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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether a standard diet plan or a very low-carb diet (also known as a ketogenic or VLC diet) better helps people with prediabetes manage their blood sugar and weight. Participants are divided into two groups: one follows a typical diet plan, and the other follows a low-carb version. Both groups attend weekly online classes and have regular check-ins. This trial suits those who are overweight, have been diagnosed with prediabetes, can engage in light physical activities like walking, and are willing to follow a set diet and attend group sessions. As an unphased trial, this study offers a unique opportunity to explore effective dietary strategies for managing prediabetes.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that a very low-carbohydrate diet can be safe for people with prediabetes or type 2 diabetes. In some studies, participants following this diet experienced lower blood sugar and cholesterol levels. One study found that 57% of participants achieved diabetes remission, meaning their blood sugar normalized without medication.

These diets appear to aid in weight loss and reduce the need for insulin, a hormone that controls blood sugar. While these results are promising, more research is needed to determine if this diet is superior to others.

The standard National Diabetes Prevention Program (NDPP) is well-known and typically involves reducing calorie intake to manage weight and blood sugar. Both options in this trial have been used before, and evidence shows they are generally well-tolerated. Always consult a healthcare professional to determine what might be best. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for prediabetes because they explore different dietary approaches to prevent diabetes progression. The Standard National Diabetes Prevention Program (NDPP) is a calorie-restricted plan, but what sets the Very Low-Carbohydrate Diet (VLCD) apart is its unique adaptation of the NDPP, focusing on significantly reducing carbohydrate intake. This modified approach could offer an alternative way to manage blood sugar levels more effectively by emphasizing low-carb eating, which may be beneficial for those who struggle with traditional calorie restriction. By comparing these two strategies, researchers hope to find out which method is more effective in preventing the onset of diabetes in individuals with prediabetes.

What evidence suggests that this trial's treatments could be effective for prediabetes?

Research has shown that very low-carbohydrate diets, one of the treatment options in this trial, can help people with prediabetes control their blood sugar and lose weight. Studies have found that these diets lower HbA1c levels (which measure average blood sugar over time) and fasting blood sugar, both crucial for managing prediabetes. Additionally, very low-carb diets can reduce triglycerides (a type of fat in the blood) and improve cholesterol levels.

Conversely, the standard National Diabetes Prevention Program (NDPP), another treatment option in this trial, has a proven record of helping people lose weight and improve blood sugar through lifestyle changes, such as diet and exercise. Both methods aim to prevent prediabetes from progressing to type 2 diabetes, but the very low-carbohydrate diet might offer extra benefits for controlling blood sugar and losing weight. ^{2 3 6 7 8}

Who Is on the Research Team?

Laura Saslow, PhD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

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

Inability to provide informed consent

I have trouble chewing or swallowing.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9826205/

Very low carbohydrate (ketogenic) diets in type 2 diabetes A VLC/KD may cause reductions in HbA1c and triglycerides in those with pre‐diabetes or T2D but evidence of an advantage over other strategies is limited.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0168822725004784

Effectiveness of low-carbohydrate diets on type 2 diabetes LCDs improved glycemia short-term: HbA1c − 0.29 %, with the largest effect at 3 months. Fasting blood glucose decreased overall (−7.12 mg/dL). Weight loss was ...

3. diabetesjournals.org diabetesjournals.org/spectrum/article/33/2/133/32999/Low-Carbohydrate-and-Very-Low-Carbohydrate-Diets

Low-Carbohydrate and Very-Low-Carbohydrate Diets in ... In a monitored study of an Atkins-type diet (60), serum triglyceride levels decreased by 35%, and LDL cholesterol decreased by 10% at the end of ...

4. med.stanford.edu med.stanford.edu/news/all-news/2022/070/keto-mediterranean-diet-diabetes.html

Keto and Mediterranean diets both help manage diabetes, but ... In a trial of the two low-carb diets, both were similarly effective in controlling blood glucose. Keto's more severe carb restrictions did not ...

5. journalofmetabolichealth.org journalofmetabolichealth.org/index.php/jmh/article/view/87/287

Use of a very low carbohydrate diet for prediabetes and ... Conclusion: Very low carbohydrate ketogenic diet is effective in enhancing glucose control, weight loss and cardiovascular risk factors in T2D. Most patients ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36064937/

Very low carbohydrate (ketogenic) diets in type 2 diabetes A VLC/KD may cause reductions in HbA1c and triglycerides in those with pre-diabetes or T2D but evidence of an advantage over other strategies is limited.

7. bmj.com bmj.com/content/372/bmj.m4743

Efficacy and safety of low and very low carbohydrate diets ... At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31 ...

8. journalofmetabolichealth.org journalofmetabolichealth.org/index.php/jmh/article/view/87

Use of a very low carbohydrate diet for prediabetes and ... The VLCKD showed significant improvements in glucose control, weight loss, and reduced insulin needs in both T2D and prediabetes patients.