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Human Nutrition and Metabolism

Isolated Soy Protein Consumption Reduces Urinary Albumin Excretion and Improves the Serum Lipid Profile in Men with Type 2 Diabetes Mellitus and Nephropathy^1,2

Division of Nutritional Sciences, University of Illinois at Urbana-Champaign (UIUC), Urbana, IL 61801 and ^* Veterans Affairs Illiana Health Care System, Danville, IL 61832

³To whom correspondence should be addressed. E-mail: jwerdman{at}uiuc.edu.

	ABSTRACT

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Soy protein was shown to exhibit several beneficial effects on renal function in nondiabetic patients with nephropathy, and to improve serum lipids. This study examined the effects of isolated soy protein consumption on urinary albumin excretion, serum lipids, plasma amino acids, and isoflavones in diabetic patients with nephropathy. Male patients (n = 14) with type 2 diabetes and nephropathy were followed in a crossover design for 7 mo. The study comprised two 8-wk intervention periods, placed between a 4-wk lead-in and two 4-wk washout periods. In the 2 intervention periods, 0.5 g/(kg · d) of the dietary protein was provided as either isolated soy protein (ISP) or casein, in random order. Blood and urine samples were collected at the beginning and end of each period. Data were analyzed by multiple linear regression for a repeated-measure design. ISP consumption led to changes of –9.5% in urinary albumin excretion (P < 0.0001), –0.45 in the total-to-HDL-cholesterol ratio (P < 0.05), –0.20 in the LDL-to-HDL cholesterol ratio (P < 0.05), and +4.3% in HDL cholesterol (P = 0.0040). Plasma arginine concentrations, the arginine-to-lysine ratio, and plasma isoflavone concentrations were higher after ISP consumption (P < 0.05). Urinary albumin excretion was negatively correlated with plasma total isoflavones ( = –0.441), daidzein ( = –0.326), and O-desmethylangolesin ( = –0.389) (P < 0.05). The findings indicate that isolated soy protein consumption improves several markers that may be beneficial for type 2 diabetic patients with nephropathy.

KEY WORDS: • men • soy protein • type 2 diabetes • urinary albumin • blood lipids

Type 2 diabetes mellitus is rapidly reaching epidemic proportions in the United States and other countries with Westernized lifestyles. It is now estimated that at least 16 million Americans have diabetes, with 90–95% suffering from type 2 (1,2). According to the Centers for Disease Control, these numbers continue to grow (2).

Diabetes mellitus is associated with several major long-term complications (3), including diabetic nephropathy and coronary heart disease (CHD).⁴ Diabetic patients have higher incidences of these 2 diseases. Also, when they are afflicted with these diseases, the prognosis is generally worse (3). Frequently, when type 2 diabetes is diagnosed, elevated urinary albumin excretion is already present (4). Such elevations indicate morphological and functional anomalies in the kidney (5) and are associated with an increased risk of cardiovascular disease deaths (4,6). In diabetic patients, elevated blood lipid levels are also associated with the risk of CHD, just as they are in the general population (3). Thus, strategies that promote a reduction in urinary albumin excretion and an improvement in lipid profile (i.e., reduced total cholesterol and LDL cholesterol, and increased HDL cholesterol) may help to reduce the risks for both diabetic nephropathy progression and CHD.

Restricting dietary protein intake has long been known to reduce urinary albumin excretion. It is also beneficial for the prevention and treatment of diabetic nephropathy (7,8). Recently, instead of reducing protein intake, some interest has been directed toward manipulating the dietary protein quality, specifically by replacing animal protein with soy protein (9). Soy protein was shown to improve the lipid profile in mildly hypercholesterolemic individuals without diabetes (10,11). It was also shown to reduce urinary albumin excretion and total cholesterol in nondiabetic patients with nephrotic syndrome (12–14). Improvements in kidney function were shown in animal models of polycystic kidney disease (15–19) and in the remnant kidney rat model (20,21). Recent results from our group showed that a high soy protein diet was able to halt the increase in urinary albumin excretion typically seen in a type 2 diabetes mellitus mouse model, the db/db mouse (22,23). Thus, there is a growing body of evidence indicating that soy protein consumption may have beneficial effects for nephropathy and CHD in general.

However, reported studies that focused specifically on diabetic patients with diabetic nephropathy are scarce, and the available results are inconsistent. Jibani et al. (24) and Kontessis et al. (25) found that soy protein consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas Anderson et al. (26) found an increase in urinary protein excretion when soy protein was consumed by type 2 diabetic patients with urinary protein excretion < 1000 mg/d and serum creatinine < 176.8 µmol/L (<2 mg/dL). Recently, Azadbakht et al. (27) found a reduction in urinary urea nitrogen and protein in type 2 diabetics with nephropathy consuming a diet with 35% soy protein. Only a small number of studies have examined the effects of soy protein on blood lipids in type 2 diabetic patients. Anderson et al. (26) found a significant reduction in total cholesterol and triglycerides. Hermansen et al. (28) reported an improvement in blood lipid profile when soy protein was consumed by type 2 diabetic patients without diabetic complications. In the study of Azadbakht et al. (27), the lipid profile also improved during the soy protein consumption period.

The objective of this study was to investigate the effects of isolated soy protein (ISP) consumption in type 2 diabetic patients. In particular, the effects of consuming 0.5 g/(kg · d) of ISP on urinary albumin excretion and the blood lipid profile were determined in patients at early stages of diabetic nephropathy. We hypothesized that ISP consumption compared with casein would decrease urinary albumin excretion, improve the blood lipid profile, alter plasma amino acid concentrations, and increase plasma isoflavone concentrations.

	SUBJECTS AND METHODS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Subjects. Free-living men (n = 34; age range 53–73 y) were recruited at the Danville Veterans Affairs Illiana Health Care System (V.A.I.H.). "Free-living" refers to outpatients who continue their normal daily activities except for changes described in the paper. The primary inclusion criteria were type 2 diabetic patients with diabetic nephropathy (as assessed from the medical chart), 24-h urinary albumin < 2000 mg/24 h, serum creatinine < 1.5 mg/dL (132.6 µmol/L), and a BMI < 36 kg/m². Exclusion criteria included nondiabetic nephropathy, taking angiotensin-converting inhibitors (ACEi) for <8 wk, previous organ transplant, steroid therapy, and any other chronic illness that could either affect markers being measured or limit the individual’s ability to participate in the study. Subjects who failed to consume the study proteins, underwent hospitalizations or had changes in ACEi and lipid-lowering drugs during the study were excluded from data analysis. The study was approved by the Institutional Review Boards at the University of Illinois at Urbana-Champaign (UIUC) and at the Danville V.A.I.H. Informed consent forms were signed by all subjects before starting the study.

The study was performed in three 7-mo cohorts, with cohort 1 taking place between September 1999 and April 2000 (n = 18), cohort 2 between May and December 2000 (n = 8), and cohort 3 between February and August 2001 (n = 10). Cohorts 1, 2, and 3 ended with 10, 5, and 6 subject dropouts, respectively. From these, 17 subjects chose to withdraw from the study. Most withdrew due to work/travel issues because the subjects were studied on an outpatient basis. Because the Danville V.A.I.H. coverage area is wide, extensive travel (>1 h each way) was required for some patients, making it difficult to both recruit and retain patients in the study. Three subjects were dropped from the study due to changes in ACEi and/or lipid-lowering drugs. Two subjects were dropped due to hospitalization from conditions unrelated to the study. Data from the remaining 14 subjects were used for statistical analysis. All patients had been receiving ACEi for >8 wk at the start of the study, and 4 had been taking lipid-lowering drugs [e.g., 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors] for >12 wk. All patients were taking antihypertensive drugs and 8 were receiving insulin in addition to oral antidiabetic drugs. All patients had type 2 diabetes for >5 y, with a mean duration of 14 y.

    Diet and design. The study had a crossover design, with each subject serving as his own control. Subjects were followed for 7 mo, during which 2 experimental diets with 0.5 g/(kg · d) of either ISP or casein were consumed for 8 wk each in random order. These two 8-wk intervention periods were placed between a 4-wk lead-in and two 4-wk washout periods.

During the lead-in and washout periods, a basal diet with 1 g/(kg · d) of protein from nonsoy sources, <30% of energy as fat, <10% as saturated fat, and <300 mg/d of cholesterol was prescribed by a registered dietitian (RD), according to individual needs and preferences. The subjects were counseled on their own nutritional needs, and were asked to keep a consistent activity level throughout the study.

The subjects were randomly assigned in a sequential manner using a Latin-square design to determine the order of receiving the 2 experimental diets during the intervention periods. The experimental diets were based on the basal diets, but the patients were instructed to replace 0.5 g/(kg · d) of the total dietary protein intake with either ISP (HP20 Soy 1.2, Protein Technologies International) with 2.0 mg isoflavones aglycone units/g protein, or casein (milk protein; HP20 TMP Placebo, Protein Technologies International). The ISP and casein were provided in the form of protein powders with a light vanilla flavor, which could be incorporated easily into several dishes or drinks, as instructed by the RD.

