Type 2 Diabetes
Conditions
Keywords
inflammation, insulin resistance, type 2 diabetes, obesity
Brief summary
This study will help elucidate the mechanism underlying the cardioprotective and anti-diabetes effect of dietary fiber by exploring a comprehensive set of inflammatory and oxidative stress markers, based on a contemporary understanding of this process. In addition, there have been very few studies that explored the immediate change in oxidative stress and incretin secretion after fiber intake. In this study, the investigators will be able assess the short term metabolic impact of dietary fiber at great details. The result will contribute to dietary recommendation or designing of fiber supplementation for prevention/treatment of diabetes, obesity and cardiovascular disease.
Detailed description
Baseline labs include complete blood count (CBC), comprehensive metabolic panel (CMP), Hemoglobin A1C, and lipid profile. All labs will be drawn in the fasting state Visit 1: Subjects will arrive after having fasted overnight (10 hours) at 7 to 7:30 am. An indwelling intravenous cannula will be placed in the anterior cubital vein for blood draws. A blood sample of the research labs and a urine sample will be collected. Blood pressure, heart rate and weight will be measured. Subjects will consume either a High Fat High Calorie (HFHC) meal or HFHC meal plus fiber (FiberOne Original cereal) according to randomization. Fiber will be consumed before and after the HFHC meal (28 grams in total, 14 grams before and after the meal). HFHC meal includes an egg muffin sandwich, a sausage muffin sandwich and two hash browns which contain 88g carbohydrate, 51 g fat (33% saturated) and 34 g protein. 35 ml of blood will be obtained at 1h , 2h, 3h and 5 h and 5 ml at 15 min,30 min,45 min,75 min and 90 min. A total of 165 ml (11 tablespoon) blood will be collected. . Visit 2: Subjects will return 1 week later after overnight fasting (10 hours) at 7 to 7:30 am. Blood pressure, heart rate and weight will be measured. Baseline blood and urine samples will be collected again and subjects will be crossed over to receive the second meal (HFHC only or HFHC with fiber). Visit details are similar to visit 1. After this, the subject will be discharged from the study.
Interventions
DIETARY_SUPPLEMENTdietary fiber
Fiber one supplement (32 grams of fiber) will be consumed with 910 Calorie HFHC meal
OTHERHFHC meal
910 Calorie HFHC meal
Sponsors
University at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women 18 to 80 years of age 2. Non-smoker (last cigarette at least one month ago) 3. Type 2 diabetes for at least 1 year 4. Body mass index \> 30 kg/m2
Exclusion criteria
1. Participation in any other concurrent clinical trials 2. Pregnancy or premenopausal women who are trying to be pregnant 3. Patients who are incompetent to give consent 4. Patients on non-steroidal anti-inflammatory drugs or steroids 5. Concurrent disease that could disrupt intestinal epithelium and increase permeability to endotoxin, ie Celiac and Crohns disease. 6. Hepatic disease (transaminase \> 3 times normal) 7. Renal impairment (serum creatinine \> 1.5 mg/dl) 8. History of drug or alcohol abuse 9. Use of over the counter or prescribed probiotic supplements. 10. Recent or current antibiotic use. 11. Coronary artery disease (CAD): documented by history of myocardial infarction, angioplasty/stent placement, angina, exercise EKG positive for ischemia or angiographic evidence of CAD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Change in From Baseline in Reactive Oxygen Species (ROS) Generation | 5hr | mononuclear cells will be isolated by Ficoll-Hypaque method and ROS will be measured by chemiluminescence as an index of NADPH oxidase activation. Measurment will take place at baseline before the meal intervention and hourly for 5 hrs after the meal. The percent change from baseline at peak effect will be calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Change in From Baseline in Nuclear Factor-Kappa B (NFkB) Activation | 5hr | Nuclear factor-Kappa B (NFkB) activation will be measured at baseline before the meal and hourly up to 5 hrs and percent change from baseline at peak effect is calculated |
| Percent Change Toll Like Receptor-4 (TLR-4) Levels | 5hr | Toll Like Receptor-4 will be measured by Western Blots at baseline before meal intake and hourly up to 5 hrs after meal. Percent change from baseline at peak effect is calculated. |
| Change in Plasma Lipopolysaccharides Level From Baseline. | 5hr | Lipopolysaccharide will be measured by commercially available kit (Cambrex Limulus Amebocyte Lysate kit, Lonza Inc. Walkersville, MD). Measurements will take place at baseline before the meals and hourly for next 5 hrs. Percent change from baseline at peak effect is calculated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Participants All participants will randomly receive HFHC meal with or without dietary fiber supplementation in first visit and the other intervention in the second visit. Total 10 participants in cross-over design study | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Overall Study Participants | — |
|---|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 5 | — |
| Body mass index (BMI) | 34 Kg/m^2 STANDARD_DEVIATION 4 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Peak Change in From Baseline in Reactive Oxygen Species (ROS) Generation
mononuclear cells will be isolated by Ficoll-Hypaque method and ROS will be measured by chemiluminescence as an index of NADPH oxidase activation. Measurment will take place at baseline before the meal intervention and hourly for 5 hrs after the meal. The percent change from baseline at peak effect will be calculated.
Time frame: 5hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Fat High Calorie | Peak Change in From Baseline in Reactive Oxygen Species (ROS) Generation | 224 percentage of change | Standard Error 15 |
| High Fat High Calorie Plus Fiber | Peak Change in From Baseline in Reactive Oxygen Species (ROS) Generation | 167 percentage of change | Standard Error 13 |
Secondary
Change in Plasma Lipopolysaccharides Level From Baseline.
Lipopolysaccharide will be measured by commercially available kit (Cambrex Limulus Amebocyte Lysate kit, Lonza Inc. Walkersville, MD). Measurements will take place at baseline before the meals and hourly for next 5 hrs. Percent change from baseline at peak effect is calculated.
Time frame: 5hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Fat High Calorie | Change in Plasma Lipopolysaccharides Level From Baseline. | 124 percentage of change | Standard Error 10 |
| High Fat High Calorie Plus Fiber | Change in Plasma Lipopolysaccharides Level From Baseline. | 128 percentage of change | Standard Error 11 |
Secondary
Peak Change in From Baseline in Nuclear Factor-Kappa B (NFkB) Activation
Nuclear factor-Kappa B (NFkB) activation will be measured at baseline before the meal and hourly up to 5 hrs and percent change from baseline at peak effect is calculated
Time frame: 5hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Fat High Calorie | Peak Change in From Baseline in Nuclear Factor-Kappa B (NFkB) Activation | 124 percentage of change | Standard Error 14 |
| High Fat High Calorie Plus Fiber | Peak Change in From Baseline in Nuclear Factor-Kappa B (NFkB) Activation | 109 percentage of change | Standard Error 8 |
Secondary
Percent Change Toll Like Receptor-4 (TLR-4) Levels
Toll Like Receptor-4 will be measured by Western Blots at baseline before meal intake and hourly up to 5 hrs after meal. Percent change from baseline at peak effect is calculated.
Time frame: 5hr
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Fat High Calorie | Percent Change Toll Like Receptor-4 (TLR-4) Levels | 181 percentage of change | Standard Error 15 |
| High Fat High Calorie Plus Fiber | Percent Change Toll Like Receptor-4 (TLR-4) Levels | 135 percentage of change | Standard Error 12 |