Black Soy Peptide Supplementation Improves Glucose Control in Subjects with Prediabetes and Newly Diagnosed Type 2 Diabetes Mellitus

Abstract

The present study aimed to determine the effect of black soy peptide supplementation on glucose control in subjects with prediabetes (impaired fasting glucose or impaired glucose tolerance) and newly diagnosed type 2 diabetes mellitus (DM). In this double-blind, placebo-controlled study, subjects with prediabetes and type 2 DM were randomly assigned to the placebo control group or the black soy peptide intervention group. We determined fasting serum concentrations of glucose, hemoglobin A1c, insulin, and free fatty acids, performed a 2-hour postload glucose (2-hour PG) test, and compared serum lipid profiles before and after the 12-week supplementation. In particular, subjects with fasting glucose ≥110 mg/dL who consumed black soy peptides tended to have lower fasting glucose levels (two-tailed test, P = .098; one-tailed test, P = .049) and had a significant reduction in 2-hour PG level (two-tailed P = .012, one-tailed P = .006), compared with baseline levels. The changes in 2-hour PG levels were also statistically significant in the intervention group (-41.25 ± 13.67 mg/dL) compared with the placebo group (12.42 ± 9.80 mg/dL; two-tailed P = .015, one-tailed P = .008). In contrast, hemoglobin A1c levels were not significantly improved by the dietary intervention. In conclusion, black soy peptide supplementation may be beneficial for controlling fasting blood glucose levels and 2-hour PG levels.

Introduction

A ccording to the 2007 National Health and Nutrition Examination Survey for Koreans, the prevalences of diabetes and impaired fasting glucose were 9.7% and 16.1%, respectively, in Korean adults (≥30 years old).¹ Diabetes is a common endocrine disorder that has become a worldwide health problem. It is characterized by chronic hyperglycemia with disturbances of macronutrient metabolism resulting from defects in insulin secretion, insulin action, or both. Chronic hyperglycemia causes diabetes-related complications such as heart disease, retinopathy, kidney disease, and neuropathy.² Diabetes is diagnosed when the fasting plasma glucose concentration is consistently ≥126 mg/dL or when the plasma glucose concentration is consistently ≥200 mg/dL 2 hours after a 75-g glucose load (2-hour postload glucose [2-hour PG] test). Impaired glucose regulation is associated with high rates of cardiovascular disease and mortality.^3,4

It has been reported that foods or diets that produce a low glycemic response are associated with less insulin resistance and lower risk of type 2 diabetes⁵ and cardiovascular disease.⁶ Among these foods, black soybean is a traditional component of Asian medicine used to treat conditions including diabetes, hypertension, and poor blood circulation.⁷ Diets rich in soy protein and soy peptides have been reported to be beneficial in weight loss, improved insulin resistance and endothelial cell function, and reduced blood pressure and blood lipids.^8

–11 Soy foods have a low glycemic index, suggesting that these soy-rich diets can improve blood glucose and insulin levels.¹² However, few studies have evaluated the effect of black soy peptide supplement on glucose control in humans. Therefore, we determined the effects of black soy peptide supplement on glucose control in Koreans with prediabetes and newly diagnosed type 2 diabetes mellitus (DM).

Subjects and Methods

Subjects

Subjects with prediabetes (impaired fasting glucose or impaired glucose tolerance) and newly diagnosed type 2 DM not requiring medication were recruited from the National Health Insurance Corporation Ilsan Hospital in Goyang, Kyungki Province, Republic of Korea and CHA General Hospital in Seoul, Republic of Korea. Exclusion criteria included (1) history of diabetes, (2) abnormal liver or renal function, (3) history of cardiovascular disease or cancer, (4) pregnancy, breast feeding, or intending to become pregnant during the time of study, and (5) thyroid or pituitary disease. Impaired fasting glucose was defined as fasting glucose between 100 and 125 mg/dL, and impaired glucose tolerance was defined as 2-hour PG levels of 140–199 mg/dL. Newly diagnosed type 2 DM was defined as fasting glucose ≥126 mg/dL or 2-hour PG level ≥200 mg/dL and individuals who had never been diagnosed for DM. Written informed consent was obtained from all subjects, and the protocol was approved by the Ethics Committee of Yonsei University and the Institutional Review Board of the National Health Insurance Corporation Ilsan Hospital. Seventy-five subjects (18–69 years old) met the study criteria, and those who consented to participate in the trial were included in this study (n = 55). Study participants were randomly assigned to the placebo group or the intervention group. Subjects in the intervention group received three pouches containing black soy peptides (4.5 g of supplement/day for 12 weeks). The former group received a placebo that had a similar appearance to the black soy tablet. The black soy peptide supplement and placebo were both provided by Nongshim Co., Ltd. (Dongjak-Gu, Seoul).

