Restriction of Dietary AGEs to Prevent Diabetes in Overweight Individuals

Sponsor
Maastricht University Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT03866343
Collaborator
(none)
82
1
2
29.8
2.7

Study Details

Study Description

Brief Summary

Current efforts to arrest the epidemic of type 2 diabetes mellitus (T2DM) have had limited success. Thus there is an urgent need for effective approaches to prevent the development of T2DM. It is widely accepted that the current epidemic is driven by an increase in global food abundance and reduced food quality, making changes in diet a key determinant of the T2DM epidemic. Dietary factors can affect cardio-metabolic health; among these factors, advanced glycation end-products (AGEs) in food are potential risk factors for insulin resistance and T2DM.

AGEs are a heterogeneous group of unavoidable stable bioactive compounds. Endogenous formation of AGEs is a continuous naturally occurring process, and is the result of normal metabolism. However, increased formation of AGEs occurs during ageing and under hyperglycaemic conditions. AGEs are implicated in the development of diabetes and vascular complications.

Over the past several decades, methods of food processing have changed and meals now contain excess fat and sugar and are most susceptible for the formation of AGEs. In addition, AGEs in food are highly desirable due to their profound effect on shelf life, sterility, flavour, colour, and thus food consumption. Hence, a substantial portion of AGEs are derived from exogenous sources, particularly food. These exogenous AGEs are potential risk factors for insulin resistance and the development of T2DM. The investigators recently found that dietary AGEs represent a significant source of circulating AGEs, and have similar pathogenic properties compared to their endogenous counterparts including the development of insulin resistance and T2DM. Taken together, dietary AGEs are proposed to play a pivotal role in the development and progression of T2DM and its complications. Reduction of dietary intake of AGEs may therefore be an alternative strategy to reduce the risk of vascular disease and insulin resistance. The investigators therefore hypothesize that dietary restriction of AGEs in overweight individuals improves insulin sensitivity, β-cell function, and vascular function.

Condition or Disease Intervention/Treatment Phase
  • Other: Diet low or high in advanced glycation endproducts
N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
82 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Restriction of Dietary AGEs to Prevent Diabetes in Overweight Individuals: a Randomized Controlled Trial
Actual Study Start Date :
Sep 7, 2018
Actual Primary Completion Date :
Mar 3, 2021
Actual Study Completion Date :
Mar 3, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Low AGE diet

Subjects will be asked to consume a diet containing a low AGE content for 4 weeks.

Other: Diet low or high in advanced glycation endproducts
All subjects will undergo an intervention consisting of a prescribed diet containing either a low or high quantity of AGEs during 4 continuous weeks.

Other: High AGE diet

Subjects will be asked to consume a diet containing a high AGE content for 4 weeks.

Other: Diet low or high in advanced glycation endproducts
All subjects will undergo an intervention consisting of a prescribed diet containing either a low or high quantity of AGEs during 4 continuous weeks.

Outcome Measures

Primary Outcome Measures

  1. Insulin sensitivity [Difference after 4 weeks of intervention]

    Assessed by hyperinsulinaemic-euglycaemic clamp

Secondary Outcome Measures

  1. Microvascular function [Difference after 4 weeks of intervention]

    Assessed by contrast-enhanced ultrasound (CEUS) in skeletal muscle

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Abdominal obesity: waist circumference for men ≥ 102 cm, and for women ≥ 88 cm.

  • Aged 18 years and older

  • Caucasian (because of skin fluorescence and capillary microscopy measurements)

Exclusion Criteria:
  • Diabetes (i.e. using anti-diabetic medication, fasting glucose >7.0 mmol/L, HbA1c

6.5%).

  • Active or history of cardiovascular disease (e.g. stroke, coronary artery disease, peripheral vascular disease, congestive heart failure, cardiac shunts, cardiac surgery, pulmonary hypertension, cardiac arrhythmias, family history of cardiac arrhythmias or sudden cardiac death)

  • Hyperlipidemia (defined as serum total cholesterol > 8 mmol/L or TG > 4 mmol/L)

  • Lipid lowering medication (e.g. statins)

  • Use of medication known to influence glucose metabolism, vascular function and/or lipid metabolism (e.g. statins, glucocorticosteroids, NSAID's)

  • Inability to stop antihypertensive medication for 13 weeks. Exclusion of higher grade hypertension (> 179 mmHg SBP and/or > 109 mmHg DBP) in order not to expose subjects to unnecessary risks)

  • Pulmonary or inflammatory disease

  • Kidney failure or electrolyte disorders

  • Pregnancy or lactation

  • No change in use of oral anticonceptiva or IUD (12 weeks prior of during the intervention)

  • Known allergic reaction to ultrasound contrast-agent

  • Smoking (active or cessation <1 year prior to screening date).

  • High alcohol usage (>4 U/day) or drug abuse

  • Use of dietary supplements or an investigation product within the previous month

  • Significant food allergies/intolerance

  • Vegetarianism

  • Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the intervention.

  • Participation in another biomedical trial during the past 30 days.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Maastricht University Maastricht Limburg Netherlands 6226

Sponsors and Collaborators

  • Maastricht University Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT03866343
Other Study ID Numbers:
  • NL63215.068.17
First Posted:
Mar 7, 2019
Last Update Posted:
Mar 8, 2021
Last Verified:
Mar 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 8, 2021