Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes

Not Applicable

Completed

Conditions: Type 2 Diabetes

Registration Number: NCT03944616

Lead Sponsor: University of California, Irvine

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 181

Inclusion Criteria

Not provided

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
HbA1c	Time 0 (directly after 2-week run-in), 12, 24 weeks	Glycated hemoglobin

Secondary Outcome Measures

Name	Time	Method
Time In Range	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)	Time in range is collected by a masked Continuous Glucose Monitor (CGM), which measures individual glucose levels every 15 minutes for two weeks via a sensor placed on the participants upper arm (underside). Time in Range is defined as the % of time each day with a glucose measure between 70-180 mg/dl. The range of CGM data for inclusion in this study will be 5 to 14 days, consistent with manufacturer's recommendations.
Glycemic Variability	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)	Glycemic variability is collected by a masked Continuous Glucose Monitor (CGM), which measures individual glucose levels every 15 minutes for two weeks via a sensor placed on the participants upper arm (underside). Glycemic variability is defined as the Standard Deviation (SD) of the mean glucose during the wear period. The range of CGM data for inclusion in this study will be 5 to 14 days, consistent with manufacturer's recommendations.
Mean Glucose (mg/dl)	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)	A measure of the mean, 24 hour glucose concentration calculated across all recorded glucose readings during the wear period
Fasting Glucose	Time 0 (directly after 2-week run-in), 12, 24 weeks	Standard (mg/dl) measure taken fasting (morning) during baseline, 12 weeks, 24 weeks
Fasting Insulin (Pmol/L)	Time 0 (directly after 2-week run-in), week 12, week 24	Standard lab measurement for fasting insulin assessment
Fructosamine	Time 0 (directly after 2-week run-in),12, 24 weeks	Fructosamine (umol/L) represents usual glycemia over the past 2-3 weeks, and is considered a valid marker of short term clinical glycemic patterns by the American Diabetes Association
Weight (kg)	Time 0 (directly after 2-week run-in), 12, 24 weeks	Weight measured on standardized scale in gown
Total Cholesterol (mg/dL)	Time 0 (directly after 2-week run-in), 12, 24 weeks	Total cholesterol was measured as part of a lipid panel, a standard measurement for assessing clinical CVD risk
Kidney Function	Time 0 (directly after 2-week run-in),12, 24 weeks	eGFR-Cystatin-C (estimated glomerular filtration rate) = mL/min/1.73 m\^2
Systolic Blood Pressure	Time 0 (directly after 2-week run-in),12, 24 weeks	Systolic blood pressure (mmHg)
Diastolic Blood Pressure	Time 0 (directly after 2-week run-in), 12, 24 weeks	Standard part of blood pressure measurement (mmHG)
Apolipoprotein-AI	Time 0 (directly after 2-week run-in), 12, 24 weeks	Apo-AI the major protein component of high density lipoprotein (HDL)
Apolipoprotein B	Time 0 (directly after 2-week run-in), 12, 24 weeks	ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content
Fibrinogen (mg/dL)	Time 0 (directly after 2-week run-in), 12, 24 weeks	A protein involved in forming blood clots in the body
C-reactive Protein	Time 0 (directly after 2-week run-in), 12, 24 weeks	biomarker of inflammation
Aspartate Aminotransferase (AST) (U/L)	Time 0 (directly after 2-week run-in), 12, 24 weeks	AST (aspartate aminotransferase) is an enzyme that reflects liver function
Aminotransferase (ALT) (U/L)	Time 0 (directly after 2-week run-in), 12, 24 weeks	ALT (alanine transaminase) is an enzyme, a protein that reflects liver function
Alkaline Phosphatase (ALKPhos ) (U/L)	Time 0 (directly after 2-week run-in), 12, 24 weeks	ALP is an enzyme, a protein, that reflects liver function
Thyroid Stimulating Hormone (TSH)	Time 0 (directly after 2-week run-in), 12, 24 weeks	Hormone measured in the blood with energy balance related role
The Pittsburgh Sleep Quality Index (PSQI)	Time 0 (directly after 2-week run-in), 12, 24 weeks	The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality over a one-month time interval. Each component score of the PSQI ranges from 0 to 3, with 3 indicating the greatest dysfunction or disturbance. The seven component scores are then summed to obtain a global PSQI score, which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties
Dietary Quality (Healthy Eating Index -HEI)	Run-in period (2 weeks) - baseline, Week 1-12 (period 1), Week 13-24 (period 2).	The Healthy Eating Index (HEI) is a measure of diet quality used to assess how well a set of foods aligns with key recommendations and dietary patterns published in the Dietary Guidelines for Americans (Dietary Guidelines). The overall HEI scores are made up of 13 components that reflect the different food groups and key recommendations in the Dietary Guidelines for Americans. The HEI is scored 0-100 (low to high), with higher scores representing greater reported intake of an overall dietary pattern aligning with USDA Dietary Guidelines. In the SODAS study, dietary intake was assessed by multiple unannounced 24-hour dietary recalls that occurred during the 2-week run-in period to assess usual habits (2 recalls over 2 weeks) and the active intervention (5 recalls over 24 weeks: 2 to 3 recalls during weeks 1-12 (period 1), and 2 to 3 recalls during weeks 13-24 (period 2). to measure any changes in diet quality. Scores during each period represent the average score of recalls.
The Diabetes Health Profile (DHP-18)	Time 0 (directly after 2-week run-in), 12, 24 weeks	The Diabetes Health Profile (DHP-18) is used to assess health related quality of life in diabetes across three domains (psychological distress, barriers to activity and disinhibited eating). Each item is scored on a 4-point scale, and the subscale scores are then rescaled to a 0-100 range, with higher scores indicating poorer well-being.
Food Craving Inventory (FCI)	Time 0 (directly after 2-week run-in), 12, 24 weeks	The FCI is a valid and reliable self-report measure of specific food cravings. The inventory consists of 4 factors or subscales measuring cravings for high fats (8 items), carbohydrates/starches (8 items), sweets (8 items), and fast food fats (4 items), and a total score is calculated by summing the subscales. Participants rate each food on a 5-point Likert scale ranging from 0 (never) to 4 (always/almost every day). We calculated the total score by summing the individual item responses in each subscale. Higher scores indicate more frequent cravings of the 28 items.
Medication Effect Score (MES)	Time 0 (directly after 2-week run-in), 6, 12, 18, 24 weeks	The medication effect score (MES) is a measure of overall diabetes regimen intensity, and is based on the dosages of medications used and their potencies. The MES is calculated for each diabetes medication in a regimen using the following equation: (actual drug dose/maximum drug dose) × drug-specific adjustment factor. The adjustment factor equates to the expected decrease in HbA1c achieved by the drug as monotherapy. The MES presumes a linear relationship between medication dosage and HbA1c, and the sum of MES values attributed to individual medications represents the maximum A1c reduction that may be expected by the regimen. It is a continuous variable with range 0 (no medications), and the maximum achievable MES is patient specific and dependent on the total number of and dose of medications reported.
Therapeutic Intensity Score (TIS)	Time 0 (directly after 2-week run-in), 6, 12, 18, 24 weeks	The therapeutic intensity score (TIS) is a summary measure that accounts for the number of medications and the relative doses a patient received to lower blood pressure. It is a continuous variable with range 0 (no medications), and the maximum achievable TIS is patient specific and dependent on the total number of antihypertensive medications reported.

Trial Locations

Locations (2): University of California, Irvine
🇺🇸
Irvine, California, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
University of California, Irvine
🇺🇸Irvine, California, United States