Effect of a Dietary Intervention on Insulin Requirements in Type 1 Diabetes (T1D)

• ClinicalTrials.gov Identifier: NCT04944316
• Recruitment Status: Recruiting
• First Posted: June 29, 2021
• Last Update Posted: April 19, 2022
• Sponsor: Physicians Committee for Responsible Medicine
• Information provided by (Responsible Party): Physicians Committee for Responsible Medicine

Study Description

Brief Summary:

The purpose of this study is to compare the effects of a low-fat, plant-based dietary intervention and a portion-controlled dietary intervention (compliant with current American Diabetes Association (ADA) guidelines) on the management of type 1 diabetes in adults. The primary outcome measure of this study is insulin requirements (measured as the total daily dose (TDD) of insulin or basal and bolus insulin units injected per day). The study duration is 12 weeks.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Behavioral: Dietary intervention	Not Applicable

Detailed Description:

Type 1 diabetes is a chronic autoimmune disorder characterized by loss of β-cell mass and function in the pancreas, leading to reduced secretion of insulin and hyperglycemia. The management of type 1 diabetes requires the administration of exogeneous insulin. Total daily dose (TDD) of insulin, a measure of the total amount of exogeneous insulin utilized per day, can be affected by multiple factors including insulin resistance, carbohydrate intake, body weight, and body composition. While the pathogenesis of type 1 diabetes and type 2 diabetes differ, a low-fat, plant-based diet has been shown to reduce insulin resistance, reduce body weight, improve body composition, and improve glycemic control in individuals with type 2 diabetes. A low-fat, plant-based diet has also been shown to improve β-cell function in individuals who are overweight. This finding is consistent with other research that shows that therapies that reduce body fat, or modify the distribution of body fat, improve β-cell function and glucose homeostasis. To date, a low-fat, plant-based diet has never been adequately tested in adults with type 1 diabetes. The purpose of this study is to compare the effects of low-fat, plant-based dietary intervention and a portion-controlled dietary intervention (compliant with current American Diabetes Association (ADA) guidelines) on insulin requirements in adults with type 1 diabetes.

Using a parallel group design, participants with type 1 diabetes will be randomly assigned to follow a low-fat, plant-based diet or a portion-controlled diet (compliant with current ADA guidelines) for 12 weeks. The principal dependent measures of this study are TDD of insulin, hemoglobin A1c (HbA1c), interstitial fluid glucose levels, and 24-hour carbohydrate: insulin ratio. Secondary and tertiary dependent measures include inflammatory biomarkers, blood lipids, body weight, diet quality, diet acceptability, and medication use.

The investigators hypothesize that both the low-fat, plant-based dietary intervention and the portion-controlled dietary intervention will elicit changes in insulin requirements, HbA1c, variability in interstitial glucose levels, insulin sensitivity, and body weight in participants with type 1 diabetes. The investigators further hypothesize that the low-fat, plant-based dietary intervention will confer a more substantial effect on changes in insulin requirements, HbA1c, insulin sensitivity, variability in interstitial glucose levels, and body weight in participants with type 1 diabetes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Care Provider)
• Primary Purpose: Treatment
• Official Title: Physicians Committee for Responsible Medicine - A Randomized, Controlled Study of the Effect of a Low-fat, Plant-based Diet on Insulin Requirements in Individuals With Type 1 Diabetes
• Actual Study Start Date: January 19, 2022
• Estimated Primary Completion Date: December 30, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Low-fat, vegan diet; For a 12-week period, participants will be asked to follow a low-fat, vegan diet which consists of whole grains, vegetables, legumes, and fruits, with no restriction on energy intake. Animal products and added oils will be excluded. In choosing grain products and starchy vegetables (e.g., bread, potatoes), participants will be encouraged to select those retaining their natural fiber and having a glycemic index <70, using tables standardized to a value of 100 for glucose.	Behavioral: Dietary intervention; Low-fat, plant-based diet
Active Comparator: Portion-controlled diet; For a 12-week period, participants will be asked to follow a portion-controlled diet that is compliant with American Diabetes Association (ADA) guidelines. This diet will include individualized diet plans that reduce daily energy intake by 500-1,000 kcal for overweight (body mass index > 25 kg/m2) participants and keep carbohydrate intake reasonably stable over time. It will derive 15-20% from protein, <7% saturated fat, 60-70% carbohydrate and monounsaturated fats and ≤200 mg/day of cholesterol/day.	Behavioral: Dietary intervention; Portion-controlled diet (compliant with ADA guidelines)

