Type 2 Diabetes Mellitus
Conditions
Keywords
genistein, daidzein, impaired glucose regulation, glucose metabolism, lipids metabolism, inflammation, women
Brief summary
Many studies showed that soy foods or soy isoflavones can lower the risk of cardiovascular disease (CVD), osteoporosis and some cancers, but few human studies assessed effects of purified isoflavone components (genistein and daidzein) on glucose metabolism. This double-blinded, randomized, placebo-controlled trial will examine the effects of purified genistein and daidzein on glucose metabolism in prediabetic or diabetic women. One hundred and eighty eligible women age 30-70 years(without any treatment of diabetic drugs) will be recruited and randomly allocated into the following three arms: Placebo (10g isolated soy protein, ISP); Genistein (10g ISP + 50mg genistein); Daidzein (10g ISP + 50mg daidzein) per day for 6 mo. Fasting glucose, lipids, insulin, inflammation marks and post-load for glucose and insulin will be determined at 0, 3th, and 6th month. Changes in these indices will be compared among the three groups.
Detailed description
Subjects were Chinese adult women, age 30-70 year, with an FG concentration ranging from 5.6 to 7.0 mmol/L or 2-h PG concentration ranging from 7.8-11.0 mmol/L or with newly diagnosed diabetes not requiring medication treatment according to a doctor's suggestion or participants did not willing to take medication themselves, and managed their diabetes just with a stable diet and exercise. Women were excluded if they had a history of coronary heart disease, stoke, thyroid disease, severe liver, lung, or gastrointestinal tract diseases; were currently or in the past 8 weeks used hypoglycemic or lipid-lowering or weight-reduction agents; were occurrence of diabetic complications; use of hormone replacement therapy; allergy to soy;were long-term antibiotics users.
Interventions
DIETARY_SUPPLEMENTPlacebo
10g soy protein isolated per day
DIETARY_SUPPLEMENTDaidzein
50mg daidzein +10g soy protein isolated per day
DIETARY_SUPPLEMENTGenistein
50mg genistein +10g soy protein isolated per day
Sponsors
Chinese Nutrition Society
Danone Institute International
Department of Health of Guangdong Province
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chinese women aged 30-70 y * Fasting glucose \>=5.6 mmol/l; post-load glucose \>=7.8 mmol/l
Exclusion criteria
* Diabetes renal diseases * Confirmed CVD, chronic liver,kidney diseases,Thyroid disease * Medications affecting glucose or lipid metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Low Density Lipoprotein Cholesterol | Baseline, 6 months | (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in QUICKI | Baseline, 6 months | QUICKI is the abbreviation of Quantitative Insulin Sensitivity Check Index,and it is a marker to evaluate insulin sensitivity in HOMA model.It is calculated by using the following equation: 1/(logFIns +logFG),where FIns represents fasting insulin in microunits per milliliter, and FG is in millimoles per liter. The percentage change was caculated as (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in Total Cholesterol | Baseline, 6 months | (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in Triglyceride | Baseline, 6 months | (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in High Density Lipoprotein Cholesterol | Baseline, 6 months | (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in Fasting Plasma Glucose | Baseline,6 months | (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in 120-minutes Postload Plasma Glucose | Baseline, 6 months | (6th month value-baseline value)/baseline\*100% |
| Percentage Change in HbA1C | Baseline, 6 months | (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in AUC of Glucose | Baseline, 6 months | values were from 75g glucose oral glucose tolerance test and caculated as (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in Fasting Plasma Insulin | Baseline, 6 months | (6th month value-baseline value)/baseline value\*100% |
