Ketogenic Diet for Type 1 Diabetes

Overseen By Belinda Lennerz, MD PhD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Must be taking: Insulin

Disqualifiers: Vegan, Eating disorders, Major illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 14

Duration: 9 months

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to test the effects of a ketogenic diet on the progression and control of type 1 diabetes in children with newly diagnosed diabetes. The main questions to answer are: * Does a ketogenic diet prolong the honeymoon period of type 1 diabetes? * Does a ketogenic diet improve diabetes control? * Is a ketogenic diet safe, acceptable and sustainable in children with newly diagnosed diabetes? * What are the microbiome, inflammatory and metabolic changes linking diet to β-cell function? Participants will receive a combination of free meals, groceries, micronutrient supplements, and intensive diet and diabetes education for 9 months. * Diabetes care devices will be connected for cloud-based data collection. * Bi-weekly data downloads and remote check-ins will assess dietary intake, satisfaction with diet and study procedures, and possible safety concerns. * During four study visits held at at baseline, 1, 5, and 9 months, an intravenous catheter (IV) will be placed for collection of 5 blood samples before and up to 2 hours after a liquid test meal (protein shake) to assess insulin response. A stool sample will also be collected to assess microbiome changes. * Children and their caregivers may be invited to participate in a semi-structured interview, and online questionnaires to assess their experience with the diet and diabetes care, general well-being and quality of life. * Children and their caregivers may be invited to participate in a follow-up visit to evaluate long-term effects after 24 months. Comparison will be made between a ketogenic vs standard diet.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those using medications other than insulin that could affect metabolism or blood sugar levels.

Is the ketogenic diet safe for humans?

The ketogenic diet has been used for over 50 years and generally does not have major safety concerns for the general public. However, for people with type 1 diabetes, there may be an increased risk of hypoglycemia (low blood sugar) and dyslipidemia (abnormal blood fat levels), so caution is advised. ^{1 2 3 4 5}

How is the ketogenic diet treatment different for type 1 diabetes?

The ketogenic diet is unique for type 1 diabetes as it focuses on high fat and low carbohydrates, which can improve blood sugar control but requires careful monitoring to avoid diabetic ketoacidosis (a dangerous condition caused by high levels of ketones). Unlike standard treatments that primarily involve insulin management, this diet alters the body's energy source, which can also help manage epilepsy in some patients. ^{1 6 7 8 9}

What data supports the effectiveness of the ketogenic diet treatment for type 1 diabetes?

Research shows that a ketogenic diet, which is low in carbohydrates and high in fats, can improve blood sugar control in people with type 1 diabetes. One study found that a patient on this diet had significant improvements in diabetes-related health markers and reduced insulin needs by 70%. ^{3 10 11 12 13}

Who Is on the Research Team?

Belinda Lennerz, MD PhD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children aged 5-12 with newly diagnosed type 1 diabetes, confirmed by insulin requirement and autoimmunity markers. The family must be committed to participating in the study's education and dietary intervention.

Inclusion Criteria

My family and I can join in the study's education and follow its diet plan.

My child is between 5 and 12 years old.

Within one month of diabetes diagnosis

Exclusion Criteria

Eating disorders as assessed by Chede-Q8

Dietary needs or habits incompatible with the study meal plans (e.g., vegan, major food intolerances/allergies, ketogenic)

Major psychiatric illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a ketogenic or standard diet along with diabetes education and monitoring for 9 months

9 months

Bi-weekly remote check-ins, 5 in-person visits at baseline, 1, 5, 9, and 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 months

In-person visits at 9 and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet
• Standard Diet

Trial Overview The trial tests if a ketogenic diet can extend the 'honeymoon' period of type 1 diabetes, improve control over it, and assess its safety and sustainability. It involves free meals, supplements, education, regular check-ins, blood sample collection after a test meal, stool samples for microbiome analysis.

How Is the Trial Designed?

Group I: ketogenic diet Experimental Treatment 1 Intervention

The diet will be high in protein and healthy fats and comprise meat, fish, fibrous vegetables, nuts, dairy, and berries. Macronutrient composition will be \~ 5% carbohydrate, 20% protein, 70% fat. Participants will receive a daily multi-vitamin, magnesium supplement, and supplemental salt (bouillon cubes) to ascertain micronutrient sufficiency and help with transition to the diet.

