Carbohydrates Under Target for Type 1 Diabetes Management

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.

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Control Diet; Other: VLCHF Diet

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H2W1R7
      • Institut de recherches cliniques de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control diet followed by VLCHF diet; 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; 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.; Other: VLCHF Diet; 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.
Experimental: VLCHF diet followed by Control diet; 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; 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.; Other: VLCHF Diet; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: McGill University

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2019
• Primary Completion (Actual): March 23, 2020
• Study Completion (Actual): March 23, 2020

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CUT-T1D

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No