Clinical trial NCT03944616: Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes
Official title: Effect of Artificially Sweetened Beverages on Diabetes Control in Adults With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Keywords: Diet beverages
diet
diabetes control
artificial sweeteners
continuous glucose monitor
gut microbiome
metabolomics
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: University of Minnesota
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2019-05-09
Enrollment: 181
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is testing the effect of commercial diet beverage intake on diabetes control parameters in free-living adults with type 2 diabetes in a randomized, two arm parallel trial with a run-in period of 2-weeks and an active intervention period of 24-weeks. We will recruit 200 patients with type 2 diabetes who are usual consumers of commercial diet beverages and randomize them to receive and consume either: 1) A commercial diet beverage of choice (3 servings or 24 oz. daily); or 2) Unflavored bottled water of choice (sparkling or plain) (3 servings or 24 oz. daily).
Primary purpose: PREVENTION

Brief summary: Diet beverages sweetened with artificial sweeteners occupy a unique category in the food environment as they are a source of intensely sweet taste with no calories. Diet beverages are the single largest contributor to artificial sweetener intake in the U.S. diet, and people with diabetes are the highest consumers of diet beverages, tending to consume them as a replacement for dietary sources of sugar, especially in place of sugar-sweetened beverages. This behavior has been endorsed by dietetic and scientific organizations, and diet beverages are marketed as being synonymous with better health, suitable for weight loss, and thus advantageous for diabetes control. The underlying public health concern is that there are few data to support or refute the benefit or harm of habitual diet beverage consumption by people with diabetes; therefore randomized trials with relevant outcomes must be conducted because they would address many limitations of previous research and have major implications for dietary recommendations on diet beverage intake and primary and secondary prevention of chronic disease. To begin addressing this important scientific gap the investigators are testing the effect of diet beverage intake on diabetes control parameters in free-living adults with type 2 diabetes in a randomized, two arm parallel trial with a run-in period of 2-weeks and an active intervention period of 24-weeks. This study will recruit 200 patients with type 2 diabetes who are usual consumers of commercial diet beverages and randomize them to receive and consume either: 1) A commercial diet beverage of choice (3 servings or 24 oz. daily); or 2) Unflavored bottled water of choice (sparkling or plain) (3 servings or 24 oz. daily). The primary outcome will be a central measure of clinical diabetes control in glycated hemoglobin (HbA1c). The study will also measure the nature and magnitude of glycemic excursions via continuous glucose monitors, as well as clinical markers of cardiometabolic risk and kidney function. Lastly, investigators will measure plausible mechanisms whereby diet beverage intake may alter risk by assessing the effect of diet beverage intake on the functional composition of the gut microbiome via stool samples and comprehensive metabolomics, satiety hormones, as well as usual dietary intake, and upstream behavioral pathways which may inform dietary intake patterns.


Eligibility criteria: Inclusion criteria: We will include men, women and non-binary participants with T2D, age 35 years and older, able to provide informed consent, otherwise healthy, who meet the following criteria:

* Physician diagnosed type 2 diabetes ≥ 6 months prior to screening
* HbA1c 6.5-8.5% at participant screening
* Current treatment with lifestyle changes or stable diabetes-related medication levels for the past 3 months
* Willingness to provide consent to contact treating physician and physician agreement to refrain from changing diabetes-related medications during the trial (change defined as \> 2 fold change in dose of any 1 hyperglycemic agent or addition or subtraction of an agent)
* No physician-directed medication change for 3 months if prescribed medication for lipids or blood pressure
* Usual consumers of diet beverages (≥ 3 servings/ week (24 oz.) and the willingness to maintain fidelity of the intervention, and participate in all aspects of the intervention
* Not actively looking to make major lifestyle alterations during the study period with stable weight for 2 months (within 3%).

Exclusion Criteria:

* Type 1 diabetes or suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin)
* "Secondary" diabetes due to specific causes (e.g. monogenic syndromes, pancreatic surgery, and pancreatitis)
* Diabetic Ketoacidosis hospitalization within last 6 months
* Severe/major hypoglycemia in the last 3 months-severe/major hypoglycemia is defined as a hypoglycemic event in which patient requires assistance of another person to manage the episode
* Glucocorticoid use (prednisone 2.5 mg/d or more or its equivalent)
* History of intolerance or allergy to diet beverages or AS or phenylketonuria
* Any condition that is known to affect the validity of the glycemic measures (Hba1c)
* Major cardiovascular disease event or surgery within past 6 months
* Gastrointestinal disease
* Renal or liver disease
* Current treatment for cancer
* Those with major surgery planned or history of bariatric surgery
* Antibiotic treatment (\> 6 days) within past 6 months
* Currently pregnant (via self-report) or planning to become pregnant during study period; \<1 year postpartum and breast feeding
* Current participation in another interventional clinical trial
* Previous randomization in this study,
* Heavy alcohol consumption (on average \>2 drinks/day for women and \>3 drinks/day for men)
* Habitual consumer of SSB ≥ 1 serving / day (8 oz.)
* Does not drink diet beverages
* BMI \< 20.0 kg/m2

Primary outcomes:
measure: HbA1c
timeFrame: 0, 12, 24 weeks
Secondary outcomes:
measure: Time In Range
timeFrame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
measure: Glycemic Variability
timeFrame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
measure: Other CGM metrics
timeFrame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
measure: Lipid panel (Total cholesterol, LDL cholesterol, HDL cholesterol, Fasting Triglycerides), all mg/dL
timeFrame: 0, 12, 24 weeks
measure: Kidney function
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Fasting glucose and Insulin
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Fructosamine/Glycated Albumin
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Blood pressure
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Weight (kg)
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Dietary Quality (Healthy Eating Index)
timeFrame: Run-in period (2 weeks), Active intervention (Up to 24 weeks).
measure: DHP-18
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Food Craving Inventory
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Sleep Quality and Patterns
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Physical activity
timeFrame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
measure: Serotonin
timeFrame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
measure: Leptin
timeFrame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
measure: Thyroid Stimulating Hormone (TSH)
timeFrame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
measure: Neuropeptide Y
timeFrame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
measure: cholecystokinin (CCK)
timeFrame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
measure: Gut Microbiome
timeFrame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
measure: Comprehensive metabolomics
timeFrame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
measure: Dietary Practices
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Apolipoprotein-B
timeFrame: 0, 12, 24 weeks
measure: Apolipoprotein AI (Apo-AI)
timeFrame: 0, 12, 24 weeks
measure: Fibrinogen
timeFrame: 0, 12, 24 weeks
measure: C-reactive protein
timeFrame: 0, 12, 24 weeks
measure: Liver function panel
timeFrame: 0, 12, 24 weeks
measure: Medication Effect Score (MES)
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Therapeutic Intensity Score (TIS)
timeFrame: 0, 6, 12, 18, 24 weeks
measure: Lipid intensity therapy score
timeFrame: 0, 6, 12, 18, 24 weeks
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
References: