Saccharin and Acesulfame Potassium Consumption and Glucose Homeostasis in Older Adults With Prediabetes

Insulin Sensitivity Clinical Trial

Official title:

Saccharin and Acesulfame Potassium Consumption and Glucose Homeostasis in Older Adults With Prediabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05441982
• Other study ID #: 1R21AG080358-01
• Status: Recruiting
• Phase: N/A
• Start date: September 21, 2023
• Est. completion date: December 2025

Study information

• Verified date: December 2023
• Source: Virginia Polytechnic Institute and State University
• Contact: Valisa Hedrick, PhD
• Phone: 540-231-7983
• Email: vhedrick[@]vt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 saccharin, but not acesulfame potassium, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS.

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., two commonly consumed NNS, saccharin and acesulfame potassium). 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 saccharin, but not acesulfame potassium, 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 saccharin intake influences glucose homeostasis. Following a 2-week eucaloric lead-in diet, 51 middle-aged/older adults (40+ yrs) with prediabetes will be randomly assigned to 1 of 3 controlled feeding conditions for 6 weeks (17 participants per group): saccharin, acesulfame potassium, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 51
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Age 40+ 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

Related Conditions & MeSH terms

• Continuous Glucose Monitoring
• Inflammatory Markers
• Insulin Resistance
• Insulin Sensitivity
• Oral Glucose Tolerance
• Prediabetic State

Intervention

Other:
• Non-Nutritive Sweetener Intake and impact on glucose homeostasis
Provision of either saccharin, acesulfame potassium, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.

Locations

Country	Name	City	State
United States	Virginia Tech	Blacksburg	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Polytechnic Institute and State University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Insulin Sensitivity	Insulin uU/mL concentrations from the oral glucose tolerance test at baseline and follow-up will be used	6 weeks
Secondary	Serum Endotoxin	Serum endotoxin mg/L concentrations will be measured at baseline and follow-up	6 weeks
Secondary	C-reactive protein	C-reactive protein mg/dL concentrations will be measured at baseline and follow-up	6 weeks
Secondary	Tumor Necrosis Factor alpha	Inflammatory cytokine: Tumor Necrosis Factor alpha pg/mL concentrations will be measured at baseline and follow-up	6 weeks
Secondary	Interleukin 6	Inflammatory cytokine: Interleukin 6 pg/mL concentrations will be measured at baseline and follow-up	6 weeks
Secondary	Monocyte chemoattractant protein-1	Inflammatory cytokine: Monocyte chemoattractant protein-1 pg/mL concentrations will be measured at baseline and follow-up	6 weeks