclonal antibody to apoliproprotein B-100. J Lipid Res 1992;33:369–80.[Abstract]
  13. Leary ET, Wang T, Baker DJ, et al. Evaluation of an immunoseparation method for quantitative measurement of remnant-like particle-cholesterol in serum and plasma. Clin Chem 1998;44:2490–8.[Abstract/Free Full Text]
  14. Watanabe N, Taniguchi T, Taketoh H, et al. Elevated remnant-like lipoprotein particles in impaired glucose tolerance and type 2 diabetic patients. Diabetes Care 1999;22:152–6.[Abstract/Free Full Text]
  15. Abbasi F, McLaughlin T, Lamendola C, et al. Fasting remnant lipoprotein cholesterol and triglyceride concentrations are elevated in non-diabetic, insulin resistant, female volunteers. J Clin Endocrinol Metab 1999;84:3903–6.[Abstract/Free Full Text]
  16. Abbasi F, McLaughlin T, Lamendola C, et al. High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk. Am J Cardiol 2000;85:45–8.[Medline]
  17. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. 1998 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1998; 21(suppl):S5–22.
  18. Greenfield MS, Doberne L, Kraemer FB, Tobey TA, Reaven GM. Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes 1981;30:387–92.[Abstract]
  19. Pei D, Jones CNO, Bhargava R, Chen Y-DI, Reaven GM. Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin suppression test. Diabetologia 1994;37:843–5.[Medline]
  20. Harris JA, Benedict FG. A biometric study of basal metabolism in man. Washington, DC: Carnegie Institute of Washington, 1919. (Publication 1996;279.)
  21. Gidez LE, Miller GJ, Burstein M, Slagle S, Eder HA. Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure. J Lipid Res 1982;23:1206–23.[Abstract]
  22. Friedewald WT, Levy RI, Fredrikson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–501.[Abstract]
  23. Pyorala K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care 1979;2:131–41.[Abstract]
  24. Depres J-P, Lamarche B, Mauriege P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996;334:952–7.[Abstract/Free Full Text]
  25. Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab 1998;83:2773–6.[Abstract/Free Full Text]
  26. Zavaroni I, Bonini L, Gasparini P, et al. Hyperinsulinemia in a normal population as a predictor of non-insulin-dependent diabetes mellitus, hypertension, and coronary heart disease: the Barilla factory revisited. Metabolism 1999;48:989–94.[Medline]
  27. Reaven GM, Lerner RL, Stern MP, Farquhar JW. Role of insulin in endogenous hypertriglyceridemia. J Clin Invest 1967;46:1756–67.
  28. Olefsky JM, Farquhar JW, Reaven GM. Reappraisal of the role of insulin in hypertriglyceridemia. Am J Med 1974;57:551–60.[Medline]
  29. Laws A, Reaven GM. Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J Intern Med 1992;231:25–30.[Medline]
  30. Reaven GM, Chen Y-DI, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles. J Clin Invest 1993;92:141–6.
  31. Abbasi F, McLaughlin T, Lamendola C, Lipinska I, Tofler G, Reaven GM. Comparison of plasminogen activator inhibitor-1 concentration in insulin-resistant versus insulin-sensitive healthy women. Arterioscler Thromb Vasc Biol 1999;19:2818–21.[Abstract/Free Full Text]
  32. Miller GJ, Miller NE. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1975;1:16–9.[Medline]
  33. Castelli WP, Garrison RJ, Wilson PWF, Abbott RO, Kalonsdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study. JAMA 1986;256:2835–7.[Abstract]
  34. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998;81:7B–12B.[Medline]
  35. Juhan-Vague I, Thompson SG, Jespersen J. Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group. Arterioscler Thromb 1993;13:1865–73.[Abstract/Free Full Text]
  36. NCEP Expert Panel. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel On Detection, Evaluation, And Treatment of High Blood Cholesterol in Adults (adult Treatment Panel II). JAMA 1993;269:3015–302.[Medline]
Received for publication October 16, 2000. Accepted for publication March 1, 2001.




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