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Effect of a High-Carbohydrate Versus a High—cis-Monounsaturated Fat Diet on Blood Pressure in Patients With Type 2 Diabetes

¹ Division of Nutrition and Metabolic Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
² Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
³ Department of Kinesiology, Texas Christian University, Fort Worth, Texas
⁴ Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
⁵ Department of Internal Medicine, University of Minnesota, Minneapolis, Minnesota
⁶ Department of Medicine, University of California, San Diego, California
⁷ Veterans Affairs Medical Center, San Diego, California
⁸ Department of Internal Medicine, Stanford University, Stanford, California

Address correspondence and reprint requests to Abhimanyu Garg, MD, Professor and Chief, Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9052. E-mail: abhimanyu.garg{at}utsouthwestern.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
OBJECTIVE—To investigate whether blood pressure is different in type 2 diabetic patients on a diet rich in carbohydrates versus a diet rich in cis-monounsaturated fatty acids. Data on the dietary effects on these diets’ glucose and lipid metabolism have been previously published.

RESEARCH DESIGN AND METHODS—The study compared the effect of feeding 42 type 2 diabetic patients a carefully controlled isoenergic high-carbohydrate (high-carb; 55% energy as carbohydrate, 30% as fat, and 10% as monounsaturated fat) and high–monounsaturated fat (high-mono; 45% energy as fat, 25% as monounsaturated fat, and 40% as carbohydrate) diet for 6 weeks each in a four-center, randomized, cross-over study on blood pressure. Twenty-one patients continued the diet they received during the second phase for an additional 8 weeks.

RESULTS—According to repeated-measures ANOVA, blood pressure during the last 3 days of each phase was similar after 6 weeks of the high-carb and high-mono diets (systolic blood pressure: 128 ± 16 vs. 127 ± 15 mmHg, P = 0.9; diastolic blood pressure: 75 ± 7 vs. 75 ± 8 mmHg, P = 0.7). However, after 14 weeks of the high-carb diet (n = 13), there was a significant increase in blood pressure compared with 6 weeks of the high-mono diet (systolic blood pressure: 132 ± 13 vs. 126 ± 11 mmHg, P = 0.04; diastolic blood pressure: 83 ± 6 vs. 76 ± 7 mmHg, P = 0.002). After 14 weeks of the high-mono diet (n = 8), the reduction in blood pressure was not significant compared with 6 weeks of the high-carb diet (systolic blood pressure: 118 ± 14 vs. 121 ± 16 mmHg, P = 0.4; diastolic blood pressure: 71 ± 8 vs. 75 ± 10 mmHg, P = 0.3).

CONCLUSION—Although the exchange of carbohydrates with monounsaturated fats may not affect blood pressure in the short term, long-term consumption of a high-carbohydrate diet may modestly raise blood pressure in type 2 diabetic patients.

	INTRODUCTION

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It has been well established that replacing a high-carbohydrate diet with a diet rich in cis-monounsaturated fatty acids improves lipids and lipoproteins (1). Whether high—monounsaturated fat diets also improve blood pressure compared with high carbohydrate diets is controversial. Epidemiological studies show that cis-monounsaturated fat intake is higher in individuals with lower blood pressure (2,3).

The results of randomized intervention studies, which can determine cause and effect, in this area are conflicting. In a cross-over study in type 2 diabetic subjects, Rasmussen et al. (4) found that a high—monounsaturated fat diet lowered daytime ambulatory blood pressure but not auscultatory blood pressure compared with a high-carbohydrate diet. Lauszus et al. (5) reported a greater rise in 24-h ambulatory diastolic blood pressure with a high-carbohydrate diet than with a high—monounsaturated fat diet in women with gestational diabetes. However, Mensink et al. (6) found no difference in clinical blood pressure in normotensive subjects randomized to a high—monounsaturated fat or a high-carbohydrate diet. Three cross-over studies, two in type 2 diabetic subjects (7,8) and one in subjects with hyperlipidemia (9), also found no difference in 24-h ambulatory (7) or clinical (8,9) blood pressure on the two diets. These conflicting results could be due to a short study duration (21–36 days) in some studies (4,6,7,9); the small sample size of some cross-over (n = 10–15) (4,7) and parallel design (n = 27–47) (5,6) studies; the use of diets with large differences in saturated fat, fiber, or cholesterol content (4–6,8); or changes in patient body weight of >1 kg during the course of each diet (6). In addition, in one study, diets were only partially provided by the investigators (9).