Anthropometric parameters, blood pressure measurements, and blood collection

Body weight and height were measured in the morning with the subjects unclothed and without shoes. Body mass index was calculated as body weight (in kg) divided by height (in square meters) (kg/m²). Waist circumference was measured with a paper measuring tape horizontally at the umbilicus in the standing position after normal expiration. Body composition was determined by a foot-to-foot bioelectrical impedance analyzer while the individual was standing erect with bare feet on the analyzer footpads (Tanita, Tokyo, Japan) to obtain lean body mass (kg), fat mass (kg), and body fat (%). Blood pressure was measured using the left arm of the seated patient with an automatic blood pressure monitor (TM-2654, A&D, Tokyo) after a 10-minute rest. The mean of two measurements was recorded for each subject. Venous blood specimens were collected in EDTA-treated and plain tubes after a 12-hour fast. The tubes were placed on ice until they arrived at the laboratory (within 1–3 hours) and were stored at −70°C until analysis.

Glucose, insulin, and free fatty acid concentrations

Fasting glucose was determined by the glucose oxidase method using a Beckman glucose analyzer (Beckman Instruments, Irvine, CA, USA). Insulin was determined by radioimmunoassay with commercial kits from Immuno-Nuclear Corp. (Stillwater, MN, USA). Free fatty acids were analyzed with a Hitachi model 7150 autoanalyzer (Hitachi Ltd., Tokyo).

2-hour PG test

Subjects drank a 75-g glucose solution after an overnight fast. Venous blood specimens were collected before and 120 minutes after glucose ingestion. Glucose was determined by the glucose oxidase method using the Beckman glucose analyzer.

Serum lipid profile and apolipoproteins A-I and B

Fasting serum concentrations of total cholesterol and triglyceride were measured using commercially available kits with the Hitachi model 7150 autoanalyzer. High-density lipoprotein (HDL) cholesterol was measured from the supernatant by enzymatic methods. Low-density lipoprotein (LDL) cholesterol was estimated indirectly with serum triglyceride levels <400 mg/dL using the Friedewald formula. In subjects with serum triglyceride concentrations ≥400 mg/dL, LDL cholesterol was determined directly by an enzymatic method on the Hitachi model 7150 autoanalyzer. Serum apolipoproteins A-I and B were determined by turbidimetry at 340 nm using a specific antiserum (Roche, Basel, Switzerland).

Assessment of food intake and physical activity

Usual food intake was assessed by a 24-hour recall method; a semiquantitative food frequency questionnaire was used to confirm that the data collected by the 24-hour recall method were representative of the usual dietary pattern.¹³ Nutrient intake data were calculated as mean values from the database referenced above. Total energy expenditure (kcal/day) was calculated from the basal metabolic rate, 24-hour physical activity,¹⁴ and the food-specific dynamic action. The basal metabolic rate for each subject was calculated with the Harris-Benedict equation.¹⁵

Statistical analyses

Statistical analyses were performed with the Statistical Package for the Social Sciences version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Each variable was examined for normal distribution, and significantly skewed variables underwent log transformation. For descriptive purposes, mean values of untransformed and unadjusted variables are presented. Baseline characteristics and comparisons between the intervention and control groups were evaluated by Student's t test for continuous variables. A paired t test was used to evaluate the effects of soy peptide or placebo within each group before and after the intervention (in groups of subjects numbering <20, a nonparametric test was used). Only results from the participants who completed the intervention program were analyzed (n = 42). Results are expressed as mean ± SEM values. A P value < .05 was considered statistically significant (we present two-tailed P value/one-tailed P value).

Results

Baseline characteristics and dietary intake change of study participants

Twenty-one of 28 participants (75%) assigned to the soy peptide supplement group and 21 of 27 (78%) of those assigned to the control group completed the intervention and underwent blood analysis at their 12-week visit.

General baseline characteristics were similar between the two groups (Table 1). No significant differences in age, initial weight, body mass index, weight-hip ratio, lean body mass, systolic blood pressure, or diastolic blood pressure were observed between the two groups before or after the intervention. Table 2 presents dietary nutrient intake at baseline and after the 12-week intervention. Total calorie intake, total energy expenditure, and dietary macronutrient intake did not differ significantly between the groups (P > .05).

Table 1.

