Low Carbohydrate Diet vs. High Carbohydrate Diet in Type 1 Diabetes (HiLo12)

Low Carbohydrate Diet vs. High Carbohydrate Diet in Type 1 Diabetes: A Randomized Crossover Study

The aim of the study is to investigate glycemic control during a low carbohydrate diet compared with during a high carbohydrate diet in adults with insulin pump treated type 1 diabetes.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Low carbohydrate diet; Other: High carbohydrate diet

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital

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:

• Type 1 diabetes ≥3 years
• Insulin pump use ≥1 year
• HbA1c ≥53 mmol/mol (7.0%)
• BMI 20-27 kg/m2
• Willingness to count carbohydrates and use the insulin pump bolus calculator for all boluses during the intervention periods
• Willingness to use continuous glucose monitoring consistently during the intervention periods

Exclusion Criteria:

• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
• Use of SGLT-2-inhibitors
• Use of corticosteroids during or within 30 days prior to the intervention periods
• Celiac disease
• Inflammatory bowel disease
• Macroalbuminuria
• Active proliferative retinopathy combined with an HbA1c ≥ 75 mmol/mol (9.0%)
• Known or suspected alcohol or drug abuse
• Other concomitant medical or psychological condition that according to the investigator's assessment makes the patient unsuitable for study participation

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: Low Carbohydrate Diet; < 100 grams of carbohydrate per day	Other: Low carbohydrate diet
Experimental: High Carbohydrate Diet; > 250 grams of carbohydrate per day	Other: High carbohydrate diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Time Spent in Euglycemia	Time spent with glucose values 4.0-10.0 mmol/l assessed by continuous glucose monitoring	12 weeks - from baseline to end of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Glucose	Mean glucose value assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Standard Deviation of Glucose	Standard deviation of glucose values assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Coefficient of Variation of Glucose	Coefficient of variation of glucose values assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Mean Amplitude of Glycemic Excursions	Mean amplitude of glycemic excursions (MAGE) assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Time Spent in Hypoglycemia	Percentage of time spent with glucose values ≤ 3.9 mmol/l assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Time Spent in Hyperglycemia	Time spent with glucose values > 10.0 mmol/l assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Change in A1c	Change in hemoglobin A1c	From baseline to 12 weeks
AUC Low	Difference in area under the curve <4.0 mmol/l assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
AUC High	Difference in area under the curve >10.0 mmol/l assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Post Breakfast Glucose Excursion	Difference in post breakfast glucose excursion assessed by continuous glucose monitoring	12 weeks - from baseline to end of study
Severe Hypoglycemia	Number of severe hypoglycemia episodes (glucagon or intravenous glucose administration)	From baseline to 12 weeks
Total Daily Dose	Total daily insulin dose	12 weeks - from baseline to end of study
Total Daily Basal Insulin 24 Hour	Total daily basal insulin dose in the time range 00:00-24:00	12 weeks - from baseline to end of study
Total Nightime Basal Insulin	Total nighttime basal insulin in the time range 00:00-06:00	From baseline to 12 weeks
Total Daytime Basal Insulin	Total daytime basal insulin in the time range 06:00-24:00	12 weeks - from baseline to end of study
Total Daily Bolus Insulin	Difference in total daily bolus insulin	12 weeks - from baseline to end of study
Blood Glucose Readings	Number of blood glucose readings	12 weeks - from baseline to end of study
Carbohydrate Servings	Number of daily carbohydrate servings (one serving ≥ 15 grams)	12 weeks - from baseline to end of study
Body Composition	Change in fat mass (% of total body weight) assessed by Dual-energy X-ray Absorptiometry	12 weeks - from baseline to end of study
Weight	Change in weight	12 weeks - from baseline to end of study
Hip Circumference	Change in hip circumference	12 weeks - from baseline to end of study
Waist Circumference	Change in waist circumference	From baseline to 12 weeks
Systolic Blood Pressure	Change in systolic blood pressure	12 weeks - from baseline to end of study
Diastolic Blood Pressure	Change in diastolic blood pressure	12 weeks - from baseline to end of study
Heart Rate	Change in heart rate	12 weeks - from baseline to end of study
Diabetes Treatment Satisfaction	Change in Diabetes Treatment Satisfaction Questionnaire score. Score range: 0-36, with higher values representing higher degrees of treatment satisfaction.	12 weeks - from baseline to end of study
Hypoglycemia Fear	Change in Hypoglycemia Fear Survey score. Score range: 0-52, with higher scores indicating higher degrees of fear of hypoglycemia.	12 weeks - from baseline to end of study
Cholesterol	Change in total cholesterol	12 weeks - from baseline to end of study
HDL	Change in HDL	12 weeks - from baseline to end of study
LDL	Change in LDL	12 weeks - from baseline to end of study
Triglycerides	Change in triglycerides	12 weeks - from baseline to end of study
Free Fatty Acids	Change in free fatty acids	12 weeks - from baseline to end of study
Sodium	Change in sodium	12 weeks - from baseline to end of study
Potassium	Change in potassium	12 weeks - from baseline to end of study
Creatinine	Change in creatinine	12 weeks - from baseline to end of study
Urate	Change in urate	12 weeks - from baseline to end of study
Albumin	Change in albumin	12 weeks - from baseline to end of study
Hemoglobin	Change in hemoglobin	12 weeks - from baseline to end of study
Leucocytes	Change in leucocytes	12 weeks - from baseline to end of study
Thrombocytes	Change in thrombocytes	12 weeks - from baseline to end of study
Iron	Change in iron	12 weeks - from baseline to end of study
Transferrin	Change in transferrin	12 weeks - from baseline to end of study
Ferritin	Change in ferritin	12 weeks - from baseline to end of study
Folate	Change in folate	12 weeks - from baseline to end of study
Vitamin B-12	Change in vitamin B-12	12 weeks - from baseline to end of study
Magnesium	Change in magnesium	12 weeks - from baseline to end of study
Zinc	Change in zinc	12 weeks - from baseline to end of study
U-alb-crea Ratio	Change in urine albumin-creatinine ratio	12 weeks - from baseline to end of study
Supar	Change in Supar	12 weeks - from baseline to end of study
CRP	Change in CRP	12 weeks - from baseline to end of study
IL-1	Change in IL-1	12 weeks - from baseline to end of study
IL-6	Change in IL-6	12 weeks - from baseline to end of study
IL-8	Change in IL-8	12 weeks - from baseline to end of study
TNF-alpha	Change in TNF-alpha	12 weeks - from baseline to end of study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carbohydrate Intake	Daily carbohydrate intake assessed by insulin pump download	12 weeks - from baseline to end of study
Ketones	Morning blood ketone values obtained 7 times during the study period. A single value was calculated for each study participant based on an average of the 7 datapoints.	Spot test at week 0, 2, 4, 6, 8, 10 and 12

