Prediabetes
Conditions
Keywords
Dairy, Milk, Glucose, Postprandial, Hyperglycemia, Prediabetes, Blood glucose, Oxidative stress, Vascular health, Vascular function
Brief summary
Cardiovascular disease (CVD) is the leading cause of death in the United States. Short-term increases in blood sugar, or postprandial hyperglycemia (PPH), affect blood vessel function and increase the risk of CVD. Greater intakes of dairy foods have been associated with a lower risk of CVD, but whether these effects occur directly or indirectly by displacing foods in the diet that might increase CVD risk is unclear. The health benefits of dairy on heart health are at least partly attributed to its ability to limit PPH and resulting PPH-mediated responses leading to vascular dysfunction. This provides rationale to further investigate dairy as a dietary strategy to reduce PPH and risk for CVD. The objective of this study is to define the extent to which dairy milk, and its whey and casein protein fractions, protect against postprandial vascular dysfunction by reducing oxidative stress responses that limit nitric oxide bioavailability to the vascular endothelium in adults with prediabetes.
Detailed description
This study consists of four, 3-hour postprandial trials in response to consuming the following dietary treatments: 1. oral glucose challenge, 2. oral glucose challenge in combination with non-fat milk, 3. oral glucose challenge in combination with whey protein isolate, and 4. oral glucose challenge in combination with sodium caseinate. For three days preceding each trial, participants will be provided all meals to standardize physiologic responses to test meals. On each trial day, vascular function will be assessed and blood samples collected prior to and at 30 minute intervals for 3 hours following test meal ingestion.
Interventions
OTHERGlucose
Following baseline measurements, participants will consume a 75 g glucose solution within five minutes.
Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of non-fat milk within five minutes.
OTHERGlucose with Whey Protein Isolate
Following baseline measurements, participants will consume 75 g glucose and whey protein isolate dissolved in 2 cups water within five minutes.
OTHERGlucose with Sodium Caseinate
Following baseline measurements, participants will consume 75 g glucose and sodium caseinate dissolved in 2 cups water within five minutes.
Sponsors
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. hemoglobin A1c 5.7-6.4% 2. non-dietary supplement user 3. no medications affecting vasodilation, inflammation, or energy metabolism 4. no CVD 5. nonsmokers 6. individuals having blood pressure \<140/90 mmHg and total cholesterol \<240 mg/dL
Exclusion criteria
1. unstable weight (±2 kg) 2. vegetarian or dairy allergy 3. alcohol intake \>3 drinks/day or \>10 drinks/week 4. ≥7 hours/week of aerobic activity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vascular Endothelial Function | Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes) | Flow mediated dilation (FMD) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Glucose | Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline) | Plasma glucose concentration from 0-180 minutes |
| Malondialdehyde (MDA) | Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline) | Plasma MDA measured as MDA AUC from 0-180 minutes |
| Arginine (ARG) | ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma arginine concentration, calculated as ARG AUC from 0-180 minutes |
| Asymmetric Dimethylarginine/Arginine (ADMA/ARG) | ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma ADMA/arginine concentration, calculated as ADMA/ARG AUC from 0-180 minutes |
| Symmetric Dimethylarginine/Arginine (SDMA/ARG) | SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma SDMA/arginine concentration, calculated as SDMA/ARG AUC from 0-180 minutes |
| Nitrite/Nitrate (NOx) | Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline) | NOx AUC for 0-180 minutes |
| Insulin | Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma insulin concentration, calculated as insulin AUC from 0-180 minutes |
| Cholecystokinin (CCK) | CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma CCK concentration, calculated as CCK AUC from 0-180 minutes |
| 8-isoprostaglandin-F2a | 8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma 8-isoprostaglandin-F2a concentration, calculated as 8-isoprostaglandin-F2a AUC from 0-180 minutes |
| 8-isoprostaglandin-F2a/Arachidonic Acid | 8-isoprostaglandin-F2a/Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma 8-isoprostaglandin-F2a/Arachidonic acid concentration, calculated as 8-isoprostaglandin-F2a/Arachidonic acid AUC from 0-180 minutes |
| Arachidonic Acid | Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Arachidonic acid concentration, calculated as Arachidonic acid AUC from 0-180 minutes |
| Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2) | Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline) | Plasma BH4/BH2 concentration, calculated as BH4/BH2 AUC from 0-180 minutes |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Each study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.
Glucose: Following baseline measurements, participants will consume a 75 g glucose solution within five minutes.
Glucose with Non-fat Milk: Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of non-fat milk within five minutes.
Glucose with Whey Protein Isolate: Following baseline measurements, participants will consume 75 g glucose and whey protein isolate dissolved in 2 cups water within five minutes.
