Oleocanthal Rich Olive Oil Acute Effects on Hyperglycemia and Platelet Activation in T2DM

Study Overview
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Brief Summary
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This is a pilot acute dietary intervention study with a randomized cross-over design aiming to investigate whether acute supplementation of extra virgin olive oil (EVOO) rich in oleocanthal could attenuate postprandial hyperglycemia and activation of platelets in T2DM patients. For this reason, non-insulin dependent diabetic patients (10-15) will be randomly assigned to consume in five different days white bread (50 g CHO) with butter, butter with ibuprofen, refined olive oil and olive oil with oleocanthal (250 mg/Kg 500 mg/Kg). Blood samples will be collected pre- and post-intervention up to 4 hours in order to determine platelet aggregation, postprnadial glycemia, lipemia, inflammation and oxidative stress. Taking into account the strong anti-inflammatory and anti-platelet properties of oleocanthal, this study will assess whether oleocanthal-rich olive oils could exert similar effects under real in vivo conditions in T2DM patients. It will also assess whether these effects are achieved through improvement of postprandial glycemia and lipemia.

Official Title
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Acute Effect of Oleocanthal Rich Extra-virgin Olive Oil on Postpranial Hyperglycemia and Platelet Activation of T2DM Patients

Conditions
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Diabetes Mellitus, Adult-Onset, Platelet Dysfunction, Postprandial Hyperglycemia, Lipidemia, Inflammation, Oxidative Stress

Intervention / Treatment
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* Other: White bread
* Other: Butter
* Other: Refined olive oil
* Other: EVOO with 250 mg/kg oleocanthal
* Other: EVOO with 500 mg/kg oleocanthal
* Other: Ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients diagnosed with T2DM stable weight the last two months smokers or not no restriction regarding the menopause Exclusion Criteria: insulin therapy antiplatelet, anti-coagulant, anti-inflammatory and anti-depressant medication chronic inflammatory disease autoimmune diseases cancer uncontrolled thyroid disease. supplement consumption the last two months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Acute postprandial study with a randomized cross-over design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>100g white bread plus 40ml butter | Other: White bread<br>* White bread (120g) containing 54 g CHO<br>Other: Butter<br>* Butter 39 g<br>|
| Experimental: Positive control<br>100g white bread plus 40ml butter and 400mg ibuprofen | Other: White bread<br>* White bread (120g) containing 54 g CHO<br>Other: Butter<br>* Butter 39 g<br>Other: Ibuprofen<br>* Ibuprofen 400 mg<br>|
| Experimental: Refined olive oil<br>100g white bread plus 40ml refined olive oil | Other: White bread<br>* White bread (120g) containing 54 g CHO<br>Other: Refined olive oil<br>* Refined olive oil (40 ml).<br>|
| Experimental: EVOO with moderate concentration of oleocanthal<br>100g white bread plus 40ml EVOO containing 250 mg/kg oleocanthal | Other: White bread<br>* White bread (120g) containing 54 g CHO<br>Other: EVOO with 250 mg/kg oleocanthal<br>* Extra virgin olive oil containing 250 mg/kg oleocanthal.<br>|
| Experimental: EVOO with high concentration of oleocanthal<br>100g white bread plus 40ml EVOO containing 500 mg/kg oleocanthal | Other: White bread<br>* White bread (120g) containing 54 g CHO<br>Other: EVOO with 500 mg/kg oleocanthal<br>* Extra virgin olive oil containing 500 mg/kg oleocanthal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of ADP-induced platelet aggregation at 90 min after meals consumption | EC50 (microM) of ADP induced platelet aggregation will be assessed by light transmittance aggregometry | 0 and 90 after the consumption of each type of meal | 
| Change from baseline of ADP-induced platelet aggregation at 240 min after meals consumption | EC50 (microM) of ADP induced platelet aggregation will be assessed by light transmittance aggregometry | 0 and 240 after the consumption of each type of meal | 
| Change from baseline of TRAP-induced platelet aggregation at 90 min after meals consumption | EC50 (microM) of TRAP induced platelet aggregation will be assessed by light transmittance aggregometry | 0 and 90 after the consumption of each type of meal | 
| Change from baseline of TRAP-induced platelet aggregation at 240 min after meals consumption | EC50 (microM) of TRAP induced platelet aggregation will be assessed by light transmittance aggregometry | 0 and 240 after the consumption of each type of meal | 
| Change from baseline of PAF-induced platelet aggregation at 90 min after meals consumption | EC50 (microM) of PAF induced platelet aggregation will be assessed by light transmittance aggregometry | 0 and 90 after the consumption of each type of meal | 
| Change from baseline of PAF-induced platelet aggregation at 240 min after meals consumption | EC50 (microM) of PAF induced platelet aggregation will be assessed by light transmittance aggregometry | 0 and 240 after the consumption of each type of meal | 
| Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Glucose | iAUC of postprandial glucose will be calculated by serum glucose levels (mg/dL) which will be assessed by commercially available kits | 0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal | 
| Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Insulin | iAUC of postprandial insulin will be calculated by serum insulin levels (mIU/L) which will be assessed by commercially available kits | 0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal | 
| Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Triglycerides | iAUC of postprandial triglycerides will be calculated by serum triglyceride levels (mg/dL) which will be assessed by commercially available kits | 0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of IL-6 | iAUC of postprandial IL-6 will be calculated by serum IL-6 levels (mg/dL) which will be assessed by commercially available ELISA kits | 0, 60, 120, 180, 240 min after the consumption of each meal | 
| Incremental Area Under the Plasma Concentration Versus Time Curve (AUC) of Protein Carbonyls | iAUC of postprandial protein carbonyls will be calculated by plasma protein carbonyl levels (mg/dL) which will be determined by a photometric assay | 0, 60, 120, 180, 240 min after the consumption of each meal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oleocanthal, type 2 diabetes mellitus, diabetic platelet, platelet aggregation, oxidative stress, inflammation, postrpandial, hyperglycemia, extra virgin olive oil, polyphenols, dyslipidemia