Characteristics of Study Participants

	Black soy peptides (n = 21)		Placebo (n = 21)
	Baseline	Week 12	Baseline	Week 12
Age (years)	56.8 ± 1.53		57.6 ± 2.01
Height (cm)	161.2 ± 1.58		162.5 ± 2.09
Weight (kg)	62.6 ± 1.47	62.4 ± 1.56	65.8 ± 1.95	65.8 ± 2.04
BMI (kg/m²)	24.1 ± 0.50	24.0 ± 0.53	24.8 ± 0.38	24.8 ± 0.42
WHR	0.91 ± 0.01	0.91 ± 0.01	0.91 ± 0.01	0.91 ± 0.01
LBM (kg)^a	44.9 ± 1.68	45.3 ± 1.82	46.5 ± 2.02	45.8 ± 1.98
Fat (%)	28.5 ± 1.79	27.7 ± 1.73	29.6 ± 1.80	30.8 ± 1.45
SBP (mm Hg)	125.1 ± 3.22	128.2 ± 2.61	126.7 ± 2.93	124.2 ± 2.91
DBP (mm Hg)	73.6 ± 2.36	75.1 ± 1.93	74.5 ± 2.12	74.3 ± 2.07

Data are mean ± SEM values.

Analyzed after log transformation.

BMI, body mass index; DBP, diastolic blood pressure; LBM, lean body mass; SBP, systolic blood pressure; WHR, weight-hip ratio.

Table 2.

Daily Dietary Nutrient Intake at Baseline and After the 12-Week Intervention

	Black soy peptides (n = 21)		Placebo (n = 21)
	Baseline	Week 12	Baseline	Week 12
TEE (kcal/day)	2,020 ± 59.56	2,028 ± 60.26	2,043 ± 65.67	2,046 ± 66.41
Estimated daily nutrient intake
TEI (kcal/day)	2,094 ± 56.65	2,099 ± 57.52	2,168 ± 67.06	2,175 ± 68.55
CHO (%)	61.6 ± 0.18	61.6 ± 0.19	61.6 ± 0.15	61.7 ± 0.17
Protein (%)	16.8 ± 0.24	16.9 ± 0.21	16.7 ± 0.16	16.7 ± 0.18
Fat (%)	21.6 ± 0.21	21.4 ± 0.16	21.8 ± 0.20	21.8 ± 0.21
Cholesterol (mg/day)	204.6 ± 26.85	180.6 ± 14.32	270.0 ± 41.42	237.4 ± 16.12

Data are mean ± SEM values.

CHO, carbohydrate; TEE, total energy expenditure; TEI, total energy intake.

Levels of glucose and related biomarkers

Table 3 presents levels of glucose and related markers after fasting and after the 2-hour PG test. The intervention group demonstrated somewhat lower fasting glucose levels (baseline, 121.62 ± 2.96 mg/dL; after soy peptide supplementation, 117.95 ± 4.06 mg/dL; two-tailed P = .166, one-tailed P = .083) and 2-hour PG levels (baseline, 219.71 ± 18.66 mg/dL; after soy peptides, 200.48 ± 15.03 mg/dL; two-tailed P = .194, one-tailed P = .097) after the 12-week intervention, although this difference was not significant. In addition, free fatty acids were elevated after the 12-week dietary intervention (two-tailed P = .126, one-tailed P = .063). We also observed the changes in the above variables in subjects with fasting glucose ≥110 mg/dL. At baseline, black soy peptide supplementation was associated with a tendency of decreased fasting glucose levels (-4.88 ± 2.79 mg/dL; two-tailed P = .098, one-tailed P = .049) and a significant reduction in 2-hour PG levels (baseline, 243.13 ± 20.44 mg/dL; after soy peptides, 201.88 ± 17.45 mg/dL; two-tailed P = .012, one-tailed P = .006) (Table 4). Changes in 2-hour PG levels were also statistically significant in the intervention group (-41.25 ± 13.67 mg/dL) compared with the placebo group (12.42 ± 9.80 mg/dL; two-tailed P = .015, one-tailed P = .008) in subjects with fasting glucose ≥110 mg/dL at baseline. In contrast, no significant differences in hemoglobin A1c, insulin, and free fatty acid levels were observed.

Table 3.

Glucose-Related Biomarkers at Baseline and After the 12-Week Intervention

	Black soy peptides (n = 21)		Placebo (n = 21)
	Baseline	Week 12	Baseline	Week 12
Fasting levels
Glucose (mg/dL)	121.6 ± 2.96	117.95 ± 4.06	115.38 ± 3.03	114.38 ± 3.61
HbA1c (%)^a	6.70 ± 0.14	6.65 ± 0.14	6.42 ± 0.13	6.45 ± 0.14
Insulin (μIU/dL)^a	11.9 ± 1.63	17.2 ± 5.89	10.57 ± 0.61	11.15 ± 0.91
FFA (μEq/L)	429.8 ± 41.56	503.7 ± 45.25	515.3 ± 39.98	516.2 ± 42.42
2-hour OGTT levels
Glucose (mg/dL)	219.7 ± 18.66	200.5 ± 15.03	182.6 ± 13.30	185.4 ± 14.65

Data are mean ± SEM values.