Group II: standard diet Active Control 1 Intervention

The diet will be consistent with prevailing dietary guidelines and recommendations and contain meat, fish, grains, vegetables, fruit and dairy. At least 50% of grain-based products will be whole grains. Meats will be primarily lean, and dairy products will be fat-free or low-fat. Macronutrient composition will be \~50% carbohydrate (\<10% added sugars), 20% protein, 30% fat. Participants will receive a daily multi-vitamin supplement to ascertain micronutrient sufficiency.

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

Indiana University

Collaborator

Trials

1,063

Recruited

1,182,000+

Published Research Related to This Trial

In a study of 11 adults with Type 1 diabetes following a ketogenic diet for an average of 2.6 years, participants achieved excellent glycaemic control with a mean HbA1c of 5.3%, indicating effective blood sugar management.

However, while the diet improved glycaemic control, it was also linked to dyslipidaemia, with high cholesterol levels in many participants, and a notable occurrence of hypoglycaemic episodes, suggesting potential health risks that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Leow, ZZX., Guelfi, KJ., Davis, EA., et al.[2022]

A systematic review of nine studies on low-carbohydrate diets for managing type 1 diabetes found that while some studies reported significant reductions in HbA1c, the overall effect was inconclusive due to significant variability among the studies.

The review highlights the need for more rigorous primary studies to better understand the impact of low-carbohydrate diets on diabetes management, as current evidence is limited and mixed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. Turton, JL., Raab, R., Rooney, KB.[2022]

A ketogenic diet significantly improved diabetes-related biomarkers in a male type 1 diabetic patient, bringing them into the non-diabetic range and reducing total daily insulin requirements by 70%.

The patient reported a substantial enhancement in quality of life, suggesting that dietary changes can have positive health outcomes for individuals with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing type 1 diabetes mellitus with a ketogenic diet. Gardemann, C., Knowles, S., Marquardt, T.[2023]

In a study of 1040 children with type 1 diabetes, 39% reported experience with low-carbohydrate diets, with 5.8% currently following one, indicating that such diets are not uncommon among this population.

Children on low-carbohydrate diets showed better glycemic control, with lower average blood sugar levels and more time spent in the target range, but there was also a tendency for increased episodes of hypoglycemia, suggesting a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Carbohydrate Diet among Children with Type 1 Diabetes: A Multi-Center Study. Neuman, V., Plachy, L., Pruhova, S., et al.[2022]

A low-carbohydrate, high-fat ketogenic diet (KD) was effective in improving glycemic control in two type 2 diabetic patients over a 12-week period, with both patients showing significant reductions in HBA1C levels (2.4% and 2.5%).

The female patient was able to reduce her diabetic medication by 75%, while the male patient eliminated all diabetic medications, highlighting the potential of KDs as a viable dietary strategy for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing glycemic control in type 2 diabetic patients through the use of a low-carbohydrate, high-fat, ketogenic diet: a review of two patients in primary care. Rallis, S.[2020]

There is a noted association between type 1 diabetes and epilepsy, with potential mechanisms including genetic factors and metabolic issues, but the exact relationship remains unclear.

Current evidence is insufficient to recommend the ketogenic diet for children with both epilepsy and type 1 diabetes, highlighting the need for more research to assess its safety and efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intractable Seizures in Children With Type 1 Diabetes: Implications of the Ketogenic Diet. Vidmar, KK., Pollock, AJ.[2023]

In a study involving 89 participants with type 2 diabetes, a very low-calorie ketogenic (VLCK) diet led to significantly greater weight loss and improved glycemic control compared to a standard low-calorie diet over 4 months.

The VLCK diet was found to be safe and well-tolerated, with no serious adverse events reported and no significant changes in laboratory safety parameters, indicating it can be a viable option for managing obesity in T2DM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Goday, A., Bellido, D., Sajoux, I., et al.[2022]

Ketogenic diets, which consist of over 70% fat and very low carbohydrates, may be more effective than low-fat diets for treating obesity and diabetes, showing potential benefits in reducing blood glucose and insulin levels.

A well-formulated ketogenic diet appears to be safe for the general public and could be considered a first-line treatment for obesity and diabetes, although more high-quality clinical trials are needed to explore its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed. Ludwig, DS.[2023]

The ketogenic diet (KD) is considered a relatively safe treatment for refractory childhood epilepsy, with severe adverse effects occurring in less than 0.5% of children, and no deaths attributed to the diet.

Common adverse effects include gastrointestinal disturbances and hyperlipidemia, but the main reason for discontinuation of the diet was lack of efficacy rather than safety concerns, highlighting the need for careful medical supervision during its implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. Cai, QY., Zhou, ZJ., Luo, R., et al.[2018]

A 15-month follow-up of a 3.5-year-old girl with type 1 diabetes on a ketogenic diet (KD) showed no reported seizures despite persistent epileptiform activity on EEG, suggesting potential benefits of the KD in managing epilepsy.

The girl's glycosylated hemoglobin (HbA1c) levels improved significantly, indicating excellent glycemic control without severe side effects, demonstrating that the KD can be safely used in patients with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type 1 diabetes and epilepsy: efficacy and safety of the ketogenic diet. Dressler, A., Reithofer, E., Trimmel-Schwahofer, P., et al.[2017]

In a study of 26 individuals with type 1 diabetes, a high-monounsaturated-fat diet led to a 7% reduction in low-density lipoprotein (LDL) cholesterol, suggesting potential benefits for heart health.

For those who strictly adhered to the diet, significant improvements were observed, including an 18% reduction in total triglycerides and a 48% reduction in very low-density lipoprotein (VLDL) cholesterol, indicating a favorable change in the lipoprotein profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of a high-monounsaturated-fat diet on lipid profile in subjects with type 1 diabetes. Strychar, I., Ishac, A., Rivard, M., et al.[2015]

A 42-year-old woman with type 2 diabetes experienced euglycemic diabetic ketoacidosis (euDKA) after starting a sodium-glucose co-transporter 2 (SGLT2) inhibitor while on a very low carbohydrate ketogenic diet (VLCKD), highlighting the risk of this combination.

After recovering from euDKA and stopping the SGLT2 inhibitor, she successfully resumed a VLCKD under medical supervision and maintained ketosis safely for 2 years, demonstrating that with proper monitoring, VLCKD can be safely reimplemented post-euDKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SUCCESSFUL REIMPLEMENTATION OF A VERY LOW CARBOHYDRATE KETOGENIC DIET AFTER SGLT2 INHIBITOR ASSOCIATED EUGLYCEMIC DIABETIC KETOACIDOSIS. Fieger, EI., Fadel, KM., Modarres, AH., et al.[2022]

The ketogenic diet can be successfully implemented in a child with both epilepsy and type 1 diabetes, despite the challenges in distinguishing between diet-induced ketosis and diabetic ketoacidosis.

This case highlights the potential for the ketogenic diet to manage myoclonic astatic epilepsy while also addressing the child's diabetes, suggesting a dual benefit in carefully monitored settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet for the treatment of myoclonic astatic epilepsy in a child with type 1 diabetes mellitus. Aylward, NM., Shah, N., Sellers, EA.[2017]

Citations

1. England pubmed.ncbi.nlm.nih.gov

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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Managing type 1 diabetes mellitus with a ketogenic diet. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Low-Carbohydrate Diet among Children with Type 1 Diabetes: A Multi-Center Study. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Optimizing glycemic control in type 2 diabetic patients through the use of a low-carbohydrate, high-fat, ketogenic diet: a review of two patients in primary care. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Intractable Seizures in Children With Type 1 Diabetes: Implications of the Ketogenic Diet. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Type 1 diabetes and epilepsy: efficacy and safety of the ketogenic diet. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Impact of a high-monounsaturated-fat diet on lipid profile in subjects with type 1 diabetes. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

SUCCESSFUL REIMPLEMENTATION OF A VERY LOW CARBOHYDRATE KETOGENIC DIET AFTER SGLT2 INHIBITOR ASSOCIATED EUGLYCEMIC DIABETIC KETOACIDOSIS. [2022]

13. Canada pubmed.ncbi.nlm.nih.gov

The ketogenic diet for the treatment of myoclonic astatic epilepsy in a child with type 1 diabetes mellitus. [2017]