The subjects visited the RD every 2 wk; at these visits, compliance and body weight were monitored, 3-d dietary records were collected, and the subjects received soy protein or casein powder for the next 2 wk. At wk –4, 0, 8, 12, 20, and 24 (wk 0 denotes the start of the first intervention), blood and urine were collected and each subject also visited a physician.

Mean daily nutrient intake was analyzed using a computerized nutrient database (NUTRITIONIST V, version 2.1.1, 1999, First DataBank), as soon as the dietary records were received every 2 wk. Statistical analysis was performed on 7 food records chosen at regular intervals during the course of the study (with 1 food record from the lead-in, 2 from each intervention and 2 from each washout period). Compliance with the protein powders was monitored by weighing the leftover powder from the previous 2 wk.

    Blood and urine analyses. Blood samples (50 mL) were collected at the Danville V.A.I.H. in the morning on 2 consecutive days after a 12-h fast, at 6 time points (wk –4, 0, 8, 12, 20, and 24). Results from the 2 consecutive days were averaged before statistical analysis. Plasma and serum were obtained after centrifugation at 1500 x g for 30 min at 4°C. A portion of the plasma and serum was analyzed immediately at the Danville V.A.I.H. as indicated below. The remainder was refrigerated and transported to the University (UIUC), where aliquots of plasma and serum were frozen at –70°C until analysis, which was performed at the end of each cohort. At the same time points of blood collection, a total of six 24-h urine samples were obtained, which were refrigerated until processed at UIUC. The subjects were instructed to obtain a full 24-h collection. The collection was repeated if not complete.

Plasma or serum samples at all time points were analyzed for glucose, total and A1c glycated hemoglobin (TGHb and GHb A1c, respectively), creatinine (Cr), urea nitrogen, albumin, total protein, electrolytes (sodium, potassium, and phosphorus), total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglycerides (TG). In addition, plasma isoflavones (at wk 0, 8, 12, and 20) and plasma amino acids (at wk 8 and 20) were measured. Urine samples (24-h) were analyzed for volume, Cr, and albumin. Cr clearance was calculated, and urinary albumin excretion was assessed by the urinary albumin-to-creatinine ratio (UAC) in mg/g. Plasma glucose, and serum urea nitrogen, albumin, total protein, sodium, potassium, phosphorus, TC, HDL cholesterol, and TG were analyzed at the Danville V.A.I.H. in a Monarch auto-analyzer (Instrumentation Laboratory; CV < 4%) using reagents from the Instrumentation Laboratory. HDL cholesterol was determined using a precipitation method with reagents from Data Medical Associates (Cat. No. 1335–125). Blood TGHb and GHb A1c were determined at the Danville V.A.I.H. by the GHb affinity column method (29) in a ColumnMate300 (Helena Laboratories) with a CV < 6%. Serum and urinary Cr were analyzed in a Hitachi 911 system at the Pathology Laboratory, Department of Veterinary Medicine, UIUC (CV < 5%) using Roche Diagnostics kits.

LDL cholesterol was analyzed using a homogeneous enzymatic LDL cholesterol assay, the LDL Direct Select cholesterol reagent (Equal Diagnostics) with an interassay CV < 10%. LDL cholesterol concentrations were determined from a linear fit to the measurements of the assay standards. Urinary albumin was analyzed by ELISA using a commercial kit (ORGenTec, KMI diagnostics) with specific antibodies for human albumin. Albumin concentrations were obtained by nonlinear regression with a 4-parameter logistic equation that approximated the shape of the standard curve. The intra-assay CV was <5%.

Plasma amino acid concentrations were determined by ion-exchange liquid chromatography in a Beckman 6300 automated amino acid analyzer (Beckman Coulter) using a 10-cm column (Beckman Coulter). Plasma samples were first deproteinized using sulfosalicylic acid. The supernatant was then diluted with lithium citrate at pH 2.2. The interassay CV was <3%.

Plasma isoflavone concentrations were measured from the first-day plasma collected at the 4 time points before and after each intervention period. The isoflavones genistein, daidzein, dihydrodaidzein, O-desmethylangolensin (O-DMA), and equol were measured by HPLC coulometric array detection (model 5600 CoulArray 8-channel detector; Ralston Analytic Laboratories, Ralston Purina), as described by Coward et al. (30). Total isoflavone concentrations were determined by summing the concentrations of the individual isoflavones.