Analyzed after log transformation.

FFA, free fatty acid; HbA1c, hemoglobin A1c; OGTT, oral glucose tolerance test.

Table 4.

Glucose-Related Biomarkers in Subjects with Fasting Glucose ≥110 mg/dL

	Black soy peptides (n = 16)		Placebo (n = 12)
	Baseline	Week 12	Baseline	Week 12
Fasting levels
Glucose (mg/dL)	126.6 ± 2.92	121.7 ± 4.68^§	124.7 ± 3.15	124.5 ± 3.85
HbA1c (%)^a	6.83 ± 0.17	6.78 ± 0.16	6.77 ± 0.11	6.78 ± 0.14
Insulin (μIU/dL)^a	12.3 ± 1.57	19.3 ± 7.68	9.73 ± 0.82	10.9 ± 0.92
FFA (μEq/L)	465.4 ± 42.29	530.8 ± 51.88	515.5 ± 52.74	549.4 ± 44.45
2-hour OGTT levels
Glucose (mg/dL)	243.1 ± 20.44	201.9 ± 17.45^*	204.5 ± 13.21	216.9 ± 17.18

Data are mean ± SEM values.

Analyzed after log transformation.

P < .1, *P < .05 compared with baseline.

Lipid profiles

Subjects receiving black soy peptides tended to have lower apolipoprotein B levels (two-tailed P = .054, one-tailed P = .027) and a tendency to have higher LDL cholesterol (two-tailed P = .055, one-tailed P = .028) (Table 5). Total cholesterol was also higher in the intervention group, but this was not statistically significant (two-tailed P = .160, one-tailed P = .080). No significant differences were observed for the other variables. Among subjects with fasting glucose ≥110 mg/dL, black soy peptide supplementation was associated with a tendency to have lower apolipoprotein B levels (two-tailed P = .055, one-tailed P = .028; data not shown).

Table 5.

Serum Lipid Profiles at Baseline and After the 12-Week Intervention

	Black soy peptides (n = 21)		Placebo (n = 21)
	Baseline	Week 12	Baseline	Week 12
TG (mg/dL)^a	128.1 ± 17.77	126.6 ± 19.00	128.1 ± 10.28	129.1 ± 14.68
TC (mg/dL)	186.5 ± 6.93	193.3 ± 6.38	190.8 ± 6.51	191.5 ± 7.22
HDL-C (mg/dL)	46.5 ± 2.81	44.9 ± 2.11	45.6 ± 1.92	45.8 ± 1.91
LDL-C (mg/dL)	114.4 ± 5.66	123.1 ± 5.21^§	119.6 ± 6.86	119.9 ± 6.81
Apo A-I (mg/dL)	145.7 ± 5.72	139.7 ± 4.61	152.5 ± 4.31	147.3 ± 4.63
Apo B (mg/dL)	86.1 ± 4.03	80.9 ± 4.62^§	89.7 ± 4.16	87.1 ± 5.96

Data are mean ± SEM values.

Analyzed after log transformation.

P < .1 compared with baseline.

Apo A-I, apolipoprotein A-I; Apo B, apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride.

Discussion

The purpose of the present study was to determine the effects of black soy peptide supplementation on glucose control in Koreans with prediabetes and newly diagnosed type 2 DM. We found that black soy peptide supplementation may reduce fasting glucose levels and 2-hour PG levels, particularly among individuals with fasting glucose ≥110 mg/dL. Diabetes is a serious worldwide health problem.¹⁶ The number of people with type 2 DM is expected to increase rapidly within the next 25 years, with an estimated 42% increase in developed countries.¹⁷ Hyperglycemia results from a complex interplay between insulin sensitivity and secretion, with a failure of pancreatic beta cells to compensate sufficiently for the increased insulin requirement induced by insulin resistance.¹⁸ Chronic hyperglycemia causes diabetes-associated complications²; thus, strict control of blood glucose may be essential in impaired fasting glucose or impaired glucose tolerance.