Glucose with Sodium Caseinate: Following baseline measurements, participants will consume 75 g glucose and sodium caseinate dissolved in 2 cups water within five minutes. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 23 Participants | — |
| Age, Continuous | 33 years STANDARD_DEVIATION 9 | — |
| Body Mass Index | 31.6 kg/m^2 STANDARD_DEVIATION 4.3 | — |
| Diastolic Blood Pressure | 83 mmHg STANDARD_DEVIATION 7.5 | — |
| Fasting Glucose | 5.8 mmol/L STANDARD_DEVIATION 0.4 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 23 participants | — |
| Sex: Female, Male Female | 6 Participants | — |
| Sex: Female, Male Male | 17 Participants | — |
| Systolic Blood Pressure | 125.3 mmHg STANDARD_DEVIATION 9.3 | — |
| Total Cholesterol | 4.6 mmol/L STANDARD_DEVIATION 0.8 | — |
| Waist Circumference | 106.9 cm STANDARD_DEVIATION 14.6 | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 0 / 23 | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Vascular Endothelial Function
Flow mediated dilation (FMD) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline)
Time frame: Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Vascular Endothelial Function | -307 %*min | Standard Error 67.1 |
| Glucose With Non-fat Milk | Vascular Endothelial Function | -34.8 %*min | Standard Error 62 |
| Glucose With Whey Protein Isolate | Vascular Endothelial Function | -36.8 %*min | Standard Error 63.3 |
| Glucose With Sodium Caseinate | Vascular Endothelial Function | -110 %*min | Standard Error 49.8 |
Secondary
8-isoprostaglandin-F2a
Plasma 8-isoprostaglandin-F2a concentration, calculated as 8-isoprostaglandin-F2a AUC from 0-180 minutes
Time frame: 8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | 8-isoprostaglandin-F2a | 2162.2 pg/mL*min | Standard Error 436.5 |
| Glucose With Non-fat Milk | 8-isoprostaglandin-F2a | -824.14 pg/mL*min | Standard Error 368.68 |
| Glucose With Whey Protein Isolate | 8-isoprostaglandin-F2a | -18.75 pg/mL*min | Standard Error 498.8 |
| Glucose With Sodium Caseinate | 8-isoprostaglandin-F2a | 229.14 pg/mL*min | Standard Error 484.62 |
Secondary
8-isoprostaglandin-F2a/Arachidonic Acid
Plasma 8-isoprostaglandin-F2a/Arachidonic acid concentration, calculated as 8-isoprostaglandin-F2a/Arachidonic acid AUC from 0-180 minutes
Time frame: 8-isoprostaglandin-F2a/Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | 8-isoprostaglandin-F2a/Arachidonic Acid | 10129 (pg/mL)/(ug/mL)*min | Standard Error 1613.7 |
| Glucose With Non-fat Milk | 8-isoprostaglandin-F2a/Arachidonic Acid | -1655.2 (pg/mL)/(ug/mL)*min | Standard Error 1477.1 |
| Glucose With Whey Protein Isolate | 8-isoprostaglandin-F2a/Arachidonic Acid | 2422.3 (pg/mL)/(ug/mL)*min | Standard Error 2030.6 |
| Glucose With Sodium Caseinate | 8-isoprostaglandin-F2a/Arachidonic Acid | 3907.6 (pg/mL)/(ug/mL)*min | Standard Error 2378.7 |
Secondary
Arachidonic Acid
Arachidonic acid concentration, calculated as Arachidonic acid AUC from 0-180 minutes
Time frame: Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Arachidonic Acid | -2570 ug/mL*min | Standard Error 451.86 |
| Glucose With Non-fat Milk | Arachidonic Acid | -1358.4 ug/mL*min | Standard Error 497.54 |
| Glucose With Whey Protein Isolate | Arachidonic Acid | -2762.6 ug/mL*min | Standard Error 529.07 |
| Glucose With Sodium Caseinate | Arachidonic Acid | -2752.0 ug/mL*min | Standard Error 462.74 |
Secondary
Arginine (ARG)
Plasma arginine concentration, calculated as ARG AUC from 0-180 minutes
Time frame: ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Arginine (ARG) | -3922 umol/L*min | Standard Error 486 |
| Glucose With Non-fat Milk | Arginine (ARG) | -1235 umol/L*min | Standard Error 565 |
| Glucose With Whey Protein Isolate | Arginine (ARG) | 195 umol/L*min | Standard Error 632 |
| Glucose With Sodium Caseinate | Arginine (ARG) | -189 umol/L*min | Standard Error 628 |
Secondary
Asymmetric Dimethylarginine/Arginine (ADMA/ARG)
Plasma ADMA/arginine concentration, calculated as ADMA/ARG AUC from 0-180 minutes
Time frame: ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Asymmetric Dimethylarginine/Arginine (ADMA/ARG) | 275 (nmol/L)/(umol/L)*min | Standard Error 34 |
