Non-Nutritive Sweetener Consumption and Glucose Homeostasis in Older Adults With Prediabetes

Non-Nutritive Sweetener Consumption (Aspartame and Sucralose) and Glucose Homeostasis in Older Adults With Prediabetes

Animal and observational research in humans suggest that specific types of non-nutritive sweeteners (NNS) may impair glycemic control. However, whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS.

Study Overview

• Status: Recruiting
• Conditions: Insulin Sensitivity; Inflammatory Markers; Continuous Glucose Monitoring; Oral Glucose Tolerance
• Intervention / Treatment: Other: Non-Nutritive Sweetener Intake and impact on glucose homeostasis

Detailed Description

Observational research has linked intake of non-nutritive sweeteners (NNS), which are consumed daily by ~50% of middle-aged/older U.S. adults, with increased risk of type 2 diabetes (T2D). This risk may be exacerbated by advancing age, which is associated with low-grade chronic inflammation and increased risk of T2D. Current T2D prevention recommendations related to NNS usage are unclear and confusing; use as an alternative to added sugar intake is suggested but long-term NNS use is discouraged despite minimal research to support this recommendation. Animal and observational human studies suggest detrimental effects of some NNS on glucose homeostasis. Longer-term human studies largely demonstrate null findings. Differences in study design and a lack of rigor in existing research contribute to inconclusive findings. In addition, NNS are often studied as a single entity yet types of NNS vary in their absorption and metabolism (e.g., the two most commonly consumed NNS, sucralose and aspartame). Whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS. We will investigate changes in inflammatory markers as potential mechanisms by which sucralose intake influences glucose homeostasis. Following a 2-week eucaloric lead-in diet, 51 middle-aged/older adults (50+ yrs) with prediabetes will be randomly assigned to 1 of 3 controlled feeding conditions for 6 weeks (17 participants per group): sucralose, aspartame, or a control group (no NNS). Standardized diets will be matched for macronutrients (50% carbohydrate, 35% fat, 15% protein) and other variables to avoid the potential confounds of weight change and dietary factors which may influence study outcomes (e.g., added sugars). All groups will receive identical diets, other than the additional NNS for the two NNS groups. 24-hr glycemic control using continuous glucose monitoring and insulin sensitivity and beta cell function via oral glucose tolerance test (OGTT), serum endotoxin, and inflammatory cytokines, including C-reactive protein, will be measured before and following the 6-week dietary treatment period. This research may have clinical practice and policy implications by informing U.S. dietary guidelines and guidelines for T2D prevention, which devote minimal attention to NNS and provide unclear guidance on NNS use due largely to a lack of rigorously-designed controlled feeding trials.

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elaina Marinik, PhD; Phone Number: 540-231-0923; Email: emarinik@vt.edu
• Study Contact Backup: Name: Valisa Hedrick, PhD; Phone Number: 540-231-7983; Email: vhedrick@vt.edu

Study Locations

• United States
  • Virginia
    • Blacksburg, Virginia, United States, 24061
      • Recruiting
      • Virginia Tech
      • Contact: Valisa Hedrick, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 50+ years
• Prediabetic (fasting glucose concentration of 100-125 mg/dL, 2-hour oral glucose tolerance test glucose concentration of 140-199 mg/dL, or a HbA1c value of 5.7% to 6.4%)
• Weight stable for previous 6 months (±2 kg)
• BMI <40 kg/m2
• Sedentary to recreationally active
• No plans to gain/lose weight or change physical activity level
• Willing to pick up food daily and consume foods provided for an 8-week period
• Verbal and written informed consent
• Approval by Medical Director
• Consume less than one serving of non-nutritive sweetener per week

Exclusion Criteria:

• BMI >40 kg/m2
• Diabetes or diabetes medication
• Antibiotic, prebiotic or prebiotic use in prior 3 months
• Uncontrolled hypertension (blood pressure (BP) > 159/99 mmHg)
• Diagnosed inflammatory bowel disease
• Past or current heart diseases, stroke, respiratory disease, endocrine or metabolic disease, or hematological-oncological disease
• Vegetarian or vegan
• Pregnant or plans to become pregnant
• Breastfeeding
• Food allergies or aversions, Phenylketonuria (PKU)
• Estrogen or testosterone usage

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspartame; Controlled feeding study. Dosage of aspartame will follow 50% of the acceptable daily intake (equivalent to 25 mg/kg for aspartame). This amount represents 1,500 mg/day of aspartame for a 60 kg adult.	Other: Non-Nutritive Sweetener Intake and impact on glucose homeostasis; Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.
Active Comparator: Sucralose; Controlled feeding study. Dosage of sucralose will follow 50% of the acceptable daily intake (equivalent to 2.5 mg/kg for sucralose). This amount represents 150 mg/day of sucralose for a 60 kg adult.	Other: Non-Nutritive Sweetener Intake and impact on glucose homeostasis; Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.
Sham Comparator: No NNS; Controlled feeding study with no non-nutritive sweeteners.	Other: Non-Nutritive Sweetener Intake and impact on glucose homeostasis; Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour glycemic control	The area under the curve (AUC) glucose concentrations, mg/dl from the continuous glucose monitoring at baseline and follow-up will be used	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral glucose tolerance	Oral glucose tolerance in response to 75 g glucose load; levels of glucose mg/dl will be determined 2 hrs after consuming a 75 glucose load	6 weeks
Insulin Sensitivity	Insulin uU/mL concentrations from the oral glucose tolerance test at baseline and follow-up will be used	6 weeks
Serum Endotoxin	Serum endotoxin mg/L concentrations will be measured at baseline and follow-up	6 weeks
C-reactive protein	C-reactive protein mg/dL concentrations will be measured at baseline and follow-up	6 weeks
Tumor Necrosis Factor alpha	Inflammatory cytokine: Tumor Necrosis Factor alpha pg/mL concentrations will be measured at baseline and follow-up	6 weeks
Interleukin 6	Inflammatory cytokine: Interleukin 6 pg/mL concentrations will be measured at baseline and follow-up	6 weeks
Monocyte chemoattractant protein-1	Inflammatory cytokine: Monocyte chemoattractant protein-1 pg/mL concentrations will be measured at baseline and follow-up	6 weeks

Collaborators and Investigators

• Sponsor: Virginia Polytechnic Institute and State University
• Investigators: Principal Investigator: Valisa Hedrick, PhD, Virginia Polytechnic Institute and State University

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2023
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Prediabetic State; Insulin Resistance
• Other Study ID Numbers: 1R21AG075344-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified study data will be posted to Virginia Tech's data repository, VTechData (https:// data.lib.vt.edu/). Datasets selected for sharing will be made accessible through VTechData, managed by the University Libraries at Virginia Tech. VTechData highlights, preserves, and provides access to data generated at Virginia Tech. The system relies on item/dataset level metadata as the primary building block to data discovery, access, and reuse. Published datasets are to be made accessible for at least five years.
• IPD Sharing Time Frame: Data will be available following completion of the trial and will be available for at least 5 years
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No