Outcome Measures

Primary Outcome Measures :

1. Total Insulin Dose [ Time Frame: Change from week 0 to week 12 ]
   A sum of basal and bolus insulin units (U) injected per day. An average from three (3) days (two (2) workdays and one (1) weekend day) will be utilized.
2. Glycemic Control [ Time Frame: Change from week 0 to week 12 ]
   Hemoglobin A1c (HbA1c), an index of glycemic control, will be utilized.
3. Glycemic Variability [ Time Frame: Change from week 0 to week 12 ]
   Glycemic variability will be assessed through use of a continuous glucose monitoring (CGM) system that will measure the concentration of glucose in the interstitial fluid. Participants will be instructed to wear a CGM (Dexcom g6 Platinum CGM System with an enhanced algorithm, software 505, Dexcom, Inc.) and record its readings at preset increments (after an overnight fast, before each meal, 2 hours after each meal, and before going to bed) daily. Participants will be prompted to submit CGM data to investigators on a weekly basis.
4. 24-hour Carbohydrate to Insulin Ratio [ Time Frame: Change from week 0 to week 12 ]
   Calculated as the total number of grams (g) of dietary carbohydrate to total units (U) of insulin administered.

Secondary Outcome Measures :

1. Body Weight [ Time Frame: Change from week 0 to week 12 ]
   Change in body weight measured on a calibrated scale.
2. Concentration of Plasma Lipids [ Time Frame: Change from week 0 to week 12 ]
   Change in plasma cholesterol & triglycerides.
3. High-sensitivity C-reactive Protein (hs-CRP) [ Time Frame: Change from week 0 to week 12 ]
   Implemented as a biomarker for absolute cardiovascular disease risk prediction.
4. Tumor necrosis factor - α (TNF-α) [ Time Frame: Change from week 0 to week 12 ]
   Implemented to assess levels of systemic inflammation.
5. Interleukin (IL) - 1 (IL-1) and interleukin-6 (IL-6) [ Time Frame: Change from week 0 to week 12 ]
   Implemented to assess levels of systemic inflammation.

Other Outcome Measures:

1. Medication Use [ Time Frame: Change from week 0 to week 12 ]
   Participants will be asked to report changes in their medication use.
2. Diet Quality [ Time Frame: Change from week 0 to week 12 ]
   Dietary intake will be assessed using 3-day dietary records. Participants will be instructed to record all dietary intake for 3 consecutive days, including 2 weekdays and 1 weekend day. Records will be analyzed using Nutrition Data System for Research software version 2018, developed by the Nutrition Coordinating Center (NCC), University of Minnesota, Minneapolis, MN, US.
3. Diet Acceptability [ Time Frame: Change from week 0 to week 12 ]
   The Food Acceptability Questionnaire (FAQ), a self-reported measure, will be implemented to assess the subjective responses (palatability; satisfaction; ease of preparation; financial feasibility; and perceived physical benefits) of participants to their baseline diets and the intervention diet. The FAQ has twelve (12) total questions. Eleven (11) of the questions are scored on a Likert scale (1-7) and one (1) unscored question (physical benefits) will prompt the participant to "check all that apply." A higher FAQ score corresponds with a more positive subjective response.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria:

1. Type 1 diabetes
2. Men and women ≥ 18 years of age
3. Stable insulin regimen for past 3 months

Exclusion criteria:

1. Type 2 or gestational diabetes
2. Body mass index ≥ 40 kg/m2
3. HbA1c ≥ 12.0%
4. Smoking or drug abuse during the past six months
5. Alcohol consumption of more than 2 drinks per day or the equivalent, episodic increased drinking (e.g., more than 2 drinks per day on weekends), or a history of alcohol abuse or dependency followed by any current use
6. Unstable medical or psychiatric illness
7. Already following a low-fat vegan diet
8. Pregnant or breastfeeding, or plans of pregnancy within the study period
9. Lack of English fluency
10. Unable or unwilling to participate in all components of the study
11. Evidence of an eating disorder

Contacts and Locations

Contacts

Contact: Tatiana Znayenko-Miller, MS; 202-527-7317; tznayenkomiller@pcrm.org

Locations

United States, District of Columbia

Physicians Committee for Responsible Medicine; Recruiting

Washington, District of Columbia, United States, 20016

Contact: Tatiana Znayenko-Miller, MS tznayenkomiller@pcrm.org

Sponsors and Collaborators

Physicians Committee for Responsible Medicine

Investigators

• Principal Investigator: Hana Kahleova, MD, PhD; Physicians Committee for Responsible Medicine

More Information

Publications:

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Anderson JW, Zeigler JA, Deakins DA, Floore TL, Dillon DW, Wood CL, Oeltgen PR, Whitley RJ. Metabolic effects of high-carbohydrate, high-fiber diets for insulin-dependent diabetic individuals. Am J Clin Nutr. 1991 Nov;54(5):936-43. doi: 10.1093/ajcn/54.5.936.

American Diabetes Association. Standards of Medical Care in Diabetes-2018 Abridged for Primary Care Providers. Clin Diabetes. 2018 Jan;36(1):14-37. doi: 10.2337/cd17-0119. No abstract available.

Pastors JG, Franz MJ, Warshaw H, Daly A, Arnold MS. How effective is medical nutrition therapy in diabetes care? J Am Diet Assoc. 2003 Jul;103(7):827-31. doi: 10.1016/s0002-8223(03)00466-8. No abstract available.

Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB.

Mari A, Tura A, Gastaldelli A, Ferrannini E. Assessing insulin secretion by modeling in multiple-meal tests: role of potentiation. Diabetes. 2002 Feb;51 Suppl 1:S221-6. doi: 10.2337/diabetes.51.2007.s221.

Kahleova H, Mari A, Nofrate V, Matoulek M, Kazdova L, Hill M, Pelikanova T. Improvement in beta-cell function after diet-induced weight loss is associated with decrease in pancreatic polypeptide in subjects with type 2 diabetes. J Diabetes Complications. 2012 Sep-Oct;26(5):442-9. doi: 10.1016/j.jdiacomp.2012.05.003. Epub 2012 Jun 4.

American Dietetic Association; Dietitians of Canada. Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets. J Am Diet Assoc. 2003 Jun;103(6):748-65. doi: 10.1053/jada.2003.50142.

Barnard ND, Akhtar A, Nicholson A. Factors that facilitate compliance to lower fat intake. Arch Fam Med. 1995 Feb;4(2):153-8. doi: 10.1001/archfami.4.2.153.

Becker MH. The health belief model and personal health behavior. Health Educ Monogr. 1974;2:324-508.

Barnard N, Scialli AR, Bertron P, Hurlock D, Edmonds K. Acceptability of a Therapeutic Low-Fat, Vegan Diet in Premenopausal Women. J Nutr Educ. 2000;32(6):314-319. doi:10.1016/S0022-3182(00)70590-5

• Responsible Party: Physicians Committee for Responsible Medicine
• ClinicalTrials.gov Identifier: NCT04944316
• Other Study ID Numbers: Pro00048903
• First Posted: June 29, 2021
• Last Update Posted: April 19, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases