Differences in the Metabolism of Postprandial Lipoproteins After a High-Monounsaturated-Fat Versus a High-Carbohydrate Diet in Patients With Type 1 Diabetes Mellitus

From the Minneapolis Veterans Affairs Medical Center (A.G., W.R.S., S.J.P.) and the University of Minnesota, Minneapolis (A.P., J.P.B., W.R.S.).

Correspondence to Angeliki Georgopoulos, MD, Medicine Service 111M, VAMC, One Veterans Dr, Minneapolis, MN 55417. E-mail georg003{at}maroon.tc.umn.edu

	Abstract

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Abstract—There is little information comparing the effects of a high-monounsaturated (Mono)-fat versus a high-carbohydrate (CHO) diet in patients with type 1 diabetes mellitus. In the present study, the effects of these diets on a number of metabolic parameters were compared. Seventeen normolipidemic, nonobese patients with type 1 diabetes were provided with the diets for 4 weeks each in a randomized, crossover design. The percentages of Mono fat of the two diets were 25 Mono versus 9 CHO, with a corresponding total fat content of 40% versus 24% and a total CHO content of 45% versus 61%. At the end of each dietary period, parameters of glycemic control, coagulation factors, and fasting and postprandial lipoproteins were assessed. There were no differences in weight, glycemia, insulin dose, fasting lipid profile, or coagulation factors between the two diets. However, the metabolism of postprandial lipoproteins after a fat load differed; viz, after the Mono diet compared with the CHO diet, mean plasma triglyceride levels over 10 hours were higher (P=.0025, by repeated-measures ANOVA). The levels of triglyceride (P=.0045) and retinyl esters (P=.0046) in chylomicrons (S_f >400) and chylomicron remnants (S_f 100 to 400) (P=.0047 and P=.043, respectively), and the total particle number (apolipoprotein B levels) in chylomicron remnants (P=.001) and small, very low density lipoprotein (S_f 20 to 100, P=.016) were also higher. Our data suggest that in patients with type 1 diabetes, a CHO diet might be preferable to a Mono diet, since adherence to the former results in a lower number of circulating postprandial lipoprotein particles that are potentially atherogenic.

Key Words: postprandial lipoproteins • monounsaturated fat • carbohydrate • diet • type 1 diabetes mellitus

	Introduction

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Debate about the appropriate dietary prescription for patients with diabetes mellitus has been going on for many years.^{1 2 3} Based on recent studies in patients with type 2 diabetes mellitus and the paucity of data from patients with type 1 diabetes mellitus,³ new diet recommendations were issued by the American Diabetes Association, which suggest that 60% to 70% of calories be derived from the combination of CHO and Mono fat.⁴ The intake of CHO and fat was to be individualized on the basis of treatment goals but might include as much as 20% of calories from Mono fat with a corresponding decrease in the CHO content (to 40% to 50%). Since Sat and Poly fat intakes of 10% each are suggested, the total fat intake could be as high as 40%.⁴ The rationale is that in type 2 diabetes, high-Mono-fat diets compared with high-CHO diets result in reductions in glycemia, triglyceridemia, and insulinemia.^{5 6 7} The dietary recommendations, however, did not differentiate between the two types of diabetes.⁴ Since type 1 diabetes is not associated with the insulin resistance, obesity, and dyslipidemia frequently seen in type 2 diabetes, it is possible that the high-Mono-fat diets will have different effects in the two types of diabetes.

Patients with type 1 diabetes usually have normal fasting serum lipid levels, including triglycerides and HDL cholesterol.^{8 9} However, when compared with nondiabetic age- and sex-matched control subjects, type 1 diabetics have abnormalities in the metabolism of postprandial TRLs,¹⁰ viz, decreased clearance¹¹ and abnormal composition of the lipoproteins.¹² The postprandial rather than the fasting state predominates in most people, especially in patients with type 1 diabetes, who because of insulin administration run the risk of hypoglycemia when delaying or skipping a meal. Since postprandial lipoproteins, especially chylomicron remnants, are potentially atherogenic,^{13 14 15} it is important to compare the effects of diets in both the fasting and the postprandial state. We therefore undertook the present study to compare the effects of a high-Mono-fat and a high-CHO diet on fasting and postprandial lipoprotein levels.