| Percentage Change in HOMA-IR | Baseline, 6 months | HOMA-IR was calculated with the homeostasis model assessment for insulin resistance,and it is caculated as the following equation: HOMA-IR=FIns×FG/22.5, where FIns represents fasting insulin in microunits per milliliter, and FG is in millimoles per liter. The percentage change was caculated as (6th month value-baseline value)/baseline value\*100% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Daidzein | 3 months | Urinary daidzein excretion |
| Urinary Genistein | 3 months | Urinary genistein excretion |
| Total Energy Intake at Follow-up | an average of the 24 weeks follow-up period which were evalutated on baseline,12 week and 24 week. | The energy intake was evaluated by 3 days dietary records. |
| Total Urinary Isoflavones | 3 months | — |
Countries
China
Participant flow
Recruitment details
the recruitment period last about half a year,and the types of location are clinic of endocrinology and nutritional clinic
Participants by arm
| Arm | Count |
|---|---|
| Placebo the placebo group were given 10g soy protein isolated without isoflavones | 54 |
| Daidzein Daidzein group were given 10g soy protein isolated and 50mg purify daidzein | 55 |
| Genistein Genistein group were given 10g soy protein isolated and 50mg purify genistein | 56 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 0 |
| Overall Study | Other: Colon cancer | 1 | 0 | 0 |
| Overall Study | Other:Depression | 1 | 0 | 0 |
| Overall Study | Other: Stroke | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Daidzein | Genistein | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 14 Participants | 11 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 42 Participants | 43 Participants | 128 Participants |
| Age Continuous | 56.36 years STANDARD_DEVIATION 9.9 | 57.02 years STANDARD_DEVIATION 9.68 | 56.31 years STANDARD_DEVIATION 11.07 | 56.57 years STANDARD_DEVIATION 10.17 |
| Region of Enrollment China | 55 participants | 56 participants | 54 participants | 165 participants |
| Sex: Female, Male Female | 55 Participants | 56 Participants | 54 Participants | 165 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 54 | 4 / 55 | 2 / 56 |
| serious Total, serious adverse events | 0 / 54 | 0 / 55 | 0 / 56 |
Outcome results
Primary
Percentage Change in 120-minutes Postload Plasma Glucose
(6th month value-baseline value)/baseline\*100%
Time frame: Baseline, 6 months
Population: All participants were determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in 120-minutes Postload Plasma Glucose | -4.90 percentage of change | Standard Deviation 20.67 |
| Daidzein Group | Percentage Change in 120-minutes Postload Plasma Glucose | -3.13 percentage of change | Standard Deviation 20.6 |
| Geinstein Group | Percentage Change in 120-minutes Postload Plasma Glucose | -5.59 percentage of change | Standard Deviation 24.23 |
p-value: <0.0595% CI: [-11.9308, 8.3916]ANOVA
p-value: <0.0595% CI: [-9.4232, 10.8091]ANOVA
p-value: <0.0595% CI: [-7.6067, 12.5318]ANOVA
Primary
Percentage Change in AUC of Glucose
values were from 75g glucose oral glucose tolerance test and caculated as (6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of patticipants was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in AUC of Glucose | -6.23 percentage of change | Standard Deviation 14.06 |
| Daidzein Group | Percentage Change in AUC of Glucose | -3.27 percentage of change | Standard Deviation 16.98 |
| Geinstein Group | Percentage Change in AUC of Glucose | -5.24 percentage of change | Standard Deviation 17.96 |
p-value: <0.0595% CI: [-10.5857, 4.6535]ANOVA
p-value: <0.0595% CI: [-8.583, 6.5886]ANOVA
p-value: <0.0595% CI: [-5.5817, 9.5195]ANOVA
Primary
Percentage Change in Fasting Plasma Glucose
(6th month value-baseline value)/baseline value\*100%
Time frame: Baseline,6 months
Population: the number of participants for analysis was determined by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in Fasting Plasma Glucose | -1.80 percentage of change | Standard Deviation 13.5 |
| Daidzein Group | Percentage Change in Fasting Plasma Glucose | -1.00 percentage of change | Standard Deviation 12.61 |
| Geinstein Group | Percentage Change in Fasting Plasma Glucose | -4.89 percentage of change | Standard Deviation 11.79 |
