Diabetes Prevention Programs for Prediabetes

(LEAP Trial)

Overseen By Laura Saslow, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Anti-obesity, Glucose-lowering, Corticosteroids, Warfarin

Disqualifiers: Diabetes, Pregnancy, Bariatric surgery, others

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

Compensation: Varies

Number of Visits: 6

Duration: 12 months

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is comparing two diet programs to see which one better helps people with prediabetes control their blood sugar and lose weight. One program follows a regular diet, while the other focuses on eating very few carbohydrates. Participants will also attend group classes for support and education.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as anti-obesity medications, glucose-lowering medications other than metformin, oral corticosteroids, and loop diuretics at specified doses. If you are taking any of these, you may need to stop them to participate.

What data supports the effectiveness of the treatment for prediabetes in the Diabetes Prevention Programs?

Research suggests that very low-carbohydrate diets, like the ketogenic diet, can help with weight loss and improve blood sugar control, which are important for preventing type 2 diabetes. These diets have shown promise in managing type 2 diabetes and related conditions, indicating potential benefits for prediabetes as well. ^{1 2 3 4 5}

Is a very low-carbohydrate diet safe for people with prediabetes?

Research suggests that very low-carbohydrate diets, including ketogenic diets, are generally safe for short-term use in people with type 2 diabetes and prediabetes, but their long-term safety is still being studied. ^{3 4 6 7 8}

How does the very low-carbohydrate diet treatment for prediabetes differ from other treatments?

The very low-carbohydrate diet (also known as a ketogenic diet) is unique because it focuses on significantly reducing carbohydrate intake, which can directly lower blood sugar levels after meals and promote weight loss by reducing insulin levels and enabling fat breakdown. This approach contrasts with the standard Diabetes Prevention Program, which emphasizes a low-fat, calorie-restricted diet and regular physical activity. ^{3 4 8 9 10}

Research Team

Laura Saslow, PhD

Principal Investigator

University of Michigan

Eligibility Criteria

The Leap Study is for adults with prediabetes, indicated by an HbA1c level between 5.7% and 6.4%. Participants should be overweight, able to do light exercise like walking, have their doctor's approval, and be willing to attend group sessions and adhere to a diet plan. People using certain medications or with specific health conditions are excluded.

Inclusion Criteria

Willingness to follow a prescribed diet, be randomized, self-weight, track diet, and report physical activity minutes

I am overweight according to my BMI.

Your HbA1c level is between 5.7% and 6.4% when checked at the start of the study.

Exclusion Criteria

Pregnant or planning to become pregnant during the intervention period

I cannot read, write, or speak English.

Inability to provide informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Testing

Baseline testing with a continuous glucose monitor and randomization to diet groups

1 week

1 visit (in-person)

Treatment

Participants follow either the standard NDPP or very low-carbohydrate diet with weekly group classes over Zoom

12 months

Weekly virtual classes for 4 months, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Check-ins and follow-up visits throughout the study

Treatment Details

Interventions

• Standard NDPP
• Very low-carbohydrate diet

Trial Overview This study compares two approaches within the Diabetes Prevention Program: a standard method versus a very low-carbohydrate diet in improving blood sugar control and weight loss. Participants will be randomly assigned to one of these diets for a year with support through weekly online classes that later become monthly.

Participant Groups

Group I: Very low-carbohydrate diet (VLCD) Experimental Treatment 1 Intervention

VLCD is an adaptation of the standard NDPP curriculum, which preserves all features with the exception of altered dietary advice.

Group II: Standard NDPP Active Control 1 Intervention

12-month long, calorie-restricted NDPP

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

The very-low-calorie ketogenic diet (VLCKD) is an effective lifestyle intervention for managing overweight and obesity, leading to significant weight loss and improvements in conditions like hypertension, type 2 diabetes, and dyslipidemia.

This review synthesizes evidence from four key studies, highlighting VLCKD's potential benefits and offering practical recommendations for its implementation in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very-low-calorie ketogenic diet for the management of obesity, overweight and related disorders. Castellana, M., Biacchi, E., Procino, F., et al.[2021]

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]

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]

A 21-day very low-calorie ketogenic diet (VLCKD) resulted in significant weight loss and improvements in insulin resistance without negatively impacting overall nutritional status or causing adverse changes in liver and kidney function.

Both VLCKD1 and VLCKD2 led to similar reductions in body mass index and fat mass, but also resulted in increased levels of uric acid and creatinine, indicating the need for monitoring these parameters during such diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study. Colica, C., Merra, G., Gasbarrini, A., et al.[2022]

In a modified Diabetes Prevention Program (DPP) for patients with non-alcoholic fatty liver disease (NAFLD), 79% of participants completed the program, leading to significant weight loss and improvements in liver health indicators over 12 months.

Key improvements included reduced hepatic steatosis and liver enzymes, indicating enhanced liver function, although there was a noted increase in low-density lipoprotein levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modification of the diabetes prevention program for the treatment of nonalcoholic fatty liver disease: A pilot study. Hershman, M., Torbjornsen, K., Pang, D., et al.[2023]

The Intensive Lifestyle Intervention (ILI) in the Diabetes Prevention Program (DPP) effectively helped approximately 3800 high-risk adults with prediabetes achieve weight loss through dietary and exercise modifications, demonstrating a practical approach to delaying or preventing type 2 diabetes.

The DPP and its follow-up, the DPP Outcomes Study (DPPOS), highlight the importance of lifestyle changes in managing prediabetes, particularly in a diverse population, suggesting that these interventions can be tailored to various ethnic backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Diabetes Through the Lifestyle Intervention: Lessons Learned from the Diabetes Prevention Program and Outcomes Study and its Translation to Practice. Hoskin, MA., Bray, GA., Hattaway, K., et al.[2019]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Very-low-calorie ketogenic diet for the management of obesity, overweight and related disorders. [2021]

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

Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease-A randomized controlled trial. [2022]

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

Testing a very low-carbohydrate adaption of the Diabetes Prevention Program among adults with prediabetes: study protocol for the Lifestyle Education about prediabetes (LEAP) trial. [2023]

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

Very low carbohydrate (ketogenic) diets in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. [2023]

5. 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]

6. 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]

7. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

[VLCD and VLCKD in the treatment of obese people with non-insulin-dependent diabetes or prediabetes: clinical evidence and reflections.] [2022]

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

Modification of the diabetes prevention program for the treatment of nonalcoholic fatty liver disease: A pilot study. [2023]

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

Prevention of Diabetes Through the Lifestyle Intervention: Lessons Learned from the Diabetes Prevention Program and Outcomes Study and its Translation to Practice. [2019]