    Other measurements. Body weight was monitored bimonthly (Detecto Physician Dual Reading Scale) and BMI was calculated. The daily activity level was assessed with 3-d activity records, which were completed monthly. An activity score was calculated from the information provided on the activity records, as described by Bouchard et al. (31). Blood pressure was measured every 2 wk.

    Statistics. For most urine and blood measurements (unless specified below), the effects of ISP vs. casein were analyzed by multiple linear regression for a repeated-measure design (32). The outcome variable was the change from baseline for each subject; baseline was the value before each intervention, and diet was dummy-coded as the main factor. The baseline values of the outcome variables were included in the model as a covariate, coded as the deviation from the baseline mean. The interaction between diet and covariate was analyzed to determine the effect of baseline values on treatment effect. The subjects were effects-coded according to subject variable coding. The intercept term of the regression model represents the change from baseline in the casein group (33) at the baseline mean. The main factor and covariate were examined only if the multiple R² for the model was significant (P < 0.05).

Correlations of plasma isoflavones with lipids and UAC were analyzed by Spearman rank-order correlation. Paired t test was used to compare fasting plasma amino acid concentrations and ratios, and the changes in isoflavones concentrations. Nutrient intake, physical activity, and BMI during the 5 study periods (1 lead-in, 2 intervention, and 2 washout periods) were compared by multiple linear regression for a repeated-measure design (32). The outcome variable was the mean value during each period, and the 5 study periods served as a 5-level effects-coded main factor. Subjects were effects-coded according to subject variable coding. The main factor was examined only if the multiple R² for the model was significant (P < 0.05). If a significant effect of study period was detected, differences between study periods were analyzed further by least significant difference (LSD). All statistical analyses were conducted with an level of 0.05 using the Statistical Analysis System (SAS version 8.01, SAS Institute).

	RESULTS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
    Dietary intake, physical activity, BMI, and blood pressure. Consumption of the study protein was well accepted by most of the subjects. Compliance, as measured from the leftover protein powder, was 99 and 95.5% for ISP and casein, respectively. However, 5 of the 17 subjects who dropped out described symptoms of possible intestinal intolerance to the protein powders (2 subjects to casein, and 3 to ISP), such as bloating and changes in intestinal transit time.

Energy and macronutrient intake were similar during the 2 intervention periods, and during the 2 washout periods (Table 1). However, there were some differences among the lead-in, intervention, and washout periods, despite diet counseling. These differences occurred because the subjects added the protein powders during the intervention periods instead of substituting other proteins as instructed. Thus, overall energy and protein intakes were higher and the percentage of fat intake was lower during the intervention periods. The 5 study periods did not differ otherwise in intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, fiber, and cholesterol, and percentage intake of polyunsaturated fat.

View larger version (29K): [in this window] [in a new window]   FIGURE 1 Protein intake in men with type 2 diabetes and nephropathy before, after, and during periods of consuming soy protein or casein. Values are means ± pooled SEM, n = 14. Bars with different markings (Greek symbols for total protein, lowercase letters for animal protein including casein, uppercase letters for vegetable protein including soy protein) differ, P < 0.0001.

    Urine. UAC was reduced by ISP consumption (–20.3 mg/g, P < 0.0001), but was increased by casein consumption (+16.29 mg/g, P = 0.0020). The effect of dietary treatment was dependent on the baseline UAC level (P < 0.0001 for the interaction "Dietx Baseline mean"), and the difference between dietary treatments was larger in men with higher initial UAC. Cr clearance did not change (Table 2andFig. 2).

View larger version (15K): [in this window] [in a new window]   FIGURE 2 Changes in the urinary albumin-to-creatinine ratio (UAC) in men with type 2 diabetes and nephropathy before, after, and during periods of consuming soy protein or casein. Values are means ± pooled SEM, n = 14. *Different from baseline, P < 0.0020; **different from casein, P < 0.0001. Significant interaction "Dietx Baseline mean," P < 0.0001.

Plasma isoflavone concentrations were significantly higher after soy than after casein consumption (Table 4). The only exception was equol, for which the difference was not significant (P > 0.05). When correlations between outcomes and plasma isoflavones were determined, only those with the change in UAC were significant. The change in UAC was negatively correlated with plasma total isoflavones ( = –0.441, P = 0.012), daidzein ( = –0.326, P = 0.045), and O-DMA ( = –0.389, P = 0.020). The remaining correlations analyzed were not significant. The changes in all the other blood outcomes were not significant.