Thus the purpose of the current investigation was to compare the long-term effects of carefully controlled isoenergic high-carbohydrate and high—monounsaturated fat diets prepared in metabolic kitchens on blood pressure and heart rate in a four-center, randomized, cross-over trial in type 2 diabetic subjects. The effects of these diets on glucose and lipid metabolism, the main aim of the study, have been published previously (10).

	RESEARCH DESIGN AND METHODS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 
We studied 42 patients (33 men and 9 women) with type 2 diabetes at the metabolic units of the Stanford University (Stanford, CA; n = 10), the University of Texas Southwestern Medical Center (Dallas, TX; n = 10), the University of Minnesota (Minneapolis, MN; n = 11), and the Veterans Affairs Medical Center (San Diego, CA; n = 11). The protocol for this study was approved by the institutional review boards of each university, and all patients gave informed written consent. Regarding ethnic background, 31 patients were white, 6 were African American, 4 were Hispanic, and 1 was Asian. Other subject characteristics (means ± SD) included age 58 ± 10 years (range 35–78), BMI 28.1 ± 2.9 kg/m² (range 23–33), systolic blood pressure 134 ± 18 mmHg (range 108–177), diastolic blood pressure 80 ± 9 mmHg (range 60–99), and heart rate 75 ± 8 bpm (range 60–100). Of the 11 subjects on blood pressure–lowering medication, 2 were on a diuretics, 5 were on a calcium channel blocker, 2 were on an ACE inhibitor, and 2 were on both an ACE inhibitor and a diuretic. The blood pressure medications of all these patients remained stable throughout the study.

A randomized, cross-over study was designed. The daily energy intake needed for weight maintenance was estimated by multiplying the calculated basal energy expenditure by an activity factor (11). All patients received each of the two isoenergic study diets (a high-carbohydrate [high-carb] and a high–cis-monounsaturated fatty acid [high-mono] diet) for 6 weeks each during phases 1 and 2. There was a median interval of 7 days between the two diet periods.

To assess the longer-term effects of diets, all patients were invited to consume the second diet for an additional 8 weeks (phase 2 extension) without interruption; 21 patients chose to do so. Of these, 8 patients continued on the high-mono diet and 13 continued on the high-carb diet, for a total duration of 14 weeks on the diet.

All meals were prepared in the metabolic kitchens. The patients ate at least one meal per day at the metabolic units on weekdays; the remaining food was supplied in packages to be consumed at home. To monitor compliance, the patients were instructed to bring back any unconsumed food, were interviewed by dietitians, and were weighed during their visits.

Diets
A set of four standard menus for each study diet was prepared for a 2,000-kcal intake. For a different energy level, all food items were adjusted accordingly. The high-carb diet provided 55% of total energy as carbohydrate and 30% as fat. The high-mono diet provided 45% of total energy as fat and 40% as carbohydrate. The saturated and polyunsaturated fats (10% of the total energy intake each), protein (15% of total energy), cholesterol (120 mg per 1,000 kcal), and sucrose (10% of the total energy) contents of the study diet were matched. The content of dietary fiber was kept proportional to the carbohydrate content (high-mono: 11 g/1,000 kcal; high-carb: 15 g/1,000 kcal). The patients were instructed to maintain their usual level of physical activity and salt intake. The energy intake was adjusted if needed to maintain constant body weight during the study.

