Effect of Different Carbohydrate Intake Patterns on Glycemic Control in Patients With Type 1 Diabetes

NCT06273631 | Recruiting DMC

• 1 other identifier: 2022-SR-481.A3
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, randomized, controlled, open-label clinical trial aims to evaluate the effects of different carbohydrate intake patterns on glycemic control in adults with type 1 diabetes. Participants will first complete a 2-week run-in period and will then be randomly assigned in a 1:1 ratio to one of two dietary groups. Both diets provide similar proportions of total energy from carbohydrates, protein, and fat, but differ in the sources of staple carbohydrates. In the moderate carbohydrate diet group, most staple foods are refined grains, whereas in the diverse carbohydrate diet group, approximately half of the staple foods are whole grains and legumes. 80 participants will follow the assigned dietary intervention for 2 weeks, followed by a 12-week follow-up period. The primary outcome is time in range (TIR), defined as the percentage of time that glucose levels are within the target range, measured using continuous glucose monitoring. Other measures of glycemic control, glycemic variability, insulin requirements, body measurements, metabolic indicators, and safety will also be evaluated. Exploratory analyses will assess potential changes in gut microbiota, immune function, and metabolomic profiles.

Conditions

Type 1 Diabetes; Diet Intervention; Glucose Control

Keywords

dietary fiber; autoimmunity; metabolomics; intestinal microbiota; time in range

Outcome Measures

Primary Outcomes (1)

• Time in range (TIR)

  TIR is defined as the percentage of time that glucose levels are between 3.9 and 10.0 mmol/L, as measured by continuous glucose monitoring (CGM). TIR at the end of the 2-week dietary intervention will be compared between the two groups.

  4 weeks (2 weeks after randomization)

Secondary Outcomes (27)

• Time above range(TAR)

  4 weeks (2 weeks after randomization)

• Time below range(TBR)

  4 weeks (2 weeks after randomization)

• Mean glucose (MG)

  4 weeks (2 weeks after randomization)

• Standard deviation of glucose (SD)

  4 weeks (2 weeks after randomization)

• Glucose coefficient of variation (CV)

  4 weeks (2 weeks after randomization)

Other Outcomes (3)

• Gut microbiota profile

  4 weeks (2 weeks after randomization) and 16 weeks (14 weeks after randomization)

• Metabolomic profile

  4 weeks (2 weeks after randomization) and 16 weeks (14 weeks after randomization)

• T-cell subset proportions

  4 weeks (2 weeks after randomization) and 16 weeks (14 weeks after randomization)

Study Arms (2)

diverse carbohydrate diet

EXPERIMENTAL

Carbohydrate, protein, and fat provide 45-55%, 15-20%, and 25-35% of total dietary energy, respectively. Of the staple carbohydrate sources, 45-50% are derived from refined grains and 45-50% from whole grains and legumes. Total daily energy intake is divided among three meals, with breakfast providing 25-30% of total energy, lunch 30-40%, and dinner 30-35%.

Other: diverse carbohydrate diet

moderate carbohydrate diet

OTHER

Carbohydrate, protein, and fat provide 45-55%, 15-20%, and 25-35% of total dietary energy, respectively. Of the staple carbohydrate sources, 90-95% are derived from refined grains. Total daily energy intake is divided among three meals, with breakfast providing 25-30% of total energy, lunch 30-40%, and dinner 30-35%.