	DISCUSSION

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

Consumption of 0.5 g/(kg · d) of ISP instead of casein reduced urinary albumin excretion 9.5% in type 2 diabetic patients. This reduction was dependent on the baseline values, with higher baseline excreters having larger reductions. In our study, the actual total protein intake was higher during both intervention periods [1.4 g/(kg · d)] than during the lead-in or washout period [0.9 g/(kg · d)]. This was because the subjects added the soy and casein powders to the diet, rather than replacing an equivalent amount of dietary protein as originally intended. Therefore, we cannot exclude that the increased protein intake during the intervention periods did not influence the significant effect of the ISP. Nevertheless, this discrepancy did not affect the experimental comparisons between ISP and casein because there were no differences in total protein intake between the 2 intervention periods. This may be further supported by recent results from our group in an animal model of type 2 diabetes (22,23). In that study, effects of soy protein compared with casein were significant only at the higher protein intake (20% of energy).

It should be noted that despite the lower total protein intake during the lead-in period, urinary albumin excretion did not decrease during that period (wk –4 vs. wk 0). The lack of response could have been due to the short duration of the lead-in period. Another important observation was that UAC continued to decrease during the washout after ISP consumption. These findings suggest that the effects of ISP on UAC may linger, especially when accompanied by a reduction in protein intake. In future studies, it may be useful to have longer washout periods.

The present findings on urinary albumin excretion were independent of metabolic control because both total and A1c glycated hemoglobin did not differ between the 2 intervention periods. The changes in urinary albumin excretion were in addition to the effects of ACEi because all of the patients had been taking ACEi for >8 wk.

Other studies indicated that the consumption of vegetable protein, including soy protein, reduces urinary albumin excretion in diabetic patients. For example, Jibani et al. (24) found a significant reduction in fractional albumin excretion in type 1 diabetic patients after a predominantly vegetarian diet was consumed for 8 wk. However, the role of the vegetable protein could not be distinguished from the role of reduced protein intake because the vegetable protein diet was also lower in protein. Kontessis et al. (25) found a significant reduction in fractional clearance of albumin after an exclusively vegetable protein diet was consumed by type 1 diabetic patients for 4 wk. The authors also found a reduced glomerular filtration rate and reduced renal plasma flow after the vegetable protein diet. Total protein intakes were similar during the 2 diets [1 g/(kg · d)]. Recently, Azadbakht et al. (27) reported reductions in urinary urea nitrogen and protein in type 2 diabetics with nephropathy after consumption of a diet with 0.8 g/kg protein with 35% soy protein.

However, some inconsistencies exist in the literature. In contrast to the above reports, some studies showed a lack of improvement in urinary protein excretion after vegetable or soy protein consumption. For example, Anderson et al. (26) found an increase in urinary protein excretion in type 2 diabetics when 50% of the dietary protein [0.5 g/(kg · d)] was provided in the form of soy protein. They suggested that the diabetes type might explain the unexpected results. Other factors that may have affected their findings included the lack of a double-blind trial, the lack of monitoring on the effective compliance with the meal plans, and the nutrient intake, as well as the degree of kidney involvement, which was slightly more severe than in the present study, as assessed by serum Cr concentrations.

More recently, Wheeler et al. (34) reported no clear advantage of diets containing only plant protein (62% of which was from soy sources) vs. mixed diets (40% vegetable protein) in individuals with type 2 diabetes and microalbuminuria. There are key differences between the population studied by Wheeler et al. and the current study. The present study included both micro- and macroalbuminuric patients, whereas the study of Wheeler et al. (34) included only microalbuminuric patients. This is an important distinction because we found that the effects of ISP on urinary albumin excretion were dependent on the initial excretion of albumin. The results of Azadbakht et al. (27) further support the relevance of initial albumin excretion. In that study, all patients were macroalbuminuric, and significant reductions in urinary protein were found. Unfortunately, the number of patients in our study does not allow for subgroup analysis. Further research must be conducted to better understand the importance of the initial urinary albumin excretion level. Another key difference is the source of soy protein (and isoflavone content) used in different studies. In the present study, the source of soy protein was ISP with a high level of isoflavones. In the study of Wheeler et al. (34), the isoflavone composition, although not reported, was expected to be low considering the sources of soy protein used (tofu, textured soy protein, and soy milk). The source of soy protein or isoflavone content was not reported in the study of Azadbakht et al. (27).