Blood pressure and heart rate measurements
During the last 3 days of each phase, the patients were admitted to the inpatient metabolic unit of each center, where blood pressure and heart rate were measured daily using a mercury sphygmomanometer and palpation, respectively. The subjects did not engage in any physical activity or smoke. The blood pressure measurements were made on the left arm with the subjects sitting in a quiet room and were taken by the same staff. Systolic blood pressure was recorded in phase I and diastolic blood pressure in phase V Korotkoff (12). The mean of the measures taken during the last 3 days of each phase were used to compare differences among the different phases; three values were recorded in >75% of the times. Blood pressure and heart rate were also measured weekly during all the remaining weeks on an outpatient basis after a 5-min rest.

Statistical analyses
Repeated-measures ANOVA (performed using SAS Version 9.1) was used to assess the impact of the study diets, the order in which patients received the diets, and the site of study participation on blood pressure and heart rate for 6 weeks (phases 1 and 2) in 41 patients and for 14 weeks (phases 1, 2, and 2 extension) in 21 patients. Only 1 patient was dropped from the 6 weeks’ analysis for lack of blood pressure data. Least-square means contrasts were used to analyze the differences among the three phases (phases 1, 2, and 2 extension) when ANOVA revealed significant diet effects. The effects of possible confounding factors such as age, sex, and weight were also evaluated using repeated-measures ANOVA and covariance models; these covariates did not affect the blood pressure and heart rate response to the diets.

	RESULTS

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The compliance to both the study diets was excellent. The sites at which the patients were studied did not significantly affect the results, so combined results from all four centers are presented. Excluding the subjects who were on blood pressure–lowering medication did not affect the responses, so data on all the subjects are presented below.

Phases 1 and 2 (41 patients)
During the last 3 days of phases 1 and 2, energy intake (high-mono: 2,533 ± 366 kcal; high-carb: 2,528 ± 375 kcal; P = 0.8) and body weight (high-mono: 82.2 ± 11.8 kg; high-carb: 82.3 ± 12.2 kg; P = 0.8) were similar on the two diets.

The order in which the patients received the diets did not affect the results. After 6 weeks of the high-carb or high-mono diet, no difference was observed in systolic (128 ± 16 vs. 127 ± 15 mmHg; P = 0.9) or diastolic (75 ± 7 vs. 75 ± 8 mmHg, respectively; P = 0.7) blood pressure. Heart rate was slightly higher on the high-carb than on the high-mono diet (73 ± 8 vs. 71 ± 8 bpm; P = 0.06). Analysis of the weekly blood pressure collected during the outpatient follow-up (Fig. 1A and B) found no difference on the two diets (systolic blood pressure: P = 0.21; diastolic blood pressure: P = 0.12).

View larger version (20K): [in this window] [in a new window]   Figure 1— Weekly mean (±SE) systolic (A) and diastolic (B) blood pressure in 41 patients on the high-carb (, •) and high-mono (, ) diets during phases 1 and 2. , , outpatient values; •, , inpatient values.

The longer-term analysis of the effects of the study diets on systolic and diastolic blood pressure and heart rate during the last 3 days of phases 1, 2, and 2 extension in the subgroup of 21 patients showed a significant order-by-diet interaction (P = 0.007, 0.002, and 0.02, respectively), so the results are presented in the order in which the patients received the diets. Table 1 shows the results in 13 patients who received the high-mono diet for 6 weeks during phase 1 and the high-carb diet for 14 weeks during phases 2 and 2 extension. There was a significant diet effect for diastolic blood pressure (P = 0.003) and heart rate (P = 0.03). Diastolic blood pressure and heart rate were significantly higher (7 mmHg, P = 0.002–0.004; 7–8 bpm, P = 0.01–0.04) on the high-carb diet at 14 weeks than on the high-mono or the high-carb diet at 6 weeks. For both diastolic blood pressure and heart rate, there was no difference between the high-carb and high-mono diets at 6 weeks. There was no significant diet effect for systolic blood pressure; however, it was higher (6 mmHg; P = 0.04) on the high-carb diet at 14 weeks than on the high-mono diet at 6 weeks, and the difference was reflected in the confidence intervals of 0.4–10.5 mmHg.