| Glucose With Non-fat Milk | Asymmetric Dimethylarginine/Arginine (ADMA/ARG) | 55 (nmol/L)/(umol/L)*min | Standard Error 43 |
| Glucose With Whey Protein Isolate | Asymmetric Dimethylarginine/Arginine (ADMA/ARG) | 47 (nmol/L)/(umol/L)*min | Standard Error 38 |
| Glucose With Sodium Caseinate | Asymmetric Dimethylarginine/Arginine (ADMA/ARG) | 25 (nmol/L)/(umol/L)*min | Standard Error 37 |
Secondary
Cholecystokinin (CCK)
Plasma CCK concentration, calculated as CCK AUC from 0-180 minutes
Time frame: CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Cholecystokinin (CCK) | 89.67 pmol/L*min | Standard Error 117.52 |
| Glucose With Non-fat Milk | Cholecystokinin (CCK) | 422.87 pmol/L*min | Standard Error 182.43 |
| Glucose With Whey Protein Isolate | Cholecystokinin (CCK) | 352.5 pmol/L*min | Standard Error 154.03 |
| Glucose With Sodium Caseinate | Cholecystokinin (CCK) | 519.94 pmol/L*min | Standard Error 202.36 |
Secondary
Insulin
Plasma insulin concentration, calculated as insulin AUC from 0-180 minutes
Time frame: Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Insulin | 8179.7 uIU/mL*min | Standard Error 904.91 |
| Glucose With Non-fat Milk | Insulin | 8196.1 uIU/mL*min | Standard Error 882.03 |
| Glucose With Whey Protein Isolate | Insulin | 8654.6 uIU/mL*min | Standard Error 804.32 |
| Glucose With Sodium Caseinate | Insulin | 8656.9 uIU/mL*min | Standard Error 869.98 |
Secondary
Malondialdehyde (MDA)
Plasma MDA measured as MDA AUC from 0-180 minutes
Time frame: Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Malondialdehyde (MDA) | 66.5 umol/L*min | Standard Error 6.06 |
| Glucose With Non-fat Milk | Malondialdehyde (MDA) | 43.2 umol/L*min | Standard Error 4.27 |
| Glucose With Whey Protein Isolate | Malondialdehyde (MDA) | 46.4 umol/L*min | Standard Error 4.34 |
| Glucose With Sodium Caseinate | Malondialdehyde (MDA) | 45.1 umol/L*min | Standard Error 3.56 |
Secondary
Nitrite/Nitrate (NOx)
NOx AUC for 0-180 minutes
Time frame: Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Nitrite/Nitrate (NOx) | -1363 umol/L*min | Standard Error 285 |
| Glucose With Non-fat Milk | Nitrite/Nitrate (NOx) | 347 umol/L*min | Standard Error 329 |
| Glucose With Whey Protein Isolate | Nitrite/Nitrate (NOx) | -21 umol/L*min | Standard Error 207 |
| Glucose With Sodium Caseinate | Nitrite/Nitrate (NOx) | -57.2 umol/L*min | Standard Error 237 |
Secondary
Plasma Glucose
Plasma glucose concentration from 0-180 minutes
Time frame: Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Plasma Glucose | 5828 mg/dL*min | Standard Error 669 |
| Glucose With Non-fat Milk | Plasma Glucose | 4032 mg/dL*min | Standard Error 702 |
| Glucose With Whey Protein Isolate | Plasma Glucose | 3340 mg/dL*min | Standard Error 619 |
| Glucose With Sodium Caseinate | Plasma Glucose | 3640 mg/dL*min | Standard Error 550 |
Secondary
Symmetric Dimethylarginine/Arginine (SDMA/ARG)
Plasma SDMA/arginine concentration, calculated as SDMA/ARG AUC from 0-180 minutes
Time frame: SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Symmetric Dimethylarginine/Arginine (SDMA/ARG) | 175 (nmol/L)/(umol/L)*min | Standard Error 14 |
| Glucose With Non-fat Milk | Symmetric Dimethylarginine/Arginine (SDMA/ARG) | 31 (nmol/L)/(umol/L)*min | Standard Error 13 |
| Glucose With Whey Protein Isolate | Symmetric Dimethylarginine/Arginine (SDMA/ARG) | 4 (nmol/L)/(umol/L)*min | Standard Error 16 |
| Glucose With Sodium Caseinate | Symmetric Dimethylarginine/Arginine (SDMA/ARG) | -17 (nmol/L)/(umol/L)*min | Standard Error 12 |
Secondary
Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2)
Plasma BH4/BH2 concentration, calculated as BH4/BH2 AUC from 0-180 minutes
Time frame: Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glucose | Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2) | -47 ratio*min | Standard Error 119 |
| Glucose With Non-fat Milk | Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2) | 78 ratio*min | Standard Error 99 |
| Glucose With Whey Protein Isolate | Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2) | 171 ratio*min | Standard Error 122 |
| Glucose With Sodium Caseinate | Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2) | 131 ratio*min | Standard Error 67 |