Effect of a Low Advanced Glycation End Products (AGE) Diet in the Metabolic Syndrome

Study Overview
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Brief Summary
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The investigators have previously demonstrated that Advanced Glycation End products (AGEs) are associated with several chronic diseases in humans and that blood AGE levels can be significantly reduced by simply changing the way food is cooked. This is an interventional-randomized study in which we are trying to determine whether a diet low in AGE followed for 1 year can effectively reduce circulating AGE levels as well as markers of the metabolic syndrome in a group of patients with these abnormal markers.

Detailed Description
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The metabolic syndrome (MetSyn), a well-defined cluster of pathogenic conditions, includes glucose intolerance, insulin resistance (pre-diabetes), hypertension, abdominal obesity, and dyslipidemia. The MetSyn has a strong inflammatory component and raises the risk for cardiovascular disease (CVD) by five-fold and of diabetes by two fold in aging. Although, excessive caloric intake, i.e. over nutrition is known to be involved in developing the MetSyn, the actual causative agents of MetSyn in human nutrition have not been determined. The investigators have previously shown that Advanced Glycation End products (AGEs) can induce oxidant stress and inflammatory responses and modulate insulin signaling in animal models and more recently in humans. These studies separated the effects of over-nutrition from the pro-inflammatory effects of AGEs, a factor not previously considered. These data support our hypothesis that AGE-restriction could be an important intervention in the MetSyn in aging. The investigators would like to demonstrate that this safe, practical and economical intervention can arrest the progression of three major epidemics of aging: diabetes, obesity, and vascular disease associated with the metabolic syndrome. This simple intervention could have significant health and economic implications. Our hypothesis is that dietary AGE restriction can reverse several cardinal manifestation of the MetSyn, specifically insulin resistance, abdominal obesity and cardiovascular disease.

Official Title
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Effects of Glycooxidative Stress on Human Aging- Study #3

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Other: Regular AGE Diet
* Other: Low AGE Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking adult subjects with at least three of the following five characteristics of the metabolic syndrome (MetSyn): Waist circumference: Men: > 102 cm Women: > 88 cm Blood pressure: > 130/85 mm Hg (or use of anti-Blood Pressure medication) HDL-cholesterol: Men: < 40 mg/dL Women: < 50 mg/dL Triglycerides: > 150 mg/dL (or use of medications for high triglycerides such as fibrates or nicotinic acid) Fasting blood sugar > 100 mg/dl (or use of metformin), but a Glycated hemoglobin (HbA1c) <6.5% Any gender and race 50 years old or above Dietary AGE intake > 12 AGE Eq/day (Before randomization all participants will be screened with a 3-day food record and 7-day food frequency questionnaire (AGE Quick Score) to determine their average spontaneous daily intake of AGEs. Only those subjects whose daily intake is > 12 AGE Eq/day will participate in the study.) Exclusion Criteria: Diagnosis of diabetes (HbA1C > 6.5 %) Glomerular Filtration Rate (GFR) less than 60 ml/min Any major cardiovascular event within the preceding 3 months Inability to understand or unwillingness to follow study diets Any unstable medical condition requiring medication adjustment or treatment within the preceding 3 months Any severe illness with an expected participant survival less than 1 year Diagnosis of HIV Currently receiving treatment for any inflammatory condition Currently receiving cancer treatment, such as radiation, chemotherapy, hormone therapy, or stem cell transplant Currently participating in any other research study requiring a special diet, medications, supplements or other lifestyle change

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Regular AGE Diet<br>Regular AGE Diet | Other: Regular AGE Diet<br>* Regular AGE Diet<br>|
| Active Comparator: Low AGE Diet<br>One year reduction in dietary AGE intake | Other: Low AGE Diet<br>* One year reduction in dietary AGE intake.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Glucose and Insulin levels in 1 year as compared to baseline | To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve insulin resistance in subjects with metabolic syndrome. Insulin resistance will be assessed by measuring simultaneously blood glucose and insulin levels in the fasting state and during an oral glucose tolerance test. | baseline | 
| Change in Blood Glucose and Insulin levels in 1 year as compared to baseline | To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve insulin resistance in subjects with metabolic syndrome. Insulin resistance will be assessed by measuring simultaneously blood glucose and insulin levels in the fasting state and during an oral glucose tolerance test. | after 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in abdominal obesity in 1 year as compared to baseline | To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness. | baseline | 
| Change in abdominal obesity in 1 year as compared to baseline | To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness. | after 1 year | 
| Change in markers of cardiovascular disease in 1 year as compared to baseline | To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness. | baseline | 
| Change in markers of cardiovascular disease in 1 year as compared to baseline | To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness. | after 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular Diseases, Type 2 Diabetes Mellitus, Abdominal Fat, Atherogenic Dyslipidemia, Hypertension, Hyperglycemia, Insulin Resistance, Thrombosis state