Very Low Carbohydrate Diet for Type 1 Diabetes

Overseen By Belinda S Lennerz, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Must be taking: Insulin, Metformin

Must not be taking: Psychotropics, Recreational drugs

Disqualifiers: Ketoacidosis, Severe hypoglycemia, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

12 Participants Needed

Trial Summary

What is the purpose of this trial?

Despite major technological advances, management of type one diabetes mellitus (T1D) remains suboptimal, putting millions of people at risk for immediate and long-term complications. After meals, a mismatch between carbohydrate absorption rate and insulin action typically leads to alternating periods of hyper- and hypoglycemia. A conceptually promising approach to control both problems is dietary carbohydrate restriction to reduce postprandial blood glucose changes and insulin needs. In a prior survey study, the investigators documented exceptional glycemic control (HbA1c 5.67%) and low acute complication rates among 316 children and adults with T1D consuming a very-low-carbohydrate (VLC) diet. Despite these promising preliminary results, the use of VLC diets for T1D remain controversial, because of their restrictive nature and theoretical concerns regarding growth, ketoacidosis and hypoglycemia risks and efficiency of glucagon treatment for hypoglycemia. Glucagon is used as a rescue medication during severe hypoglycemia and increases blood glucose levels by mobilizing liver glycogen stores. If these stores are depleted during carbohydrate restriction, glucagon response may be inadequate and put individuals at risk for refractory hypoglycemia. A physiologic study has shown a blunted but still adequate response to glucagon in n=10 participants after following a VLCD for 1 week. Longer-term studies have not been done. To test the hypotheses that glucagon response remains adequate while following a VLC diet in the longer term, the investigators will conduct a glucagon challenge in participants who are assigned to the VLC arm of a randomized-controlled feeding study in 32 young adults with T1D who will receive a VLC vs a standard diet for 12 weeks. After an overnight fast, twelve participants in the VLC arm will receive IV insulin to lower blood glucose levels to 60 mg/dL, followed by a glucagon injection and monitoring of blood glucose levels and other metabolic fuels.

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 mentions that participants can only use insulin and metformin. If you are on other medications, you might need to stop them to participate.

What data supports the effectiveness of the very low carbohydrate diet treatment for type 1 diabetes?

Research shows that a very low carbohydrate diet can lead to significant improvements in blood sugar control and reduce insulin needs in people with type 1 diabetes. Some studies reported that this diet helped lower HbA1c levels (a measure of long-term blood sugar control) and improved quality of life. ^{1 2 3 4 5}

Is a very low carbohydrate diet safe for people with type 1 diabetes?

There are concerns about the safety of low-carbohydrate and ketogenic diets for people with type 1 diabetes, especially in children, as they may lead to poor growth and bone health. Additionally, there is a risk of diabetic ketoacidosis (a serious condition caused by high levels of ketones in the blood) due to decreased insulin effect. ^{2 6 7 8 9}

How is the very low carbohydrate diet treatment different for type 1 diabetes?

The very low carbohydrate diet (also known as the ketogenic diet) is unique for type 1 diabetes as it focuses on drastically reducing carbohydrate intake to improve blood sugar control, which is different from standard treatments that typically involve insulin management. This diet is also used in epilepsy, and while it can improve glycemic control, it requires careful monitoring to avoid complications like diabetic ketoacidosis (a dangerous condition caused by high levels of ketones in the blood). ^{2 5 9 10 11}

Research Team

Belinda Lennerz, MD PhD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for adults aged 18-40 with Type 1 Diabetes who have been managing their condition for at least a year, attend regular diabetes care visits, and use a continuous glucose monitor and insulin pump. They should have a BMI of 18.5-35 kg/m2 and stable glycemic control. Those pregnant, on restrictive diets, with significant illnesses or psychiatric conditions, substance abuse issues, recent severe diabetic complications or certain dietary restrictions cannot participate.

Inclusion Criteria

You use a continuous glucose monitor (CGM).

I have attended a diabetes care appointment in the last year.

Your body mass index (BMI) is between 18.5 and 35.

Exclusion Criteria

Pregnancy or breastfeeding

I can have an MRI and don't use strong psychiatric drugs.

You do intense exercise for more than two hours, at least three days a week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a very low carbohydrate diet or a standard diet for 12 weeks

12 weeks

Weekly monitoring visits

Glucagon Challenge

Participants in the VLC arm undergo a glucagon challenge to assess glucagon response after dietary intervention

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Very low carbohydrate diet

Trial Overview The study tests the effectiveness of a Very Low Carbohydrate Diet (VLC) in maintaining adequate glucagon response during hypoglycemia in people with Type 1 Diabetes over a longer term (12 weeks). Participants will be randomly assigned to either follow the VLC diet or standard diet and then undergo controlled testing involving induced low blood sugar followed by glucagon injection.

Participant Groups

Group I: Very low carbohydrate diet Experimental Treatment 1 Intervention

Dietary Intervention, food delivery

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Findings from Research

Participants with type 1 diabetes following a low carbohydrate diet (75 g per day) showed significant improvements in glycaemic control, with HbA1c levels decreasing from 63 to 55 mmol/mol (8.9% to 8.2%) and daily insulin use dropping from 64.4 to 44.2 units/day over 12 weeks.

The study suggests that a low carbohydrate diet can be a practical approach for managing type 1 diabetes, potentially reducing insulin requirements and aiding in weight loss, without negatively impacting other health markers like blood pressure or lipid profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised trial of the feasibility of a low carbohydrate diet vs standard carbohydrate counting in adults with type 1 diabetes taking body weight into account. Krebs, JD., Parry Strong, A., Cresswell, P., et al.[2022]

The very low-carbohydrate ketogenic (VLCK) diet significantly improved glycemic control and resulted in greater weight loss compared to recommended diets for up to 6 months in people with type 2 diabetes, based on a meta-analysis of 8 randomized controlled trials involving 648 participants.

While the VLCK diet showed benefits in lowering triglycerides and increasing HDL cholesterol, its effectiveness in controlling diabetes and weight did not persist beyond 6 months, and adherence to the diet was a major challenge for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis. Rafiullah, M., Musambil, M., David, SK.[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]

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]

A new clinical protocol was developed to safely monitor children with type 1 diabetes (T1D) on low-carbohydrate or ketogenic diets, focusing on key health parameters like growth, glycemic control, and bone health.

The protocol aims to ensure medical safety while accommodating families' dietary preferences, and its implementation will help establish informed guidelines for managing T1D in children on carbohydrate-restricted diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical management of children with type 1 diabetes on low-carbohydrate or ketogenic diets. Rydin, AA., Spiegel, G., Frohnert, BI., et al.[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]

Low-carbohydrate diets have shown positive results in treating diabetes, pre-diabetes, metabolic syndrome, and obesity, with evidence from randomized trials and meta-analyses indicating they are safe and effective for improving health outcomes in diabetic patients.

These diets can lead to significant benefits such as weight loss, reduced medication needs, and even remission in some cases of type 2 diabetes, although they are not yet widely recognized in Czech diabetology due to ongoing safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diet in diabetes mellitus treatment. Krejčí, H., Vyjídák, J., Kohutiar, M.[2019]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

A randomised trial of the feasibility of a low carbohydrate diet vs standard carbohydrate counting in adults with type 1 diabetes taking body weight into account. [2022]

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

Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis. [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. Denmark pubmed.ncbi.nlm.nih.gov

Medical management of children with type 1 diabetes on low-carbohydrate or ketogenic diets. [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. Czech Republic pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diet in diabetes mellitus treatment. [2019]

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

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

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

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

11. 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]