Modulating Effects of Oil Palm Phenolics in Subjects With Pre-diabetes

Study Overview
=================
Brief Summary
-----------------
Study reported that providing Oil Palm Phenolics to Nile rats blocked diabetes progression in this spontaneous diabetes model. The present study aims to determine the beneficial effects of Oil Palm Phenolics in subjects with pre-diabetes.

Detailed Description
-----------------
Recent studies suggest the potential of polyphenols as a supplementary treatment to delay or prevent the onset of diabetes owing to their biological properties. Polyphenols are natural phytochemical compounds found in fruits and vegetables. The most common group of phenolic compounds in our diet are phenolic acids and flavonoids. The two main classes are hydroxybenzoic acid derivatives and hydroxycinnamic acid derivatives. The anti-hyperglycemic property of polyphenols is mainly contributed by the reduction of dietary carbohydrate absorption through intestines, improvement of β-cell function and insulin action, stimulation of insulin secretion, modulation of the enzymes involved in glucose metabolism, anti-oxidative and anti-inflammatory effects. The key enzymes responsible for the digestion of dietary carbohydrates to glucose are α-glucosidase and α-amylase. One of the most well-known properties of polyphenols especially phenolic acids on carbohydrate metabolism is the inhibition of these enzymes. Some investigations have shown that polyphenols are also able to regulate postprandial glycemia and inhibit the development of glucose intolerance by a facilitated insulin response and increased secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike polypeptide-1 (GLP-1). In addition, polyphenols are able to regulate the key pathways involved in carbohydrate metabolism and hepatic glucose homeostasis. These include glycolysis, glycogenesis and gluconeogenesis, which are usually impaired in diabetes. The current study focuses on the glucose-controlling properties of phenolic compounds extracted from oil palm (Elaeis guineensis), a high oil-producing tropical plant that also rich in phytochemicals. The major phenolic components in OPP are identified as caffeoylshikimic acid, protocatechuic acid and p-hydroxybenzoic acid. OPP has been found to exert various positive health effects parallel to the well-established physiological benefits of polyphenols. It has been shown that OPP protects against early type 2 diabetes and encouraging results suggest its role in modulating the development of diabetes. The current study aims to investigate and determine the effects of oil palm phenolics (OPP) on the blood glucose control in pre-diabetics.

Official Title
-----------------
Modulating Effects of Oil Palm Phenolics in Subjects With Pre-diabetes

Conditions
-----------------
Prediabetes

Intervention / Treatment
-----------------
* Dietary Supplement: Oil Palm Phenolics
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject with pre-diabetes, i.e. fasting plasma glucose level of more than 5.6 mmol/L and less than 7.0 mmol/L; or 2-hr plasma glucose load level of more than 7.8 mmol/L and less than 11.0 mmol/L. Subjects or his/her legally acceptable representative is willing to provide written informed consent. Exclusion Criteria: Subject with terminal cancer. Subject with renal failure (serum creatinine more than 200 umol/L). Subject with significant liver impairment (liver function test of 5 times more than the upper limit level). Subject with severe dementia and psychosis. Subject requires of long term corticosteroid treatment for the underlying disease such as connective tissue disorder. Subject with hemoglobinopathy or anemia. Subject underwent splenectomy or suffered from splenomegaly. Subject with pre-existing cardiovascular disease. Subject with chronic substance abuse such as chronic alcoholism or chronic opiate usage. Female subject of childbearing potential unless subject underwent bilateral tubal ligation, bilateral oophorectomy or hysterectomy previously. Subject with other significant uncontrolled medical illnesses that may interfere with drug administration or interpretation of results. Subject who have been included in any other clinical trial within the previous 3 months.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oil Palm Phenolics<br>500 mg gallic acid equivalent (GAE), twice daily, 12 months | Dietary Supplement: Oil Palm Phenolics<br>* Palm fruit derived phenolics compound<br>|
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Glucose Level | Serum Glycosylated Haemogoblin (<5.7% indicates healthy, 5.7% - 6.4% indicates prediabetes, >6.5% indicates diabetes) Plasma glucose level of oral glucose tolerance test (<7.8 mmol/L indicates healthy, 7.8 mmol/L - 11 mmol/L indicates prediabetes, >11 mmol/L indicates diabetes) Fasting plasma glucose level (<5.6 mmol/L indicates healthy, 5.6 mmol/L - 6.9 mmol/L indicates prediabetes, >6.9 mmol/L indicates diabetes) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | Model-derived Oral Glucose Insulin Sensitivity (OGIS) Index will be calculated using weight (kg), height (cm), glucose (mmol/L) and insulin (pmol/L). | 12 months | 
| Lipid profile | Total cholesterol, Low-density lipoprotein, High-density lipoprotein, Triglycerides | 12 months | 
| Global Assessment of Efficacy | Very good, good, no change, unsatisfactory and very unsatisfactory | 12 months | 
| Beta Cell Function | Homeostatic Model Assessment (HOMA2-B) to determine beta cell function | 12 months |