Effect of Whole Grain Diet on Insulin Sensitivity, Advanced Glycation End Products and Inflammatory Markers in Pre-diabetes

Study Overview
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Brief Summary
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Food products derived from cereal grains constitute a major part of the daily diet of many Americans . For example, a typical Chinese American eats rice about 9.5 times a week on an average. However, most of these foods are derived from refined grain. During the refining process grains are stripped of their bran and germ which results in depletion of several biologically active constituents including fiber, anti-oxidants, phytoestrogens and minerals. From observational studies there is evidence for a protective effect of whole-grain foods with regard to the development of type 2 diabetes. More recently, higher intake of whole grains was also associated with decreases in insulin resistance - a risk factor related to the development of type 2 diabetes. In this randomized study the investigators plan to replicate this beneficial effect of improving insulin sensitivity in patients with pre-diabetes and go a step further by exploring the potential mechanisms by which this benefit may occur. The investigators will assess the effect of consuming a whole-grain-rich diet on levels of advanced glycation endproducts (AGE), RAGE (receptor for AGE) and markers of inflammation and oxidative stress - all of which have been shown to play an important role in the pathogenesis of diabetes mellitus. The investigators will also look for correlations between the levels of these markers with insulin sensitivity to identify potential mechanisms of pathogenesis.

Official Title
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Effect of Whole Grain Diet on Insulin Sensitivity, Advanced Glycation End Products and Inflammatory Markers in Pre-diabetes

Conditions
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Diabetes, Prediabetes

Intervention / Treatment
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* Other: Whole grain rice
* Other: Refined grain rice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years to unlimited, both genders. At least one meal per day included rice in the seven days prior to enrolment. No current diagnosis of Diabetes Mellitus (DM). Fasting blood glucose value between 100 to 125 mg/dl and/or Hemoglobin A1c levels between 5.7%-6.4%. ≥ 2 visits with primary care physician to establish compliance Exclusion Criteria: Special diets (e.g. vegetarian) Use of medications that would affect blood sugar levels (e.g. steroids) Allergy to any type of grain Body weight fluctuation over the past 180 days of ≥ 10% Planning to significantly change level of physical activity during the time of study. Planning to move out of town or take a vacation for ≥ 14 days during the time of the study Current smoker Consumption of greater than 2 alcoholic drinks per day History of malignancy and overt cardiovascular disease (apart from hypertension).

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole grain rice<br> | Other: Whole grain rice<br>* Whole grain rice arm (treatment arm): Subjects will be provided a supply of whole grain rice and will be asked to prepare rice items in their meal with the provided whole grain rice while participating in the study<br>|
| Active Comparator: Refined grain rice<br> | Other: Refined grain rice<br>* Refined grain rice arm (control arm): Subjects will be provided a supply of refined grain rice and will be asked to prepare rice items in their meal with the provided refined grain rice while participating in the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Homeostatic Model Assessment (HOMA) Index | Estimates insulin resistance and β-cell function from fasting glucose and insulin levels | 0 | 
| Homeostatic model assessment(HOMA) index | Estimates insulin resistance and β-cell function from fasting glucose and insulin levels | 6 weeks | 
| Homeostatic model assessment (HOMA) index. | Estimates insulin resistance and β-cell function from fasting glucose and insulin levels | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carboxymethyl lysine (CML) | Advanced glycation end product (in blood and urine) | 0, 6 and 12 weeks | 
| Methylglyoxal (MG) | Advanced glycation end product (in blood and urine) | 0, 6 and 12 weeks | 
| IL-6 | Inflammatory marker | 0, 6 and 12 weeks | 
| Receptor for advanced glycation endproducts (RAGE) | Receptor for advanced glycation endproducts | 0, 6 and 12 weeks | 
| Sirtuin 1 | A protein that in humans is encoded by the SIRT1 gene and regulates processes such as apoptosis and muscle differentiation by deacetylating key proteins. It is down regulated in cells that have high insulin resistance and inducing its expression increases insulin sensitivity | 0, 6 and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Prediabetes, Prevention, Whole grain, Advanced glycation end products, Insulin sensitivity