Comparison: Null hypothesis: There are no difference in the difference of changes in plasma glucose.~Power calculation: The sample size of 55 subjects per group provided about 90% power to detect a significant change in the FG concentration of 8 mg/dL (7%) by using a general assumption of a 2-tailed a level of 0.05 and allowing for a 20% withdrawal rate.p-value: <0.0595% CI: [-6.6569, 5.0607]ANOVA
p-value: <0.0595% CI: [-2.7486, 8.9171]ANOVA
p-value: <0.0595% CI: [-1.9234, 9.6881]ANOVA
Primary
Percentage Change in Fasting Plasma Insulin
(6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of participants was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in Fasting Plasma Insulin | 25.27 percentage of change | Standard Deviation 114.23 |
| Daidzein Group | Percentage Change in Fasting Plasma Insulin | 21.41 percentage of change | Standard Deviation 91.23 |
| Geinstein Group | Percentage Change in Fasting Plasma Insulin | 6.06 percentage of change | Standard Deviation 78.26 |
p-value: <0.05Kruskal-Wallis
Primary
Percentage Change in HbA1C
(6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of participants analyzed was determinted by intention to treat.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in HbA1C | -1.38 percentage of change | Standard Deviation 7.17 |
| Daidzein Group | Percentage Change in HbA1C | -1.37 percentage of change | Standard Deviation 5.99 |
| Geinstein Group | Percentage Change in HbA1C | -1.30 percentage of change | Standard Deviation 9.29 |
p-value: <0.0595% CI: [-6.174, 0.8243]ANOVA
p-value: <0.0595% CI: [-3.5428, 3.5194]ANOVA
p-value: <0.0595% CI: [-6.202, 0.8288]ANOVA
Primary
Percentage Change in High Density Lipoprotein Cholesterol
(6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in High Density Lipoprotein Cholesterol | 3.18 Percentage of change | Standard Deviation 20.4 |
| Daidzein Group | Percentage Change in High Density Lipoprotein Cholesterol | 1.36 Percentage of change | Standard Deviation 15.21 |
| Geinstein Group | Percentage Change in High Density Lipoprotein Cholesterol | 2.15 Percentage of change | Standard Deviation 14.54 |
p-value: <0.0595% CI: [-6.0057, 9.6426]ANOVA
p-value: <0.0595% CI: [-6.7619, 8.817]ANOVA
p-value: <0.0595% CI: [-8.5442, 6.9624]ANOVA
Primary
Percentage Change in HOMA-IR
HOMA-IR was calculated with the homeostasis model assessment for insulin resistance,and it is caculated as the following equation: HOMA-IR=FIns×FG/22.5, where FIns represents fasting insulin in microunits per milliliter, and FG is in millimoles per liter. The percentage change was caculated as (6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of participants for analysis was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in HOMA-IR | 22.83 Percentage of change | Standard Deviation 107.41 |
| Daidzein Group | Percentage Change in HOMA-IR | 21.60 Percentage of change | Standard Deviation 98.88 |
| Geinstein Group | Percentage Change in HOMA-IR | -0.22 Percentage of change | Standard Deviation 64.03 |
p-value: <0.05Kruskal-Wallis
Primary
Percentage Change in Low Density Lipoprotein Cholesterol
(6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of participants for analysis was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in Low Density Lipoprotein Cholesterol | 1.08 Percentage of change | Standard Deviation 24.46 |
| Daidzein Group | Percentage Change in Low Density Lipoprotein Cholesterol | -0.93 Percentage of change | Standard Deviation 21.21 |
| Geinstein Group | Percentage Change in Low Density Lipoprotein Cholesterol | 1.86 Percentage of change | Standard Deviation 19.39 |
p-value: <0.0595% CI: [-8.0721, 12.0964]ANOVA
p-value: <0.0595% CI: [-10.8111, 9.2679]ANOVA
p-value: <0.0595% CI: [-12.7767, 7.2092]ANOVA
Primary
Percentage Change in QUICKI
QUICKI is the abbreviation of Quantitative Insulin Sensitivity Check Index,and it is a marker to evaluate insulin sensitivity in HOMA model.It is calculated by using the following equation: 1/(logFIns +logFG),where FIns represents fasting insulin in microunits per milliliter, and FG is in millimoles per liter. The percentage change was caculated as (6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of participants for analysis was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in QUICKI | 2.32 Percentage of change | Standard Deviation 19.47 |