Analysis of the weekly blood pressure collected during outpatient follow-up in phases 1, 2, and 2 extension showed a significant order by diet interaction for systolic (P = 0.03) and diastolic (P = 0.04) blood pressure . Figure 2A shows the weekly mean systolic and diastolic blood pressure in 13 patients who received the high-mono diet for 6 weeks during phase 1 and the high-carb diet for 14 weeks during phases 2 and 2 extension. There was no significant diet effect (P = 0.8) for either systolic or diastolic blood pressure, although they tended to be higher during the high-carb phase than at the end of the high-mono phase. Figure 2B shows the weekly mean systolic and diastolic blood pressure in the eight patients who received the high-carb diet for 6 weeks during phase 1 and the high-mono diet for 14 weeks during phases 2 and 2 extension. There was a significant diet effect for both systolic (P = 0.03) and diastolic (P = 0.03) blood pressure. Systolic and diastolic blood pressure were significantly lower on the high-mono diet during the phase 2 extension than on the high-carb diet during phase 1 (P = 0.009 and P = 0.01, respectively). The results were similar even when the inpatient data were excluded from the analysis.

View larger version (33K): [in this window] [in a new window]   Figure 2— Blood pressure results in patients participating in the phase 2 extension. A: Weekly mean (±SE) systolic (, •) and diastolic (, ) blood pressure in 13 patients who participated in the phase 2 extension and consumed the high-carb diet for 8 additional weeks. B: Weekly mean (±SE) systolic (, •) and diastolic (, ) blood pressure in eight patients who participated in the phase 2 extension and consumed the high-mono diet for 8 additional weeks. , , mean values during outpatient follow-up; •, , mean of the determinants during the last 3 days of each phase in the inpatient centers.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

The 6-week results from our study were not corroborated by the results from the 3-week cross-over study in type 2 diabetic subjects conducted by Rasmussen et al. (4) in which daytime ambulatory blood pressure was higher on a high-carbohydrate diet than on a high—monounsaturated fat diet. A possible reason why that study found a blood pressure response to the diets at 3 weeks compared with our study, in which a small difference was seen only with longer-term consumption of the diets, could be partly due to the fact that their study had a higher difference in the percentage of energy from monounsaturated fat between the two diets (high—monounsaturated fat diet: 30%; high-carbohydrate diet: 10%) than that in the present study (high-mono diet: 25%; high-carb diet: 10%). The smaller difference in monounsaturated fat content in our study may have led to a delayed blood pressure response, suggesting that long-term studies may be necessary to evaluate the blood pressure response to high-carbohydrate and high—monounsaturated fat diets, especially when the difference in monounsaturated fat content of the two diets is at the level shown in our study. It is not clear why Rasmussen et al. (4) did not find a difference in nighttime blood pressure and clinic blood pressure on the two diets.

A number of other studies that also compared high-carbohydrate and high—monounsaturated fat diets, however, did not find a difference in the blood pressure response (6–9). The results from these studies are difficult to compare with the results from our study, however, as most of the studies (6,7,9) were only 21–36 days in duration, whereas for some patients in our study, phases 2 and 2 extension were implemented for a total of 14 weeks. The short duration of the former studies may have been a limiting factor leading to a possible delayed response. Also, in two of the four studies (6,8), the percentage of energy from saturated fat was higher (2–3.2%) and the dietary fiber content was lower (9–18 g) on the high—monounsaturated fat diet compared with the high-carbohydrate diet. These differences could have mitigated any possible blood pressure–lowering effect of monounsaturated fat as diets high in saturated fat or low in fiber have been reported to raise blood pressure (13,14). In our study, the percentage of energy intake from saturated fat was held constant across the two diets (10% of total energy), and dietary fiber intake was kept proportional to the carbohydrate content; thus, a patient on a 2,000-kcal diet would have received 22 g of dietary fiber on the high-mono diet and 30 g on the high-carb diet. Based on a meta-analysis by Streppel et al. (14) in which an average fiber supplementation of 11.5 g/day reduced systolic blood pressure by 1.13 mmHg and diastolic blood pressure by 1.26 mmHg, the differences in blood pressure between the two diets in the present study might have been slightly higher had the fiber content of the high-mono diet been as high as the fiber content of the high-carb diet.

The most plausible mechanism for an increase in blood pressure and heart rate on a high-carbohydrate diet compared with a high—monounsaturated fat diet might be the accentuation of hyperinsulinemia. Data on insulin concentration in the present study that were previously reported (10) showed that compared with the high-mono diet, the high-carb diet increased daylong plasma insulin values by 10% and that the effects persisted for 14 weeks. It has been postulated that hyperinsulinemia enhances sympathetic nervous system activity, which increases heart rate, cardiac output, vascular resistance, and Na⁺ retention and thus blood pressure (15,16).

A possible limitation of the present study is the fact that we did not record 24-h ambulatory blood pressure. According to one study (17), the variability in blood pressure measurements is twice as large for clinic measurements as for ambulatory measurements, although the difference between clinic and average daytime ambulatory blood pressure in this study was not significant. Our variability was probably minimized, however, because the measurements were made under controlled inpatient conditions and because the sample size in our cross-sectional study was large. Nevertheless, future studies need to investigate the long-term effects of these diets using the 24-h ambulatory blood pressure method because of the variability in blood pressure during the day and night and the ability of the method to observe blood pressure behavior during normal daily activities.

It has been suggested that decreases in blood pressure in a trial may be due to a habituation effect (18). Blood pressure decreased slightly on the high-mono extension phase in our study. However, we do not believe this change was due to a habituation effect, given the fact that a significant rise in blood pressure was observed during the high-carb extension phase. Also, the lowering of blood pressure due to habituation reaches a plateau after 1 week (18).

Another possible limitation of this study was that we did not specifically control the intake of minerals linked to blood pressure. According to meta-analyses, potassium supplementation leads to a significant reduction in blood pressure (19); magnesium supplementation leads to a small, nonsignificant decrease in blood pressure (20); and calcium supplementation is inconsistently linked to blood pressure (21). Also, decreasing sodium intake may lead to lower blood pressure (22). Based on the menus for the 2,000-kcal diets in our study, the intake of sodium, potassium, magnesium, and calcium was 345, 574, 90, and 79 mg higher, respectively, on the high-carb diet than on the high-mono diet. The higher sodium content of the high-carb menus is unlikely to have contributed to a higher blood pressure as the total sodium content of the high-carb menus was only 1,546 mg/day; in addition, the menus had a higher potassium content to balance out any possible effect of sodium on blood pressure. The difference in magnesium and calcium content between the two diets is too small to result in any clinically relevant difference in blood pressure (20,21).

In conclusion, over a short period, high-carbohydrate and high—monounsaturated fatty acid diets are not related to blood pressure, but over a longer period (e.g., here 14 weeks), a high-carbohydrate diet may modestly increase blood pressure compared with a high—monounsaturated fat diet.

	Acknowledgments

 
This study was supported in part by a grant from Pfizer (New York, NY); National Institutes of Health Grants M01-RR00633, MO1-RR-00400, M01-RR-00827, M01-RR00070, HL-29252, HL-08506, and DK-38949; and the Medical Research Service of the San Diego (CA) Veterans Affairs Medical Center.

	Footnotes

 
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Received for publication July 11, 2005. Accepted for publication August 8, 2005.

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TOP ABSTRACT INTRODUCTION RESEARCH DESIGN AND METHODS RESULTS CONCLUSIONS References

 

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This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shah, M. Articles by Garg, A. Search for Related Content PubMed PubMed Citation Articles by Shah, M. Articles by Garg, A. Social Bookmarking                What's this?