Carbohydrates Under Target for Type 1 Diabetes Management

Study Overview
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Brief Summary
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Recently there has been an increased interest in limiting intake of carbohydrates (CHO) for improving long term health. While healthcare professionals (HCPs) are sometimes reluctant to limit the CHO intake due to the lack of information related to safety issues, low CHO diets are increasing in popularity amongst both people with and without diabetes. One of these diets, the very low CHO high fat diet (VLCHF) raises concern on its impact on the lipid profile, liver, response to glucagon, and insulin dose adjustments when adopting it in the context of type 1 diabetes (T1D). The investigators recently conducted a series of interviews with people with diabetes following a VLCHF diet (Brazeau et al. Manuscript in preparation) to inquire on their reasons for adopting VLCHF as well as challenges they faced. The main reasons to initiate the diet were to limit blood glucose fluctuations and reduce medication. An issue that was frequently mentioned during the interviews was the lack of support from HCPs which often leads to not discussing it with said HCP. This is an important source of concern that can lead to additional safety issues. Our goal is to provide information regarding the safety of a VLCHF diet for T1D and the individualized insulin adjustments required. The investigators aim to evaluate the changes in daily blood glucose fluctuations after 6 weeks of a VLCHF diet, to monitor the changes in the insulin dosing and to measure impact on lipid profiles, response to glucagon, and liver function.

Official Title
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Carbohydrates Under Target for Type 1 Diabetes Management

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: Control Diet
* Other: VLCHF Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Duration of Type 1 Diabetes > 12 months On intensive insulin therapy for > 6 months Own a smartphone or tablet to use two mobile applications : Keenoa and Piezo: Achieve the Guidelines! Exclusion Criteria: Known gastroparesis (clinical diagnosis) Advanced kidney disease (eGFR < 50 mL/min) Known significant liver disease (e.g., cirrhosis, active hepatitis, liver transplantation) Recent (< 6 months) major cardiovascular even (e.g. myocardial infarction, cerebrovascular accident, major revascularization, etc.) Pregnancy (ongoing or planned in the next 6 months) Breastfeeding Severe hypoglycemia episodes or ketoacidosis in the 4 weeks prior to recruitment Claustrophobia or presence of metal devices/implants in the body

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control diet followed by VLCHF diet<br>Phase 1 (1 to 3 weeks): Insulin dose optimization with usual diet Phase 2 (6 weeks): Control diet (50% of energy from carbohydrates) Phase 3 (4 weeks): Washout period Phase 4 (6 weeks): VLCHF diet (10% of energy from carbohydrates) | Other: Control Diet<br>* Participants will be provided with a two-week menu to be consumed 3 times for each intervention, for a total of 6 weeks per intervention. For the Control diet, the diet will provide 50% of energy from CHO, 15% from protein, and 35% from lipids. Menu will be adapted to the participant's food preferences and usual caloric intake by a dietitian. Participants will be asked to limit their alcohol intake in both interventions. During this phase, participants will also have to wear a pedometer and use the Pezio: Achieve the Guidelines! mobile application to help the research assistant track their daily steps remotely.<br>Other: VLCHF Diet<br>* Participants will be provided with a two-week menu to be consumed 3 times for each intervention, for a total of 6 weeks per intervention. For the Experimental diet, the diet will provide 10% of energy from CHO, 15% from protein, and 75% from lipids. During the Experimental diet, participants will be provided with a multivitamin to reduce risk of deficiencies due to restrictions on fruits and grain products. Menu will be adapted to the participant's food preferences and usual caloric intake by a dietitian. Participants will be asked to limit their alcohol intake in both interventions. During this phase, participants will also have to wear a pedometer and use the Pezio: Achieve the Guidelines! mobile application to help the research assistant track their daily steps remotely.<br>|
| Experimental: VLCHF diet followed by Control diet<br>Phase 1 (1 to 3 weeks): Insulin dose optimization with usual diet Phase 2 (6 weeks): VLCHF diet (10% of energy from carbohydrates) Phase 3 (4 weeks): Washout period Phase 4 (6 weeks): Control diet (50% of energy from carbohydrates) | Other: Control Diet<br>* Participants will be provided with a two-week menu to be consumed 3 times for each intervention, for a total of 6 weeks per intervention. For the Control diet, the diet will provide 50% of energy from CHO, 15% from protein, and 35% from lipids. Menu will be adapted to the participant's food preferences and usual caloric intake by a dietitian. Participants will be asked to limit their alcohol intake in both interventions. During this phase, participants will also have to wear a pedometer and use the Pezio: Achieve the Guidelines! mobile application to help the research assistant track their daily steps remotely.<br>Other: VLCHF Diet<br>* Participants will be provided with a two-week menu to be consumed 3 times for each intervention, for a total of 6 weeks per intervention. For the Experimental diet, the diet will provide 10% of energy from CHO, 15% from protein, and 75% from lipids. During the Experimental diet, participants will be provided with a multivitamin to reduce risk of deficiencies due to restrictions on fruits and grain products. Menu will be adapted to the participant's food preferences and usual caloric intake by a dietitian. Participants will be asked to limit their alcohol intake in both interventions. During this phase, participants will also have to wear a pedometer and use the Pezio: Achieve the Guidelines! mobile application to help the research assistant track their daily steps remotely.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily blood glucose standard deviation | Using continuous glucose monitoring | Over the 6 weeks of each intervention diet | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time-in-target (range of 4-10 mmol/L) | Using continuous glucose monitoring | Over the 6 weeks of each intervention diet | 
| Coefficient of glucose variation | Using continuous glucose monitoring | Over the 6 weeks of each intervention diet | 
| Mean sensor glucose values (mmol/L) | Using continuous glucose monitoring | Over the 6 weeks of each intervention diet | 
| Glucose area under the curve for 2 hours post-prandial | Using continuous glucose monitoring | First and last week of each intervention diet | 
| Number of hypoglycemia episodes necessitating treatment recorded | Recorded by participants on hypoglycemia journal | Over the 6 weeks of each intervention diet | 
| Percentage of time spent in hypoglycemia ranges (< 4 mmol/L and < 3 mmol/L) | Using continuous glucose monitoring | Over the 6 weeks of each intervention diet | 
| Percentage of time spent in hyperglycemia ranges (>10 mmol/L and > 15 mmol/L) | Using continuous glucose monitoring | Over the 6 weeks of each intervention diet | 
| Daily insulin adjustments required to maintain safe blood glucose | Adjustments (basal and prandial) to avoid hypoglycemia (blood glucose < 4 mmol/L) and hyperglycemia (blood glucose > 15 mmol/L) | Over the 6 weeks of each intervention diet | 
| Short-term effects on anthropometric parameters : weight (kg) and height (cm) | Weight and height will be combined to report BMI (kg/m^2) | Following the 6 weeks of each intervention diet | 
| Short-term effects on anthropometric parameters : waist circumference (cm) | Calculated using the average of 3 measures | Following the 6 weeks of each intervention diet | 
| Short-term effects on blood lipid profiles | Total cholesterol, HDL-chol, and LDL-chol, triglycerides, Apo-B and Apo-A | Following the 6 weeks of each intervention diet | 
| Short-term effects on body composition (lean and fat mass) | Measured by DEXA (Dual-Energy X-ray Absorptiometry) | Following the 6 weeks of each intervention diet | 
| Short-term effects on inflammatory parameters | Plasma lipopolysaccharide (LPS), interleukine 6 (IL-6), monocyte chemoattractant protein-1 MCP-1) | Following the 6 weeks of each intervention diet | 
| Short-term effects on oxidative stress/redox parameters | Total and reduced glutathione | Following the 6 weeks of each intervention diet | 
| Short-term effects on blood pressure | Systolic and diastolic blood pressure | Following the 6 weeks of each intervention diet | 
| Short-term effects on liver function | Aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin, albumin | Following the 6 weeks of each intervention diet | 
| Short-term effects on resting metabolic rate | After a 10-hour fast measured by indirect calorimetry | Following the 6 weeks of each intervention diet | 
| Short-term effects on liver proton density fat fraction by MRS (MRS-PDFF) (%) | Using hepatic fat imagery (MRI) | Following the 6 weeks of each intervention diet | 
| Short-term effects on mean liver PDFF | Using hepatic fat imagery (MRI) | Following the 6 weeks of each intervention diet | 
| Short-term effects on total liver volume (mL) | Using hepatic fat imagery (MRI) | Following the 6 weeks of each intervention diet | 
| Short-term effects on total liver fat index (%.ml) | Using hepatic fat imagery (MRI) | Following the 6 weeks of each intervention diet | 
| Efficacy of glucagon in correcting hypoglycemia | Time needed to reach a blood glucose > 4 mmol/L after glucagon treatment of an insulin-induced hypoglycemia reaching 4 mmol/L at 15, 20 and 30 min post glucagon administration, peak plasma glucose level two hours after administration, insulin, glucagon, ketone and free fatty acids levels. | Following the 6 weeks of each intervention diet | 
| Modulation of postprandial glycemic response (Standardized meal-tests) | Hunger, appetite and fullness scores, lat the following times (-20, 0, 15, 30, 60, 90, 120 and 180 min, with 0 min being the start of meal consumption) | Following the 6 weeks of each intervention diet | 
| Secretion of key gastrointestinal peptides (Standardized meal-tests) | Gastrointestinal peptides : levels of glucose, insulin glucagon, GLP-1, PYY and acylated ghrelin at the following times (-20, 0, 15, 30, 60, 90, 120 and 180 min, with 0 min being the start of meal consumption), as well as their corresponding kinetics including areas under the curve (AUC), peak values and nadirs. | Following the 6 weeks of each intervention diet | 
| Questionnaire of well-being (score) | Corresponding scores of questionnaire used to assess different quality of life aspects: well-being, fatigue, nausea, hunger, appetite, desire to eat. | Following the 6 weeks of each intervention diet | 
| Questionnaire of diet satisfaction (score) | Corresponding scores of questionnaire used to assess different quality of life aspects: diet satisfaction, difficulty to follow the diet, difficulty for meal preparation. | Following the 6 weeks of each intervention diet | 
| Effects on physical activity (steps/day) | Steps per day recorded with a pedometer (PedioRxD) and mobile application (baseline and during each intervention diet) | Over the 6 weeks of each intervention diet |