Other: moderate carbohydrate diet

Interventions

diverse carbohydrate diet OTHER

Carbohydrate, protein, and fat provide 45-55%, 15-20%, and 25-35% of total dietary energy, respectively. Of the staple carbohydrate sources, 45-50% are derived from refined grains and 45-50% from whole grains and legumes. Total daily energy intake is divided among three meals, with breakfast providing 25-30% of total energy, lunch 30-40%, and dinner 30-35%.

diverse carbohydrate diet

moderate carbohydrate diet OTHER

Carbohydrate, protein, and fat provide 45-55%, 15-20%, and 25-35% of total dietary energy, respectively. Of the staple carbohydrate sources, 90-95% are derived from refined grains. Total daily energy intake is divided among three meals, with breakfast providing 25-30% of total energy, lunch 30-40%, and dinner 30-35%.

moderate carbohydrate diet

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who agree to participate in the study and provide written informed consent;
• Diagnosed with type 1 diabetes mellitus according to the ADA 2024 criteria;
• Aged 18 to 70 years, inclusive;
• Receiving exogenous insulin therapy with a stable treatment regimen for at least 2 months before enrollment (the type of insulin should remain unchanged, while the dose may be adjusted according to blood glucose levels);
• Body mass index (BMI) between 18.0 and 25.0 kg/m², inclusive;
• Glycated hemoglobin A1c (HbA1c) \<11%.

You may not qualify if:

• Type 1 diabetes mellitus in the honeymoon phase;
• Pregnant or breastfeeding women, or women for whom pregnancy cannot be ruled out;
• Patients who are vegetarians or are undergoing weight loss;
• Patients who are users of oral hypoglycemic drugs (alpha-glucosidase inhibitors, DPP-4 inhibitors, etc.);
• Use of glucocorticoids within 30 days before enrollment;
• History of severe food allergy;
• Patients with acute complications such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) within the previous 6 months;
• Patients with gastroparesis, inflammatory bowel disease or other complications;
• Patients with macroalbuminuria (albumin-to-creatinine ratio \> 34 mg/mmol) or renal insufficiency (creatinine \> 200 μmol/L);
• Patients with uncontrolled hyperthyroidism or hypothyroidism (Uncontrolled hyperthyroidism is defined as abnormal TSH and FT4. Uncontrolled hypothyroidism is defined as TSH \> 10 mIU/L.);
• History of heart disease, coronary artery disease or arrhythmia;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of normal;
• History of malignant tumors; history of tumors or surgery affecting digestion or nutrient absorption. Eligibility of participants with a history of benign tumors will be determined by the investigator;
• Patients with other uncontrolled immune system diseases or uncontrolled infections;
• Alcohol abuse, drug abuse, mental disorders, or other conditions unsuitable for study participation;

Sponsors & Collaborators

• Yang Tao: lead

Study Sites (1)

First Affiliated Hospital, Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

Related Publications (23)

• Bell E, Binkowski S, Sanderson E, Keating B, Smith G, Harray AJ, Davis EA. Substantial Intra-Individual Variability in Post-Prandial Time to Peak in Controlled and Free-Living Conditions in Children with Type 1 Diabetes. Nutrients. 2021 Nov 19;13(11):4154. doi: 10.3390/nu13114154.

  PMID: 34836409 BACKGROUND

• Clark AL, Yan Z, Chen SX, Shi V, Kulkarni DH, Diwan A, Remedi MS. High-fat diet prevents the development of autoimmune diabetes in NOD mice. Diabetes Obes Metab. 2021 Nov;23(11):2455-2465. doi: 10.1111/dom.14486. Epub 2021 Aug 2.

  PMID: 34212475 BACKGROUND

• Lejk A, Chrzanowski J, Cieslak A, Fendler W, Mysliwiec M. Effect of Nutritional Habits on the Glycemic Response to Different Carbohydrate Diet in Children with Type 1 Diabetes Mellitus. Nutrients. 2021 Oct 27;13(11):3815. doi: 10.3390/nu13113815.

  PMID: 34836071 BACKGROUND

• Thewjitcharoen Y, Wanothayaroj E, Jaita H, Nakasatien S, Butadej S, Khurana I, Maxwell S, El-Osta A, Chatchomchuan W, Krittiyawong S, Himathongkam T. Prolonged Honeymoon Period in a Thai Patient with Adult-Onset Type 1 Diabetes Mellitus. Case Rep Endocrinol. 2021 Sep 1;2021:3511281. doi: 10.1155/2021/3511281. eCollection 2021.