Considering that the occurrence of cardiovascular events is frequently due to arterial occlusion and involves both atherosclerosis and thrombosis, we decided to also investigate whether either of the diets would adversely affect risk factors for thrombosis. This was especially of concern for diabetic subjects, since they have been reported to have an increased thrombotic tendency.¹⁶ The hypothesis tested in the present study was that in patients with type 1 diabetes, the high-Mono-fat diet when compared with the high-CHO diet would result in lower fasting and postprandial TRL levels, without adverse effects on other fasting lipoproteins, glycemic control, or thrombotic tendency.

	Methods

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Study Subjects and Experimental Protocol
Seventeen patients (9 men and 8 women) with type 1 diabetes (based on accepted criteria¹⁷ ) were studied. They were nonobese (mean±SD body mass index, 23.5±1.98 kg/m² body surface), normolipidemic subjects with normal liver, kidney, thyroid, and hematologic parameters and proteinuria <300 mg/24 h. Mean±SD age was 32.2±5.4 years (range, 22 to 41), and the average duration of diabetes was 14±9.6 years (range, 2 to 33). None of the subjects was taking medications affecting lipoprotein metabolism other than insulin, and two women were taking oral contraceptives. The lipoprotein measurements in these women were done at the same time of the contraceptive cycle in both diets. Patients remained on the same dose of medications throughout the study period. None of the study participants used alcohol on a regular basis.

At the screening visit, patients signed the consent form and were instructed by the dietitian on dietary record keeping. They were asked to provide a 7-day food record, which was used to calculate daily and meal caloric intake. Study participants were also asked to keep records of their blood glucose, insulin, and exercise. Participation in the study was arranged during time periods when exercise level was expected to vary little throughout the study.

A randomized, crossover design was used, with each dietary period lasting for 4 weeks. All food was prepared in the metabolic kitchen of the Minneapolis Veterans Administration Clinical Research Center and provided to the participants. A 3-day rotating menu plan was used. Prepared extra snacks were provided for periods of exercise or episodes of hypoglycemia.

The high-Mono-fat diet contained 40% total fat (25% Mono, 6% Poly, and 9% Sat), 45% CHOs, and 15% protein. The high-CHO diet contained 24% total fat (9% Mono, 6% Poly, and 9% Sat), 61% CHOs, and 15% protein. The Poly/Sat ratio of both diets was 0.67. All other nutrients including cholesterol (300 mg/d) and fiber (28 to 30 g/d) remained the same on both diets. Nutritional analysis of the two diets was carried out by the Decentralized Hospital Computer Program (DHCP) VA nutrition software program and verified by the National Nutrition Coordinating Center.

Glycemic control was evaluated by measurements of fasting plasma glucose, fructosamine (RoTAG, Roche Diagnostic Systems¹⁸ ), and HbA₁c measurements (Glyc-Affin, Isolab Inc). Blood glucose records were reviewed once or twice each week and adjustments made in insulin dose or time and caloric distribution of meals to avoid frequent hypoglycemia or sustained blood glucose levels >250 mg/dL. Since these records were not very reliable, they were not used to assess glycemic control. Patients visited the center twice or three times per week to be weighed and to pick up their meals. Subjects were asked to abstain from alcohol during the last 10 days of each diet period. During the last week of study, three blood samples for fasting (12 hours) blood glucose and plasma lipids (total, LDL, and HDL cholesterol; triglycerides; apoA-I; apoB; and lipoprotein[a]) were obtained from each subject. On the last day of each diet period, subjects were admitted to the Minneapolis VA Clinical Research Center for coagulation and postprandial lipoprotein studies.

Coagulation Studies
Blood was drawn with the double-syringe technique and placed in sodium citrate (0.129 mol/L) or EDTA tubes for determinations of factor VII, fibrinogen, TPA, PAI, and prothrombin fraction F1.2 levels. To assess the effect of partial vein occlusion (resulting in anoxic conditions) on these parameters, a pressure of 100 mm Hg was applied to the forearm for 10 minutes and another blood sample was collected for the same measurements. The venous occlusion test has been used to evaluate the fibrinolytic activity of endothelium and the release of TPA in patients with and without diabetes.^{19 20}

