Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes
- Conditions
- Type 2 Diabetes
- Interventions
- Behavioral: Diet BeverageBehavioral: Water
- 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
Not provided
- 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
- Arm && Interventions
Group Intervention Description Diet Beverage Diet Beverage Participants will receive and consume three daily servings (24 ounces) of a non-caloric commercial diet beverage of their choice sweetened with FDA approved artificial sweeteners. Water Water Participants will receive and consume three daily servings (24 ounces) of plain bottled/canned water in place of their usual commercial diet beverage. The water will be unflavored, unsweetened, non-caloric, and may be plain or sparkling. Participants randomized to consume water will be instructed to avoid intake of diet beverages.
- Primary Outcome Measures
Name Time Method HbA1c 0, 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 CV and SD. The range of CGM data for inclusion in this study will be 5 to 14 days, consistent with manufacturer's recommendations.
Lipid panel (Total cholesterol, LDL cholesterol, HDL cholesterol, Fasting Triglycerides), all mg/dL 0, 12, 24 weeks A lipid panel is a standard measurement for assessing clinical CVD risk
Sleep Quality and Patterns 0, 6, 12, 18, 24 weeks Pittsburgh Sleep Quality Index
Serotonin 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses Chemical and neurotransmitter measured in blood with myriad roles, including appetite and digestion
Neuropeptide Y 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses Peptide measured in the blood with satiety related role
Fibrinogen 0, 12, 24 weeks A protein involved in forming blood clots in the body
Lipid intensity therapy score 0, 6, 12, 18, 24 weeks Reflects guidelines on intensity of lipid therapy for CVD risk none, low, moderate, high intensity categories
Weight (kg) 0, 6, 12, 18, 24 weeks Weight measured on standardized scale in gown
Physical activity All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days) Objectively measured via Activpal
Leptin 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses Hormone measured in the blood with satiety related role
Thyroid Stimulating Hormone (TSH) 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses Hormone measured in the blood with energy balance related role
Gut Microbiome 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses Measured with kit: Self-collection and stabilization of microbial DNA from feces for gut microbiome profiling
Comprehensive metabolomics 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses Serum collection for comprehensive metabolomics analysis for integrative analysis with gut microbiome
Dietary Practices 0, 6, 12, 18, 24 weeks Short questionnaire assessing dietary behaviors related to meal frequency, timing, and eating away from home
Therapeutic Intensity Score (TIS) 0, 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.
Other CGM metrics All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days) Multiple metrics are able to be calculated by CGM. The primary secondary endpoint for CGM will be Time In Range. Reporting of any other CGM metrics will be prefaced with this statement and the residual CGM metrics will be analyzed and interpreted cautiously and conservatively. They include: Mean glucose, glycemic variability, and episodes of hypoglycemia/hyperglycemia.
Blood pressure 0, 6, 12, 18, 24 weeks Systolic and Diastolic blood pressure, standard clinical measurement
Dietary Quality (Healthy Eating Index) Run-in period (2 weeks), Active intervention (Up to 24 weeks). Assessed by multiple unannounced 24-hour dietary recalls that will occur during the run-in to assess usual habits (2 recalls over 2 weeks) and the active intervention (5 recalls over 24 weeks), to measure any changes in diet quality metric. Results will be used to calculate a metric of diet quality in the Healthy Eating Index that is based upon the USDA Dietary Guidelines.
DHP-18 0, 6, 12, 18, 24 weeks A diabetes-specific patient reported outcome measure developed to evaluate the health-related quality of life of people living with type 2 diabetes
Food Craving Inventory 0, 6, 12, 18, 24 weeks Measures different domains of general and specific food cravings
cholecystokinin (CCK) 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses Peptide measured in the blood with satiety related role
Liver function panel 0, 12, 24 weeks Tests that measure various functions of liver
Medication Effect Score (MES) 0, 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.
Kidney function 0, 6, 12, 18, 24 weeks Serum creatinine/cystatin-c are standard clinical measurements for kidney function
Fasting glucose and Insulin 0, 6, 12, 18, 24 weeks Standard clinical measures
Apolipoprotein-B 0, 12, 24 weeks ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content
Apolipoprotein AI (Apo-AI) 0, 12, 24 weeks Apo-AI the major protein component of high density lipoprotein (HDL)
C-reactive protein 0, 12, 24 weeks biomarker of inflammation
Fructosamine/Glycated Albumin 0, 6, 12, 18, 24 weeks Fructosamine and glycated albumin levels represent usual glycemia over the past 2-3 weeks, and are considered valid markers of short term clinical glycemic patterns by the American Diabetes Association
Trial Locations
- Locations (2)
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of California, Irvine
🇺🇸Irvine, California, United States