  PMID: 34513096 BACKGROUND

• Seidelmann SB, Claggett B, Cheng S, Henglin M, Shah A, Steffen LM, Folsom AR, Rimm EB, Willett WC, Solomon SD. Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Health. 2018 Sep;3(9):e419-e428. doi: 10.1016/S2468-2667(18)30135-X. Epub 2018 Aug 17.

  PMID: 30122560 BACKGROUND

• Jaacks LM, Crandell J, Mendez MA, Lamichhane AP, Liu W, Ji L, Du S, Rosamond W, Popkin BM, Mayer-Davis EJ. Dietary patterns associated with HbA1c and LDL cholesterol among individuals with type 1 diabetes in China. J Diabetes Complications. 2015 Apr;29(3):343-9. doi: 10.1016/j.jdiacomp.2014.12.014. Epub 2014 Dec 31.

  PMID: 25630525 BACKGROUND

• Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-99. doi: 10.1210/jcem.87.2.8182.

  PMID: 11836274 BACKGROUND

• Zhai X, Zhang L, Chen L, Lian X, Liu C, Shi B, Shi L, Tong N, Wang S, Weng J, Zhao J, Teng X, Yu X, Lai Y, Wang W, Li C, Mao J, Li Y, Fan C, Li L, Shan Z, Teng W. An Age-Specific Serum Thyrotropin Reference Range for the Diagnosis of Thyroid Diseases in Older Adults: A Cross-Sectional Survey in China. Thyroid. 2018 Dec;28(12):1571-1579. doi: 10.1089/thy.2017.0715. Epub 2018 Nov 27.

  PMID: 30351201 BACKGROUND

• Barouti AA, Bjorklund A, Catrina SB, Brismar K, Rajamand Ekberg N. Effect of Isocaloric Meals on Postprandial Glycemic and Metabolic Markers in Type 1 Diabetes-A Randomized Crossover Trial. Nutrients. 2023 Jul 10;15(14):3092. doi: 10.3390/nu15143092.

  PMID: 37513510 BACKGROUND

• Wong K, Raffray M, Roy-Fleming A, Blunden S, Brazeau AS. Ketogenic Diet as a Normal Way of Eating in Adults With Type 1 and Type 2 Diabetes: A Qualitative Study. Can J Diabetes. 2021 Mar;45(2):137-143.e1. doi: 10.1016/j.jcjd.2020.06.016. Epub 2020 Jun 27.

  PMID: 33039330 BACKGROUND

• Buehler LA, Noe D, Knapp S, Isaacs D, Pantalone KM. Ketogenic diets in the management of type 1 diabetes: Safe or safety concern? Cleve Clin J Med. 2021 Oct 1;88(10):547-555. doi: 10.3949/ccjm.88a.20121.

  PMID: 34598919 BACKGROUND

• Smart CE, Evans M, O'Connell SM, McElduff P, Lopez PE, Jones TW, Davis EA, King BR. Both dietary protein and fat increase postprandial glucose excursions in children with type 1 diabetes, and the effect is additive. Diabetes Care. 2013 Dec;36(12):3897-902. doi: 10.2337/dc13-1195. Epub 2013 Oct 29.

  PMID: 24170749 BACKGROUND

• Leow ZZX, Guelfi KJ, Davis EA, Jones TW, Fournier PA. The glycaemic benefits of a very-low-carbohydrate ketogenic diet in adults with Type 1 diabetes mellitus may be opposed by increased hypoglycaemia risk and dyslipidaemia. Diabet Med. 2018 May 8. doi: 10.1111/dme.13663. Online ahead of print.

  PMID: 29737587 BACKGROUND

• Vetrani C, Calabrese I, Cavagnuolo L, Pacella D, Napolano E, Di Rienzo S, Riccardi G, Rivellese AA, Annuzzi G, Bozzetto L. Dietary determinants of postprandial blood glucose control in adults with type 1 diabetes on a hybrid closed-loop system. Diabetologia. 2022 Jan;65(1):79-87. doi: 10.1007/s00125-021-05587-0. Epub 2021 Oct 23.

  PMID: 34689215 BACKGROUND

• Berry SE, Valdes AM, Drew DA, Asnicar F, Mazidi M, Wolf J, Capdevila J, Hadjigeorgiou G, Davies R, Al Khatib H, Bonnett C, Ganesh S, Bakker E, Hart D, Mangino M, Merino J, Linenberg I, Wyatt P, Ordovas JM, Gardner CD, Delahanty LM, Chan AT, Segata N, Franks PW, Spector TD. Human postprandial responses to food and potential for precision nutrition. Nat Med. 2020 Jun;26(6):964-973. doi: 10.1038/s41591-020-0934-0. Epub 2020 Jun 11.

  PMID: 32528151 BACKGROUND

• Kanikarla-Marie P, Jain SK. Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes. Free Radic Biol Med. 2016 Jun;95:268-77. doi: 10.1016/j.freeradbiomed.2016.03.020. Epub 2016 Mar 29.

  PMID: 27036365 BACKGROUND

• Bolla AM, Caretto A, Laurenzi A, Scavini M, Piemonti L. Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes. Nutrients. 2019 Apr 26;11(5):962. doi: 10.3390/nu11050962.

  PMID: 31035514 BACKGROUND

• Dabek A, Wojtala M, Pirola L, Balcerczyk A. Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States. Nutrients. 2020 Mar 17;12(3):788. doi: 10.3390/nu12030788.

  PMID: 32192146 BACKGROUND

• Zinn C, Lenferna De La Motte KA, Rush A, Johnson R. Assessing the Nutrient Status of Low Carbohydrate, High-Fat (LCHF) Meal Plans in Children: A Hypothetical Case Study Design. Nutrients. 2022 Apr 12;14(8):1598. doi: 10.3390/nu14081598.

  PMID: 35458160 BACKGROUND

• Pasmans K, Meex RCR, van Loon LJC, Blaak EE. Nutritional strategies to attenuate postprandial glycemic response. Obes Rev. 2022 Sep;23(9):e13486. doi: 10.1111/obr.13486. Epub 2022 Jun 10.

  PMID: 35686720 BACKGROUND

• Saslow LR, Mason AE, Kim S, Goldman V, Ploutz-Snyder R, Bayandorian H, Daubenmier J, Hecht FM, Moskowitz JT. An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial. J Med Internet Res. 2017 Feb 13;19(2):e36. doi: 10.2196/jmir.5806.

  PMID: 28193599 BACKGROUND

• Rydin AA, Spiegel G, Frohnert BI, Kaess A, Oswald L, Owen D, Simmons KM. Medical management of children with type 1 diabetes on low-carbohydrate or ketogenic diets. Pediatr Diabetes. 2021 May;22(3):448-454. doi: 10.1111/pedi.13179. Epub 2021 Feb 16.

  PMID: 33470021 BACKGROUND

• Turton JL, Raab R, Rooney KB. Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. PLoS One. 2018 Mar 29;13(3):e0194987. doi: 10.1371/journal.pone.0194987. eCollection 2018.

  PMID: 29596460 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Immune System Diseases

Study Officials

• Tao Yang, MD/PhD

  First Affiliated Hospital, Nanjing Medical University, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tao Yang, MD/PhD

CONTACT

86-25-83718836; yangt@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Participants and study personnel responsible for implementing the dietary intervention are not masked because the staple foods differ in appearance, type, and taste between the two groups. Investigators responsible for outcome assessment are masked to treatment allocation. Physicians responsible for insulin dose adjustment are also masked to treatment allocation and dietary assignment. Investigators responsible for data management and statistical analysis remain masked until the analysis is completed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor, Chief physician

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: February 22, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 10, 2026

Record last verified: 2026-09

Locations

CN (1)