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Dietary Alterations in Plasma Very Low Density Lipoprotein Levels Modify Renal Excretion of Urates in Hyperuricemic-Hypertriglyceridemic Patients¹

Metabolic Unit, Section of Endocrinology, Regional Hospital of Malaga (J.F.T., F.J.C-S., A.P.), Malaga; and Unit of General Pathology, Section of Rheumatology, Faculty of Medicine, University of Cordoba (G.P.-L., P.S.-G., E.C.), Cordoba, Spain

Address all correspondence and requests for reprints to: Dr. F. J. Tinahones, Ayala, 28–4^a Esc, 6° A, E-29002 Malaga, Spain.

	Abstract

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Hyperuricemic-hyperlipidemic patients exhibit decreased renal excretion of urates relative to purely hyperuricemic patients; also, very low density lipoprotein (VLDL) levels are inversely proportional to the amount of urate excreted. Based on this knowledge, the aim of this study was to alter VLDL levels by dietary manipulation and assess its effect on uric acid levels and renal excretion of uric acid.

Thirty-six men were studied in 2 groups consisting of 20 primary hyperuricemic (group I) and 16 primary hyperuricemic-hypertriglyceridemic patients (group II). The patients were analyzed for apoproteins and lipoproteins, urate levels, and renal excretion of uric acid in a first, basal determination, after 3 weeks of a 1200-Cal diet, and after another 3 weeks of a 2500-Cal diet.

After the 1200-Cal diet, patients in group I exhibited significantly decreased levels of cholesterol (P < 0.05) and apoprotein CIII (P < 0.05). There were significant differences in renal excretion of uric acid (P < 0.05) between the basal and third determinations. Patients in group II exhibited significantly decreased levels of triglycerides (P < 0.01), VLDL cholesterol (P < 0.01), VLDL triglycerides (P < 0.01), and VLDL apoprotein B (P < 0.05) after the 1200-Cal diet; all of these parameters returned to values similar to the basal levels on completion of the 2500-Cal diet. With regard to purine parameters, the low calorie diet led to significantly increased fractional excretion of uric acid (P < 0.01) and uric acid clearance (P < 0.01), both of which decreased significantly to values near basal after the 2500-Cal diet. The results obtained in this study reveal that the decreased levels of triglyceride and VLDL components that arise from a low calorie diet are accompanied by increased renal excretion of urates and that the increase in the amount of this type of lipoprotein particle with an increase in dietary energy offsets the increase in renal excretion of urate.

	Introduction

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HYPERURICEMIA has been associated to obesity (1), hypertriglyceridemia (2), impaired glucose tolerance (3), and hypertension (4). Healthy males with asymptomatic hyperuricemia have also been shown to be relatively hyperinsulinemic (5).

A potential association between the factors related to hyperuricemia and its pathogeny has been postulated. In this respect, we found hyperuricemic-hyperlipidemic patients to exhibit decreased renal excretion of urates relative to purely hyperuricemic patients (6) and that VLDL levels are inversely proportional to the amount of urate excreted (7). Some drugs that lower triglyceride levels have been found to have a uricosuric effect (8, 9).

In this work, we altered VLDL levels through dietary manipulation in hyperuricemic-hypertriglyceridemic patients to evaluate the effects on uric acid levels and renal excretion of urates in a prospective manner. Our preliminary results (10) suggest that the decreased triglyceride levels in hyperuricemic-hypertriglyceridemic patients after a low calorie diet are concomitant with decreased uric acid levels and increased renal excretion of urates, and that this is not the case with hyperuricemic-normolipidemic patients.

	Subjects and Methods

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A total of 36 men were studied in 2 groups consisting of 20 primary hyperuricemic patients (group I) and 16 primary hyperuricemic-hypertriglyceridemic patients (group II). Secondary hyperuricemic and hyperlipidemic patients were excluded from the study after taking a detailed history and carrying out laboratory determinations to rule out diabetes, hypothyroidism, renal or hepatic insufficiency, medication and alcohol use, etc. None of patients had a history of gout or was a smoker.

All patients were subjected to an initial basal analytical determination after 3 days of a low purine diet (11). Individuals with plasma uric acid concentrations above 7 mg/dL were classed as hyperuricemic, and those with plasma triglyceride levels exceeding 200 mg/dL were classed as hypertriglyceridemic.

The second evaluation was performed after 3 weeks of a low calorie diet (1200 Cal/day; 50% carbohydrate, 20% protein, and 30% lipid; 12% monosaturated, 8% saturated, and 10% polyunsaturated fats; foods with a purine content >75 mg/100 g were avoided), and the third was performed after 3 weeks of a 2500-Cal diet with the same composition as the low calorie diet. Three days after the second and third evaluations, patients were again placed on a low purine diet similar to that used before the first determination. Dietary compliance was verified by a weekly questionnaire. The project was approved by Carlos Haya Hospital Ethics and Clinical Investigation Committee, and informed consent was obtained from all participants.