Postprandial Lipoprotein Studies
After a 12-hour fast, the patients ingested a "shake" containing egg white, granulated sugar substitute (Sweet `N Low), fruit flavor, 55 g of fat, and 60 000 IU of vitamin A per square meter of body surface area. In the initial 11 subjects, the fat used in the shake was similar in proportions to the preceding diet, ie, during the high-Mono-diet, the shake contained 62.5% Mono, 22.5% Sat, and 15% Poly fat; during the high-CHO diet it contained equal amounts of Mono and Sat fat (37.5% of each) and a smaller amount (25%) of Poly fat. Sucrose or other CHOs were not included in the shake, since they can increase the production of hepatic TRLs, and in this study we wanted to concentrate on the effects of the diets on the metabolism of mostly intestinal TRLs. Avoiding CHO intake was one of the reasons for using a shake rather than a regular meal. The other reason was the administration of an equal fat load to compare the effects of the two diets on metabolism (fat tolerance test). To rule out the possibility that any observed postprandial effects after each dietary period were due to the different fat compositions of the shake, we studied 6 additional subjects who ingested the same shake (62.5% Mono, 22.5% Sat, and 15% Poly) after both dietary periods. For all postprandial studies, blood was drawn before and at 2, 4, 5.5, 7, and 10 hours after ingestion of the shake. Plasma triglyceride determinations and isolation of three TRL subfractions (Svedberg flotation units >400, 100 to 400, and 20 to 100) were performed as described below. Triglyceride, apoB, and RE levels of the three isolated lipoprotein subfractions were determined over time. No other meal was consumed until the study was completed. To avoid hypoglycemia, 40% of the morning long-acting insulin dose was administered, and blood glucose was monitored at each blood sampling time. If the levels dropped below 60 mg/dL, a glass of fruit juice was administered. An angiocatheter flushed with saline was placed in an antecubital vein to avoid multiple venipunctures. No significant side effects occurred except epigastric fullness following ingestion of the shake and an occasional blood sugar drop necessitating the administration of fruit juice. Subjects were encouraged to drink water after each blood drawing.

Handling of Blood Samples
To avoid apoB degradation and lipid oxidation, blood samples for lipoprotein analysis were collected in tubes containing EDTA (1 mg/mL) and placed on ice. Plasma was separated by centrifugation at 10°C, and a cocktail containing 1 mg/mL DTPA, 0.02 mg/mL chloramphenicol, 12% -amino-n-caproic acid, 5% glutathione, 1% thimerosal, and 1% BHT was added. DTPA has been shown to be a more potent antioxidant than EDTA.²¹ TRL subfractions were kept at 4°C and analyzed within 1 to 2 weeks.

Determination of Fasting Lipid/Lipoprotein Parameters
Plasma triglyceride and total cholesterol were measured enzymatically with commercially available kits (Boehringer Mannheim Diagnostics). The CVs of these assays in our laboratory are 3.5% and 4%, respectively. HDL cholesterol was measured by heparin-manganese precipitation according to the Lipid Research Clinics Program protocol. ApoB, apo A-I, and lipoprotein(a) were determined nephelometrically by commercially available kits (Instar). These measurements are currently performed in the VA laboratory and are under quality control testing with the Northwest Lipid Research Laboratory in Seattle, Wash.

Isolation of Fasting and Postprandial TRLs
All isolations were performed under aseptic conditions within 48 to 72 hours of harvesting of plasma by salt density gradient ultracentrifugation using an SW 41 rotor according to the method of Lindgren as modified by Redgrave et al.²² Our recoveries are 86% to 94%. Three subfractions were isolated: S_f >400 lipoproteins · (4.5x10⁶ g · min) containing chylomicrons and chylomicron remnants; S_f 100 to 400 (31.2x10⁶ g · min) containing chylomicron remnants and "big" VLDL; and S_f 20 to 100 (152.0x10⁶ g · min) containing mostly VLDL and some remnants.

RE Determination
REs were measured in the isolated TRL subfractions, protected from light, after extraction with 4 mL ethanol, 5 mL hexane, and 4 mL water.²³ The hexane phase was evaporated, dissolved in ethanol, and injected into a Beckman high-performance liquid chromatograph using a Bondapak C₁₈ column. Retinyl acetate was used as an internal standard. The mobile phase was 100% methanol and the flow rate 2 mL/min. The amount of RE was calculated on the basis of retinyl palmitate standard read at 326 nm using Gold System software.

ApoB determinations in the lipoprotein subfractions were performed by electroimmunoassay recognizing both ApoB-100 and apoB-48²⁴ in Dr Alaupovic's laboratory at the Oklahoma Research Foundation. The CV for this assay is 5%.

Coagulation Factor Measurements
For determination of factor VII, blood samples were centrifuged (10 000g x10 minutes) at room temperature to obtain platelet-poor plasma. The total factor VII activity was assayed in a one-stage technique according to a modification of the method of Hardisty and MacPherson.²⁵ The results are expressed as a percentage of a standard plasma. The CV of the method is 4.8%. TPA and PAI were measured by ELISA using kits No. 00576 and No. 00577, respectively, from Asserachrom Diagnostica Stago (purchased through American Products). The CVs for these methods are 22% and 29%, respectively. Fibrinogen was measured by a modification of the Claus²⁶ method (CV of 3.6%). Prothrombin F1.2 was measured by ELISA using Baxter kit No. B4239–5 (CV of 11.5%).

Statistical Analysis
The fasting lipoproteins, coagulation parameters, glycemic control, and other clinical parameters were compared between the two diets by paired t test or the Wilcoxon sign rank test (for fructosamine).²⁷ Bonferroni adjustment for the 11 paired comparisons was applied to the probability level: =.05÷11, or .0045. Within each diet, the effect of anoxic conditions created by occlusion on the coagulation parameters was also compared by paired ttest (preocclusion and postocclusion). The response of plasma triglyceride and postprandial lipoprotein subfraction concentrations of triglyceride, apoB, and REs over time was analyzed by repeated-measures ANOVA²⁸ using a BMDP software program.

	Results

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The clinical parameters of the study participants at the end of the two diets are shown in Table 1 (mean±SD). There were no differences in weight or daily insulin dose between the two dietary periods. None of the parameters of glycemic control was significantly different between the two diets. HbA₁c was the same between the two dietary periods. Fasting blood glucose and fructosamine tended to be slightly but not significantly higher after the high-CHO than the high-Mono-fat diet.

Table 2 presents the fasting lipid and lipoprotein values at the end of the two dietary periods. Plasma total, HDL, and LDL cholesterol; triglycerides; apoA-I; apoB; and lipoprotein(a) were not significantly different between the two diets.

Coagulation Studies
As shown in Table 3, vein occlusion tended to increase TPA, factor VII, and fibrinogen values during both diets. The TPA response to occlusion was twofold to threefold, ie, on the low side of the expected threefold to 12-fold increase.²⁰ The preocclusion and postocclusion differences in fibrinogen were statistically significant on both diets, whereas preocclusion and postocclusion differences in factor VII reached statistical significance in the high-Mono-fat diet only. The observed differences were not due to an increase in hematocrit, which actually dropped by 2.4% after vein occlusion. Prothrombin fragment F1.2 levels were measured as a parameter of the state of thrombotic activation. They were at the upper limit of the normal reference range after the high-CHO diet and above the normal reference range after the high-Mono-fat diet. The differences between the two diets were not statistically significant due to considerable intrasubject variability.

In summary, our baseline results are consistent with an increased thrombotic tendency in patients with type 1 diabetes as shown by the low TPA and elevated prothrombin F1.2 levels compared with the normal reference values (Table 3). There were no significant differences between the two diets in any of the coagulation factors measured at baseline or after vein occlusion.

Postprandial Studies
As shown in Fig 1, the levels of triglyceride in plasma were consistently higher after the high-Mono-fat than the high-CHO diet for both postprandial protocols: ie, after ingestion of a shake with a different fat composition at the end of each dietary period (top panel, n=11) and a shake of the same fat composition after each dietary period (bottom panel, n=6). Therefore, for further analysis of the results, all data (n=17) were combined. As shown in Fig 2, the level of triglyceride in S_f >400 (chylomicrons and large remnants) and in S_f 100 to 400 (big VLDL and chylomicron remnants) increased after ingestion of the fat load (time effect P<.0005, repeated-measures ANOVA). In addition, a consistent diet effect was observed: postprandial triglyceride was higher at the end of the high-Mono-fat versus the high-CHO diet in plasma (P=.0025; S_f >400, P=.0045 and S_f 100 to 400, P=.0047). Triglyceride levels in S_f 20 to 100 (small VLDL and small chylomicron remnants) were not increased postprandially and tended to decrease after the high-CHO diet (Fig 2). After the high-Mono-fat diet, all postprandial triglyceride levels in this subfraction were higher than the corresponding values obtained after the high-CHO diet (P=.0134); they remained stable for 4 hours, increased at 5.5 hours, and were below baseline by 10 hours postprandially. There was significant intrasubject variability (P<.00005) in the postprandial triglyceride response to the fat load. The dietxsubject interaction was significant for all three subfractions (P=.0066 to P<.00005).

View larger version (16K): [in this window] [in a new window]   Figure 1. Mean±SEM triglyceride levels in plasma during the last day of the high-Mono-fat and high-CHO diets after ingestion of the same amount but different type of fat shake (top, n=11) and the same type of fat shake (bottom, n=6). Open circles indicate high-fat diet; solid circles, high-CHO diet.

View larger version (15K): [in this window] [in a new window]   Figure 2. Mean±SEM triglyceride levels in TRL subfractions (Sf >400, P=.0045; Sf 100 to 400, P=.0047; and Sf 20 to 100, P=.013, by repeated-measures ANOVA) after ingestion of the same amount of fat during the last day of each dietary period (n=17). Open circles indicate high-Mono-fat diet, solid circles, high-CHO diet.

We measured apoB in postprandial S_f 100 to 400 and S_f 20 to 100 lipoproteins to assess whether the differences in triglyceride measurements between the two diets were due to differences in circulating particle number or to differences in the triglyceride content of the circulating particles. ApoB levels represent particle number, since there is one apoB per particle. They were measured in the fasting state and at 2, 4, 5.5, 7, and 10 hours postprandially. The levels increased in S_f 100 to 400 for 7 hours postprandially on both diets (Fig 3). Fasting (P=.011) and postprandial (P=.0001) apoB levels in S_f 100 to 400 were higher after the high-Mono-fat diet than after the high-CHO diet. There was also significant intrasubject variability in the apoB levels in this subfraction as shown by the subjectxdiet interaction (P<.00005). In S_f 20 to 100, fasting apoB levels were not different, and they decreased postprandially after both diets (Fig 3). The postprandial apoB levels in this subfraction were higher after the high-Mono-fat than the high-CHO diet (P=.0158). ApoB measurements were not detectable in the majority of patients in S_f >400, because apoB in these particles represents 1% or less of the particle mass.

View larger version (15K): [in this window] [in a new window]   Figure 3. Mean±SEM apoB levels in TRL subfractions (Sf 100 to 400, P=.0001 and Sf 20 to 100, P=.0158, by repeated-measures ANOVA) after ingestion of the same amount of fat during the last day of each dietary period (n=17). Open circles indicate high-Mono-fat diet; solid circles, high-CHO diet.

To assess the effect of the two diets on the metabolism of intestinal lipoprotein particles, we measured RE levels over time in all three postprandial TRL subfractions. REs are markers of intestinal particles because of their metabolic properties; viz, after their incorporation into the chylomicrons, they are cleared by the liver without being resecreted as VLDL.²⁹ A small percentage of REs transfers to denser lipoproteins (ie, LDL) over time (4 hours; Reference 30³⁰ and our unpublished observations, 1994). Therefore, measurements of REs in plasma after 4 hours do not represent intestinal particles only and were not performed in this study. However, measurements of REs in postprandial TRL subfractions remain with the particle and are valid markers of intestinal particles.^{31 32} Our results (Fig 4) show that following the fat meal, REs increased in all three postprandial TRL subfractions (effect of time P<.00005). Intrasubject variability was also noted (P<.00005). The RE levels were higher after the high-Mono-fat diet than after the high-CHO diet in S_f >400 (P=.0046) and S_f 100 to 400 (P=.043). The peak times of RE levels were also later (7 versus 5.5 hours) after the high-Mono-fat than the high-CHO diet in both S_f>400 and S_f 100 to 400 (Fig 4). In S_f 20 to 100, RE levels were lower than in the other two subfractions. This is to be expected, since in the postprandial state most of the S_f 20 to 100 particles are generated by lipolysis of the other two subfractions. Because of this phenomenon, the levels of REs in this subfraction started to increase at 4 hours and persisted for 10 hours (Fig 4). The levels of REs in S_f 20 to 100 lipoproteins were not different between the two diets.

View larger version (14K): [in this window] [in a new window]   Figure 4. Mean±SEM RE levels in postprandial TRLs (Sf >400, P=.0046; Sf 100 to 400, P=.043; and Sf 20 to 100, P=.51, by repeated-measures ANOVA) after ingestion of the same amount of fat during the last day of each dietary period (n=17). Open circles indicate high-Mono-fat diet; solid circles, high-CHO diet.