The present study also investigated the effects of ISP consumption on blood lipids. We did not find a significant reduction in total or LDL cholesterol after ISP consumption. This may be expected because several studies have shown that ISP significantly reduces cholesterol concentrations only in individuals with initially above-normal concentrations (35). In the present study, the baseline total and LDL cholesterol concentrations were in the desirable and optimal categories accordingly to the National Cholesterol Education Program (36). Additionally, several of these patients were already taking lipid-lowering drugs (e.g., HMG-CoA reductase inhibitors) which might have interfered with the effects of ISP on total and LDL cholesterol. Our results are also in agreement with those of Wheeler et al. (34), in which patients with normal cholesterol concentration were studied and no significant improvements were found in TC or LDL cholesterol. Although 2 other studies reported significant reductions in total and LDL cholesterol in type 2 diabetics with nephropathy consuming soy protein (26,27), the population in both studies had borderline-normal cholesterol concentrations.

Although we did not find a significant effect of soy on total or LDL cholesterol, there was an overall improvement in the lipid profile. A significant increase in HDL cholesterol (4.3%) and significant reductions in the total-to-HDL cholesterol ratio (–0.45) and in the LDL-to-HDL cholesterol ratio (–0.20) were found after ISP consumption. Neither Wheeler et al. (34) nor Azadbakht et al. (27) found a significant increase in HDL cholesterol in their studies. Nevertheless, a trend for increased HDL cholesterol was present in both cases. Only Azadbakht et al. reported data on cholesterol ratios and no effect was seen.

In the present study, we found a significantly higher fasting plasma concentration of arginine and a higher arginine-to-lysine ratio after ISP consumption. These findings, although novel, are to be expected because ISP has more arginine and less lysine than casein (37). In fact, the ratio between these 2 amino acids has been implicated in some health benefits of soy protein (37,38). The importance of the current findings is that differences in arginine concentration and the arginine-to-lysine ratio were found even after a 12-h fast. This indicates that long-term soy consumption can lead to sustained increases in the plasma arginine concentration and the arginine-to-lysine ratio.

ISP contains isoflavones and we found an increase in the various plasma isoflavone concentrations after soy consumption, as would be expected. The significant negative correlations between urinary albumin excretion and plasma concentrations of several isoflavones (total, daidzein, and O-DMA) suggest a potential role for these constituents of ISP in kidney function. This role may be related to their estrogenic activity because estrogens have been implicated in the apparently slower progression of kidney disease in women, compared with men (39).

In conclusion, our results indicate that ISP consumption, in contrast to casein, in type 2 diabetic patients with nephropathy can positively influence several risk factors for CHD and nephropathy progression. The effects of the isoflavone contents and the amino acid composition of soy protein, particularly the arginine-to-lysine ratio, warrant further investigation because they may be the components involved in the effects of soy protein products. These findings are important for type 2 diabetics because these patients are more frequently and more severely affected by both diabetic nephropathy and CHD.

	ACKNOWLEDGMENTS

 
We thank Kendra Budelier, Sandra Hannum, Meg Lindstrom, and Julie Kolodick for their technical assistance and Ruth Thomas for organizational assistance.

	FOOTNOTES

 
¹ Presented in part at the Fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease, November 2001, San Diego, CA [Teixeira, S. R., Tappenden, K., Marshall, W., Carson, L., Ringenberg, M. & Erdman, J. W., Jr. (2002) Effects of soy protein on diabetic nephropathy and blood lipids in type 2 diabetes mellitus. J. Nutr. 132: 584S–585S].

² Supported by Protein Technologies International and the Illinois Council for Agricultural Research (C-FAR). S.R.T. was supported by the Fulbright Program, fellowship 15965032 and the Fundação para a Ciência e a Tecnologia (FCT), Portugal.

⁴ Abbreviations used: ACEi, angiotensin-converting enzyme inhibitors; CHD, coronary heart disease; Cr clearance, creatinine clearance; GhbA1c, A1c glycated hemoglobin; HMG, 3-hydroxy-3-methyl-glutaryl; ISP, isolated soy protein; O-DMA, O-desmethylangolensin; RD, registered dietitian; TC, total cholesterol; TG, triglycerides; TGHb, total glycated hemoglobin; UAC, urinary albumin-to-creatinine ratio.

Manuscript received 3 November 2003. Initial review completed 2 January 2004. Revision accepted 4 May 2004.

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TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

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