| Daidzein Group | Percentage Change in QUICKI | 0.18 Percentage of change | Standard Deviation 15.6 |
| Geinstein Group | Percentage Change in QUICKI | 6.29 Percentage of change | Standard Deviation 17.77 |
p-value: <0.05Kruskal-Wallis
Primary
Percentage Change in Total Cholesterol
(6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of participants for analysis was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in Total Cholesterol | 2.85 Percentage of change | Standard Deviation 40.06 |
| Daidzein Group | Percentage Change in Total Cholesterol | -0.59 Percentage of change | Standard Deviation 11.9 |
| Geinstein Group | Percentage Change in Total Cholesterol | -0.64 Percentage of change | Standard Deviation 15.83 |
p-value: <0.0595% CI: [-8.444, 15.318]ANOVA
p-value: <0.0595% CI: [-8.3475, 15.3092]ANOVA
p-value: <0.0595% CI: [-11.7296, 11.8174]ANOVA
Primary
Percentage Change in Triglyceride
(6th month value-baseline value)/baseline value\*100%
Time frame: Baseline, 6 months
Population: The number of participants for analysis was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Percentage Change in Triglyceride | 5.93 Percentage of change | Standard Deviation 45.5 |
| Daidzein Group | Percentage Change in Triglyceride | 3.43 Percentage of change | Standard Deviation 38.9 |
| Geinstein Group | Percentage Change in Triglyceride | -1.56 Percentage of change | Standard Deviation 39.15 |
p-value: <0.05Kruskal-Wallis
Secondary
Total Energy Intake at Follow-up
The energy intake was evaluated by 3 days dietary records.
Time frame: an average of the 24 weeks follow-up period which were evalutated on baseline,12 week and 24 week.
Population: The number of participants for analysis was determinted by intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Total Energy Intake at Follow-up | 1575 kcal | Standard Deviation 575 |
| Daidzein Group | Total Energy Intake at Follow-up | 1473 kcal | Standard Deviation 294 |
| Geinstein Group | Total Energy Intake at Follow-up | 1579 kcal | Standard Deviation 367 |
p-value: <0.0595% CI: [-99.3, 304.1]ANOVA
p-value: 0.0595% CI: [-203.7, 196.1]ANOVA
p-value: <0.0595% CI: [-305.1, 92.8]ANOVA
Secondary
Total Urinary Isoflavones
Time frame: 3 months
Population: The number of participants for analysis was determinted by the participants who provided the urine samples at the 3-month test.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Total Urinary Isoflavones | 8.538 ug/ml | Standard Deviation 10.153 |
| Daidzein Group | Total Urinary Isoflavones | 25.818 ug/ml | Standard Deviation 31.78 |
| Geinstein Group | Total Urinary Isoflavones | 15.467 ug/ml | Standard Deviation 22.022 |
p-value: <0.0595% CI: [-0.6416, -0.2458]ANOVA
p-value: <0.0595% CI: [-0.3956, -0.0016]ANOVA
p-value: <0.0595% CI: [0.0544, 0.4358]ANOVA
Secondary
Urinary Daidzein
Urinary daidzein excretion
Time frame: 3 months
Population: The number of participants for analysis was determinted by the number of participants who provided urine samples at the 3-month test
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Urinary Daidzein | 3.34 ug/ml | Standard Deviation 4.81 |
| Daidzein Group | Urinary Daidzein | 11.80 ug/ml | Standard Deviation 11.14 |
| Geinstein Group | Urinary Daidzein | 3.73 ug/ml | Standard Deviation 8.83 |
p-value: <0.0595% CI: [-0.8617, -0.4089]ANOVA
p-value: 0.0595% CI: [-0.2003, 0.2568]ANOVA
p-value: <0.0595% CI: [0.4419, 0.8851]ANOVA
Secondary
Urinary Genistein
Urinary genistein excretion
Time frame: 3 months
Population: The number of participants for analysis was determinted by the number of participants who supplied the urine samples at the 3-month test
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group | Urinary Genistein | 1.32 ug/ml | Standard Deviation 1.72 |
| Daidzein Group | Urinary Genistein | 1.89 ug/ml | Standard Deviation 2.59 |
| Geinstein Group | Urinary Genistein | 6.54 ug/ml | Standard Deviation 8.97 |
p-value: <0.0595% CI: [-0.3911, 0.0796]ANOVA
p-value: 0.0595% CI: [-0.8414, -0.3707]ANOVA
p-value: <0.0595% CI: [-0.6804, -0.2202]ANOVA