Cardiometabolic Effects of Non-Nutritive Sweeteners (NNS) in Type 1 Diabetes (T1D)

The purpose of this project is to learn how NNS affects the health of the blood vessels.

Type 1 diabetes (T1D) is an autoimmune disease that requires lifelong dependence on prescribed insulin. Scientists know that if an individual has T1D, they are at greater risk of having cardiovascular disease than people who do not have diabetes.

To help manage diabetes, individuals may talk with their doctor about adjusting what they normally eat or drink. Doctors typically ask that individuals avoid foods and drinks with lots of sugar in them. In response to this, individuals might drink diet drinks or eat snacks or other foods that are sugar-free. Sugar-free drinks and foods have NNS which help things taste sweet without impacting their blood glucose.

Concern exists that consuming NNS may make individuals more at risk for developing cardiovascular disease. Although the American Heart Association advises against long-term NNS consumption, about 20% of all beverages consumed by children contain NNS.

Currently, there are no scientifically backed questionnaires to assess how much NNS someone is consuming. As well, there are no commercially available lab tests to determine how much NNS is in someone's blood. This makes it difficult to draw associations or causal relationships between NNS exposure and health outcomes.

By conducting this project, the investigators hope to gain knowledge to potentially inform and revise care guidelines for individuals with T1D and ultimately lead to improved nutritional recommendations and clinical care of children.

• Cherry Sports Drink (Dietary supplement), also known as Gatorade Zero Glacier Cherry™: 12 oz bottle (1 1/2 cups) of Gatorade G Zero Glacier Cherry™ Sports Drink

Primary outcomes

• Change in "in vivo" endothelial function and vascular stiffness [2 years (duration of study)]: Brachial artery ultrasound will measure flow-mediated dilation % (FMD%) at baseline and 1 hour after drinking a non-nutritive sweetened sports drink.

Secondary outcomes

• Associations of circulating NNS levels with self-reported food frequency assessments [2 years (duration of study)]: A food frequency survey has been developed of the most common categories of NNS containing foods and beverages. Participants will complete the food frequency survey to select the frequency by which they consumed a given product and the most common serving size over the past month.
• Impact of chronic NNS dietary consumption on cardiovascular health [2 years (duration of study)]: Changes 1-hour after NNS consumption from baseline will be measured by carotid-femoral pulse wave velocity, baseline flow velocity, and hyperemic flow velocity
• Impact of chronic NNS dietary consumption on metabolic health [2 years (duration of study)]: Changes 1-hour after NNS consumption from baseline will be measured by blood lipids, blood glucose, and blood pressure
• Impact of chronic NNS dietary consumption of T1D specific glycemic control [2 years (duration of study)]: Changes 1-hour after NNS consumption from baseline will be measured by 14-day continuous glucose monitor (CGM) data and 14-day insulin data for total daily dose and % basal insulin

Sex: All, ages: 15 Years to 24 Years

Inclusion Criteria:

1. Aged 15-24 years
2. Clinical diagnosis of type 1 diabetes, requiring insulin therapy, of ≥ 1 to < 10 years duration.
3. Last available HbA1c ≤ 8.5% (obtained by chart review in Children's Wisconsin Diabetes Clinic patients or verbally by individuals not receiving diabetes care at Children's Wisconsin)
4. Current use of an FDA approved automated insulin delivery (AID) system
5. Willing to consume a 12 ounce Gatorade G Zero Glacier Cherry drink in less than 10 minutes
6. Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is < 18 years of age

Exclusion Criteria:

1. Any disease other than type 1 diabetes that affects glucose, sex steroid, or fat metabolism such as polycystic ovary syndrome or hypercortisolism
2. Any medication use that may affect glucose, sex steroid, or fat metabolism such as metformin or glucocorticoids
3. Half or full sibling already participating in this study
4. Known cardiovascular disease such as hypertension or atherosclerosis, and/or use of an anti-hypertensive medication
5. Known hyperlipidemia, defined as LDL ≥ 160 mg/dL, and/or use of lipid-lowering medication, such as statin therapy
6. Known renal disease or microalbuminuria, and/or use of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blockers (ARBs) for microalbuminuria
7. Known diabetic retinopathy or neuropathy
8. Raynaud's phenomenon or other vascular disease
9. Obesity and/or body habitus that precludes completion of the flow-mediated brachial ultrasound study (generally, BMI > 40 kg/m2 in adults) - this is at study team's discretion.
10. Pregnancy or lactation
11. Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.