Analytical determinations

All patients were subjected to blood analyses for uric acid, total triglyceride, creatinine, apoprotein AI (by nephelometry), apoprotein B (by nephelometry), apoprotein CII (by radial immunodiffusion), apoprotein CIII (by radial immunodiffusion), VLDL cholesterol, VLDL triglycerides, VLDL apoprotein B, and high density lipoprotein (HDL) cholesterol determinations after 12 h of fasting.

Creatinine clearance and uric acid excretion, clearance, and fractional excretion were determined in 24-h urine samples. Heavy physical exertion during the urine collection period was disallowed.

Lipoprotein separation

The VLDL fraction was separated by ultracentrifugation on a Beckman TL-100 ultracentrifuge (Palo Alto, CA) equipped with a fixed angle rotor at 55,000 rpm and 10 C for 18 h. HDL cholesterol, precipitated with phosphotungstic acid, was determined in the infranatant after the extraction of VLDL.

Statistical analysis

Results are given as the mean and SD. Data were subjected to the Kruskal-Wallis and Duncan tests to identify differences in each group among the three determinations. Statistically significant differences between the two groups were established using the Mann-Whitney test. Ho’s rejection level was always 0.05.

	Results

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The patients in group I were 44 ± 7.8 yr old, and those in group II were 50 ± 10.8 yr old. The body mass indexes for the two groups were 28.9 ± 3.2 and 27.9 ± 3.3 kg/cm², respectively. The differences between these two values were, thus, statistically insignificant.

Table 1 shows the weight and lipid parameter changes observed in groups I and II. The patients in group I lost 4 kg, on the average, as a result of the low calorie diet, and weight was unchanged after the 2500-Cal diet; the weight differences between determinations were statistically insignificant. The 1200-Cal diet significantly decreased cholesterol (P < 0.05) and apoprotein CIII levels (P < 0.05). The patients in group II lost 4.9 kg, on the average, due to the low calorie diet and gained little weight after the 2500-Cal diet. The differences were statistically insignificant. The 1200-Cal diet significantly decreased triglyceride (P < 0.001), VLDL cholesterol (P < 0.01), VLDL triglyceride (P < 0.01), and VLDL apoprotein B (P < 0.05) levels, which returned to values close to the basal levels on completion of the 2500-Cal diet.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The results obtained in this study reveal that the decreased levels of triglyceride and VLDL components that arise from a low calorie diet are accompanied by increased renal excretion of urates and that the increase in the amount of this type of lipoprotein particles with an increase in dietary energy offsets the increase in renal excretion of urate. This is consistent with previously reported findings. In fact, some drugs that diminish triglyceride levels have been found to have a uricosuric effect (8, 9). On the other hand, a positive statistical correlation between triglyceride and uric acid levels (12), and a negative correlation of triglyceride and VLDL levels with renal excretion of urates (7) have been established. However, the marked increase in triglyceride levels that results from Intralipid (Kabi Vitrum, Berkeley, CA) infusion does not raise uric acid levels (2); this contradiction may be the result of the VLDL fraction differing structurally and in apoprotein composition from Intralipid.

Hyperuricemic patients have been reported to exhibit altered apoprotein CIII/CII ratios (7, 13). Apoprotein CII is an activator for lipoprotein lipase (14), the enzyme responsible for the hydrolysis of VLDL triglycerides; on the other hand, apoprotein CIII is an inhibitor for lipoprotein lipase (15). We found no changes in the apoprotein CIII/CII ratio in the three determinations, so a potential variation in the proportions of these two apoproteins in the VLDL fraction could not be responsible for their decreased levels after the low calorie diet.

Hyperuricemia was identified as a component of syndrome X by Reaven et al. (16, 17), who associated hyperinsulinemia with hyperuricemia. Facchini et al. (16) found a positive correlation of insulin resistance with serum uric acid levels and a negative one with renal excretion of urates.

The decreased insulin resistance observed after weight loss in this study may have resulted from the increased renal excretion of urates; however, we believe that this was not the case because 1) the weight and also, presumably, the insulin resistance of hyperuricemic-hyperlipidemic patients hardly changed after the 2500-Cal diet, even though renal excretion of urates decreased; and 2) the purely hyperuricemic patients experienced weight changes similar to those in the hypertriglyceridemic group, but exhibited no substantial change in renal excretion of urates.

However, because no insulin peripheral sensitivity tests were performed, we cannot reliably exclude a potential role of insulin in the results, particularly taking into account that some researchers have found an independent statistical correlation of hyperinsulinemia and triglyceride levels with uric acid (12, 18).

The relationship between the decreased triglyceride and VLDL levels and the increased renal excretion of urates suggests that plasma lipoproteins may play some role in renal management of this acid. Determining which component of the renal management of uric acid is responsible for the decreased excretion in hyperuricemic-hypertriglyceridemic patients requires further research. Uric acid crystals have been reported to bind to apoprotein B and E in synovial fluid (19, 20); if uric acid bound to these plasma apoproteins, both of which are highly abundant in VLDL, renal excretion of urates might be decreased at the expense of diminished filtration of free urate. Confirmation of this hypothesis requires ascertaining the physico-chemical state of urate in plasma.

	Footnotes

 
¹ This work was supported by a grant from the FIS (A310552).

Received July 17, 1996.

Revised December 18, 1996.

Accepted December 30, 1996.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

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