Clinical trial NCT01363141: Effect of a Low Advanced Glycation End Products (AGE) Diet in the Metabolic Syndrome
Official title: Effects of Glycooxidative Stress on Human Aging- Study #3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Keywords: Cardiovascular Diseases
Type 2 Diabetes Mellitus
Abdominal Fat
Atherogenic Dyslipidemia
Hypertension
Hyperglycemia
Insulin Resistance
Thrombosis state
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2011-06-01
Enrollment: 383
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Blood Glucose and Insulin levels in 1 year as compared to baseline
timeFrame: baseline
measure: Change in Blood Glucose and Insulin levels in 1 year as compared to baseline
timeFrame: after 1 year
Secondary outcomes:
measure: Change in abdominal obesity in 1 year as compared to baseline
timeFrame: baseline
measure: Change in abdominal obesity in 1 year as compared to baseline
timeFrame: after 1 year
measure: Change in markers of cardiovascular disease in 1 year as compared to baseline
timeFrame: baseline
measure: Change in markers of cardiovascular disease in 1 year as compared to baseline
timeFrame: after 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: John C He, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12. doi: 10.1016/j.jada.2010.03.018.
citation: Mericq V, Piccardo C, Cai W, Chen X, Zhu L, Striker GE, Vlassara H, Uribarri J. Maternally transmitted and food-derived glycotoxins: a factor preconditioning the young to diabetes? Diabetes Care. 2010 Oct;33(10):2232-7. doi: 10.2337/dc10-1058. Epub 2010 Jul 13.
citation: Uribarri J, Cai W, Ramdas M, Goodman S, Pyzik R, Chen X, Zhu L, Striker GE, Vlassara H. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care. 2011 Jul;34(7):1610-6. doi: 10.2337/dc11-0091.
citation: Vlassara H, Striker GE. Advanced glycation endproducts in diabetes and diabetic complications. Endocrinol Metab Clin North Am. 2013 Dec;42(4):697-719. doi: 10.1016/j.ecl.2013.07.005.
citation: Striker GE. Beyond phosphate binding: the effect of binder therapy on novel biomarkers may have clinical implications for the management of chronic kidney disease patients. Kidney Int Suppl. 2009 Dec;(114):S1-2. doi: 10.1038/ki.2009.400. No abstract available.
citation: 6. Vlassara, H. and Striker, G.E. (2010) Intake of advanced glycation endproducts; Role in the development of diabetic complications. In: Principles of Diabetes Mellitus, 2nd Edition, L. Poretsky, Ed., Springer Publications.
citation: 7. Vlassara, H, Striker, G.E. The Role of AGEs in the Etiology of Insulin Resistance and Diabetes; US-Endocrinology (2011).
citation: Vlassara H, Cai W, Tripp E, Pyzik R, Yee K, Goldberg L, Tansman L, Chen X, Mani V, Fayad ZA, Nadkarni GN, Striker GE, He JC, Uribarri J. Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial. Diabetologia. 2016 Oct;59(10):2181-92. doi: 10.1007/s00125-016-4053-x. Epub 2016 Jul 29.