Soy protein and peptides as major dietary vegetable proteins have been reported to produce various physiological effects, including weight loss in obese subject and reductions of insulin resistance, cholesterol, and blood pressure.^8

–11 Many intervention studies have reported the effect of soy or soy-derived products on glucose metabolism in humans. However, the effects are still controversial.^19,20 A study by Tsai et al.²¹ observed that in obese subjects with type 2 DM, adding soy polysaccharide (10 g) to a standard test meal significantly reduced the increase in postprandial serum glucose and triacylglycerol concentrations. This effect appears to have been due to smaller increases in glucagon and pancreatic polypeptide and larger increases in somatostatin concentrations; there was no significant effect on serum insulin concentrations. Taniguchi et al.²² showed that consuming naturally viscous vegetables (50 g of natto, 60 g of Japanese yams, and 40 g of okra) with white rice reduced acute glycemia and insulinemia. Fujita et al.²³ demonstrated that soybean-derived Touchi extract, an α-glucosidase inhibitor, appears to exert extensive and useful effects in subjects with borderline and mild diabetes. Lui et al.²⁴ reported that soybean supplementation (15 g of soy protein + 100 mg of isoflavone) for 6 months did not improve glycemic control or insulin sensitivity but did improve 2-hour PG.

The meta-analysis published by Anderson et al.²⁵ in 1995 reported the effect of soy supplement (47 g/day) on the blood lipid level: significant reductions in total cholesterol (23.2 mg/dL), LDL cholesterol (21.7 mg/dL), and triglycerides (13.3 mg/dL) but a nonsignificant increase in HDL cholesterol (1.2 mg/dL). In another study, meta-regression analyses showed a dose–response relation of soy protein and isoflavone supplementation with the changes in serum lipids and showed that soy protein supplementation reduced serum lipids in adults regardless of hypercholesterolemia.²⁶ Anderson et al.²⁷ studied the effect of soy protein at 1 g of protein/kg of body weight for 8 weeks in type 2 DM subjects with obesity and hypertension and observed a reduction in total cholesterol and triacylglycerol concentrations and the improvement of hyperlipidemia. Hermansen et al.¹⁰ also reported that type 2 DM subjects treated with a soy-based dietary supplement (50 g of isolated soy protein, 165 mg of isoflavone, and 20 g of soy cotyledon fiber) for 6 weeks showed significant reduction in LDL cholesterol (10%), the LDL/HDL ratio (12%), and apolipoprotein B100 levels (30%). Such changes in lipid levels have been shown to be associated with less coronary artery disease.^28
–30 The reduction of apolipoprotein B levels may be associated with the peroxisome proliferator-activated receptor γ expression, activated by soy supplemention.³¹ In our study, we observed a significant reduction in apolipoprotein B levels (6%) after black soy peptide supplement.

Anthocyanins in the black soybean seed coat play a role in regulating glucose transporter 4 and preventing insulin resistance as well as pancreatic apoptosis, supporting the use of black soybean as a potential antidiabetes treatment.³² A few studies have also reported that black soy peptides possess anti-obesity and hypolipidemic actions.^33
–35 Kim et al.³³ showed that peptides derived from black soybean hydrolysate could inhibit adipogenesis in an in vitro model, suggesting a potential anti-obesity effect through control of adiposity. Similarly, Jang et al.³⁶ reported that novel peptide mixtures derived from black soybean inhibited diet-induced obesity in mice by activating leptin-like signaling and AMP-dependent protein kinase. In addition, recent studies have suggested that black soy peptide may activate the insulin-signaling pathway and improve the endoplasmic reticulum stress, making it a potential therapeutic peptide for type 2 DM.³⁶

In our study, we additionally subdivided study subjects according to the glucose levels <110 mg/dL or greater and performed a paired t test and independent t test. We found the significant differences in subjects with glucose levels ≥110 mg/dL before and after the intervention: for glucose, 0 week of 126.6 ± 2.92 mg/dL and 12 weeks of 121.7 ± 4.68 mg/dL, two-tailed P = .098, one-tailed P = .049; for 2-hour PG, 0 week of 243.1 ± 20.44 mg/dL and 12 weeks of 201.9 ± 17.45 mg/dL, two-tailed P = .012, one-tailed P = .006. The present randomized, controlled trial conducted in Korean adults demonstrated that black soy peptide supplement may reduce fasting glucose levels and 2-hour PG levels in subjects with fasting glucose ≥110 mg/dL. However, hemoglobin A1c levels were not significantly changed by the dietary intervention in the present study. Larger clinical studies with subjects who have high fasting glucose levels are needed to confirm the beneficial effects of black soy peptide on glucose and related biomarkers.

Footnotes

Acknowledgments

This work was supported by Nongshim Co., Ltd. and the National Research Foundation, Ministry of Education, Science and Technology (Mid-career Researcher Program grants 2010-0015017 and M10642120002-06N4212-00210).

Author Disclosure Statement

No competing financial interests exist.

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