In summary, postprandial triglyceride levels in plasma and all three TRL subfractions following ingestion of a fat load were lower after the high-CHO than the high-Mono-fat diet. RE levels in chylomicrons (S_f >400) and big chylomicron remnants (S_f 100 to 400) were also lower. In addition, the total particle number (apoB levels) in fasting and postprandial S_f 100 to 400 and in postprandial S_f 20 to 100 was lower after the high-CHO than after the high-Mono-fat diet.

	Discussion

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The present study compared the effects of a high-Mono-fat versus a high-CHO diet on fasting and postprandial lipoprotein levels, glycemic control, and coagulation factors in normolipidemic, nonobese patients with type 1 diabetes. Our data show that we were successful in maintaining similar body weights during both diets (Table 1). During the two diets there were no significant differences in parameters of glycemic control, although a tendency for higher fructosamine and fasting plasma glucose levels after the high-CHO diet was observed. It is possible that if we studied a larger sample, the difference in fructosamine or fasting plasma glucose would reach statistical significance. An initial increase in the daily insulin requirements was observed in some patients on the high-CHO diet, but by the last week of the study the daily insulin doses were not different between the two diets. A lack of differences between the two diets in fasting plasma lipid parameters was also found (Table 2). Indeed, the presence of elevated fasting apoB levels in the big VLDL subfraction (S_f 100 to 400) during the high-Mono-fat diet represents the only difference between the two diets observed in the fasting state. This could be due to either increased hepatic production of VLDL particles by oleic acid³³ or decreased clearance of the particles by the liver receptors.

There is a paucity of dietary studies in type 1 diabetes³ with which to compare our results. A study of six patients using a similar dietary comparison but only 10 days on each diet also showed no differences in fasting lipoprotein parameters and fasting plasma glucose but did show higher postprandial plasma glucose levels during a 24-hour period on the high-CHO versus the high-Mono-fat diet; no measurements of fructosamine or postprandial lipoproteins were provided.³⁴ Two more studies are reported in patients with type 1 diabetes, but their results are difficult to interpret, since they compared a low-Sat-fat, low-cholesterol, high-CHO diet with a high-Sat-fat, high-cholesterol diet.^{35 36}

Since diabetic patients have been reported to have an increased thrombotic tendency,¹⁶ we investigated whether one of the two diets could adversely affect the risk for thrombosis while improving the risk for atherosclerosis. We measured thrombotic factors that have been reported to be abnormal in diabetes, like TPA, factor VII, fibrinogen,^{37 38 39 40} and PAI,²⁰ and/or factors that have been reported to be affected by dietary manipulations, like factor VII⁴¹ and PAI.⁴² Prothrombin fragment F1.2 was measured as a parameter of the state of thrombotic activation. Our baseline results are consistent with an increased thrombotic tendency in patients with type 1 diabetes, on the basis of low TPA and elevated prothrombin F1.2 levels compared with the normal reference values (Table 3). This tendency was not different between the two diets under study.

On the basis of the lack of differences in clinical parameters, fasting lipid, and coagulation factors between the two diets described above, we would have concluded that either of the two study diets could be recommended for nonobese, normolipidemic patients with type 1 diabetes. However, the results of our postprandial lipoprotein studies show significant differences in the metabolism of fat between the two diets. Contrary to our hypothesis, the high-Mono-fat diet, when compared with the high-CHO diet, resulted in higher circulating postprandial TRL levels for a period of 10 hours. The elevated plasma triglyceride levels after the high-Mono-fat diet versus the high-CHO diet were due to increases in chylomicrons (S_f >400), chylomicron remnants, and VLDL (S_f 100 to 400 and S_f 20 to 100; Fig 2). The higher triglyceride levels in the last two subfractions after the high-Mono-fat diet represent increases in the lipoprotein particle number rather than in the size of the particle (Fig 3). The increased number of circulating lipoprotein particles after the high-Mono-fat diet was due to a mixture of intestinal and hepatic particles. There were more intestinal particles in the chylomicrons, remnants, and big VLDL, as shown by the elevated RE levels in S_f >400 and S_f 20 to 400 (Fig 4). Increased levels of hepatic rather than intestinal particles following the high-Mono-fat diet most likely accounted for the elevation in the small VLDL, as shown by the elevated apoB and triglyceride, but not the RE, levels in the S_f 20 to 100 particles (Figs 2 through 4).