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital

Publications and helpful links

General Publications

• Schmidt S, Christensen MB, Serifovski N, Damm-Frydenberg C, Jensen JB, Floyel T, Storling J, Ranjan A, Norgaard K. Low versus high carbohydrate diet in type 1 diabetes: A 12-week randomized open-label crossover study. Diabetes Obes Metab. 2019 Jul;21(7):1680-1688. doi: 10.1111/dom.13725. Epub 2019 Apr 21.
• Ji L, Li L, Ma J, Li X, Li D, Meng B, Lu W, Sun J, Liu Y, Takayanagi G, Wang Y. Efficacy and safety of teneligliptin added to metformin in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin: A phase 3, randomized, double-blind, placebo-controlled study. Endocrinol Diabetes Metab. 2021 Jan 20;4(2):e00222. doi: 10.1002/edm2.222. eCollection 2021 Apr.
• Al-Sari N, Schmidt S, Suvitaival T, Kim M, Trost K, Ranjan AG, Christensen MB, Overgaard AJ, Pociot F, Norgaard K, Legido-Quigley C. Changes in the lipidome in type 1 diabetes following low carbohydrate diet: Post-hoc analysis of a randomized crossover trial. Endocrinol Diabetes Metab. 2021 Jan 4;4(2):e00213. doi: 10.1002/edm2.213. eCollection 2021 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: August 30, 2016
• First Submitted That Met QC Criteria: August 30, 2016
• First Posted (Estimate): September 5, 2016

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

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: HiLo12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No