The mechanism of the differences in the effect of the two diets on postprandial lipoprotein metabolism is not clear. It has been shown in nondiabetic subjects that the major effect of a diet on postprandial lipoprotein metabolism was the type of fat that was chronically fed and that Sat versus Poly fat increased the levels of postprandial lipoproteins.⁴³ A smaller effect of the acute fat load was also seen in this study, with the Sat versus Poly fat load resulting in higher levels of postprandial lipoproteins.⁴³ We kept the Poly/Sat ratio of the chronic and acute fat loads the same (0.67) to avoid any interference of the Sat fat with our findings. We also kept the -3 fatty acid levels low and similar in both diets (1.25 g/d in high-CHO versus 1.25 g/d in the high-Mono-fat diet). Finally, the studies in the last six patients, who received the same fat load, were carried out to differentiate between the chronic effect of the diet and the acute effect of the fat load.

On the basis of our postprandial studies, we can make two points. First, in both diets, similar results were observed when the test meal either corresponded to or did not correspond to the two different diets (Fig 1); therefore, the observed differences in postprandial lipoprotein metabolism were due to chronic effects of the two study diets and not to a short-term effect of the type of meal ingested. Second, the postprandial response to the diet could not be predicted by the fasting triglyceride levels. This is most likely due to the fact that the fasting triglycerides levels of these patients were not different between the two diets and were within the normal range. As shown in Fig 1 (lower panel), the last 6 patients studied had a slightly higher average fasting triglyceride level after the high-CHO diet, but their postprandial response was lower than the one seen after the high-Mono-fat diet.

Our results on glycemia, plasma levels of fasting lipoproteins, and postprandial triglyceride levels differ from some,^{5 6 7} but not all,^{44 45 46} studies in patients with type 2 diabetes, which have reported higher plasma triglyceride, glucose, and insulin levels after a high-CHO than a high-Mono-fat diet. In these studies, subfractionation of postprandial lipoproteins and measurements of apoB in TRL subfractions were not carried out. Therefore, the studies cannot differentiate higher plasma triglyceride levels due to the same number of circulating lipoprotein particles with higher triglyceride content from plasma triglyceride elevations due to an increased number of circulating lipoprotein particles. It is also noteworthy that the effect of high-CHO metabolism on postprandial glucose levels can be offset by concomitant high-fiber intake.⁴⁷

The present studies cannot exclude the possibility that there are differences in the response to the two diets between the two types of diabetes. Type 1 diabetes is present in younger people and is not associated with excessive insulin resistance, obesity, and dyslipidemia, which are frequently seen in type 2 diabetes. Age,⁴⁸ insulin resistance, and dyslipidemia could affect the metabolic response to a diet and could account for the differences between our results and those reported in patients with type 2 diabetes. Our study raises the question whether the dietary recommendations for the two types of diabetes may need to be different. However, since very little data comparing the effect of a high-CHO versus a high-Mono-fat diet on postprandial lipoproteins exist in type 2 diabetes, further studies may be needed before such a conclusion can be reached.

Our results are consistent with an impairment of postprandial fat clearance by the high-Mono-fat diet compared with a high-CHO diet, which cannot be predicted by changes in fasting triglyceride levels. Therefore, in patients with type 1 diabetes, a high-CHO diet could be more beneficial than a high-Mono fat-diet, since the former results in lower particle numbers of circulating chylomicron remnants, which are potentially atherogenic.^{12 13 14 49}

	Selected Abbreviations and Acronyms

 

CHO = carbohydrate CV = coefficient of variation HbA1c = glycosylated hemoglobin Mono = monounsaturated PAI = plasminogen activator inhibitor Poly = polyunsaturated RE = retinyl ester Sat = saturated TPA = tissue-type plasminogen activator TRL = triglyceride-rich lipoprotein

	Acknowledgments

 
This study was supported by a grant from the National American Diabetes Association (to A.G.). We wish to acknowledge the expert assistance of Xiaohong Jia, Laura Salvati, Patricia Frykholm, and the staff of the Special Diagnostic and Treatment Unit of the Minneapolis Veterans Affairs Medical Center.

Received December 29, 1995; accepted December 11, 1997.

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