Dietary Interventions for Insulin Resistance

Overseen By Tracey L McLaughlin, MD, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: Weight loss meds, Statins

Disqualifiers: Diabetes, Major organ disease, others

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

Compensation: Varies

Number of Visits: 3

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different diets affect insulin resistance, a condition where the body struggles to use insulin properly. Participants will follow one of three diets: a Mediterranean low-carb diet, a standard low-carb diet, or a low-fat diet. Researchers will assess the impact of these diets on body weight and insulin sensitivity using blood and other tests. The study seeks individuals aged 35-65 who have maintained a stable weight, are not diabetic, and have a BMI between 25 and 35. As an unphased trial, it offers a unique opportunity to contribute to understanding how dietary changes can improve health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using weight loss medication, statins, or oral steroids.

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

Previous studies have shown that the Mediterranean and low-carbohydrate diets are easy for participants to follow. Research indicates these diets aid in weight loss and improve health markers like insulin sensitivity, without major safety concerns. Similarly, low-fat diets have proven safe and have similar effects on insulin resistance as low-carbohydrate diets.

For the Mediterranean low-carbohydrate diet, studies showed better weight loss compared to other diets, with no major side effects. Evidence suggests the standard low-carbohydrate diet improves insulin sensitivity, with no significant safety issues noted. Meanwhile, low-fat diets have shown safety comparable to low-carbohydrate diets, with similar effects on weight and insulin resistance.

Overall, various studies support that these diets are generally safe and well-tolerated. Participants have not reported major side effects, making these diets a potentially safe choice for managing insulin resistance. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these dietary interventions for insulin resistance because they offer personalized approaches to managing the condition through targeted dietary changes. The Mediterranean Low Carbohydrate Diet emphasizes healthy unsaturated fats, which could improve heart health while managing insulin levels. The Standard Low Carbohydrate Diet focuses on typical American dietary fats, aiming to reduce carbohydrates and potentially improve insulin sensitivity. Meanwhile, the Low Fat, Healthy Carbohydrate Diet stands out by promoting complex carbohydrates and low fat intake, which might enhance metabolic health. Unlike standard treatments that often rely on medication, these diets offer a holistic approach to managing insulin resistance through tailored nutrition plans.

What evidence suggests that this trial's dietary interventions could be effective for insulin resistance?

Research has shown that low-carbohydrate diets can improve the body's insulin use, which is crucial for managing blood sugar. In this trial, participants will follow different dietary interventions. The Mediterranean Low Carbohydrate Diet, one of the study arms, includes healthy fats and fewer carbs and has been shown in studies to help control blood sugar and improve insulin response. Another arm, the Standard Low Carbohydrate Diet, has also demonstrated effectiveness in controlling blood sugar; one study found a 75% improvement in insulin use. Meanwhile, the Low Fat, Healthy Carbohydrate Diet, another treatment arm in this trial, can be just as effective, helping to lower blood sugar and insulin levels. Research suggests that both low-fat and low-carb diets are good options for improving insulin use. ^{1 2 5 6 7}

Who Is on the Research Team?

Tracey McLaughlin, MD

Principal Investigator

Stanford University, Department of Medicine, Division of Endocrinology

Are You a Good Fit for This Trial?

This trial is for adults aged 35-65 with a BMI of 25-35 who have maintained a stable weight and are not diabetic. It's not suitable for those with eating disorders, psychiatric conditions, high blood pressure, diabetes, history of certain weight loss surgeries, heavy alcohol use, recent significant weight change or major organ disease.

Inclusion Criteria

Your body mass index (BMI) is between 25 and 35.

I am between 35 and 65 years old.

I do not have diabetes.

Exclusion Criteria

Your blood pressure is higher than 160/100 mmHg.

I have a serious condition affecting a major organ.

My weight has changed in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Controlled Diet and Weight Intervention

Participants undergo a controlled diet and weight intervention to monitor changes in cellular processes and insulin sensitivity.

12 weeks

3 visits (in-person) at baseline, peak weight, and post weight loss

Follow-up

Participants are monitored for safety and effectiveness after the diet and weight intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dietary Intervention Mediterranean Low Carbohydrate Diet
• Dietary Intervention Standard Low Carbohydrate Diet
• Dietary Intervention Standard Low Fat Diet

Trial Overview The study tests how different diets (Mediterranean Low Carbohydrate Diet vs Standard Low Carbohydrate Diet vs Standard Low Fat Diet) affect the body's response to insulin over a period of 12 weeks. Participants will undergo diet interventions and regular monitoring including blood tests and radiological assessments.

How Is the Trial Designed?

Group I: Standard Low Carbohydrate Diet Experimental Treatment 1 Intervention

Assigned participants will receive instruction by a registered dietitian on a low carbohydrate diet that is high in fats found in the typical American diet. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Group II: Mediterranean Low Carbohydrate Diet Experimental Treatment 1 Intervention

Assigned participants will receive instruction by a registered dietitian on a diet that is high in unsaturated fats and low in carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Group III: Low Fat, Healthy Carbohydrate Diet Experimental Treatment 1 Intervention

Assigned participants will receive instruction by a registered dietitian on a low fat diet that is high in complex carbohydrates. Total caloric intake will be adjusted to induce a supervised metabolic challenge defined as weight gain of approximately 2.5 kg over 5 weeks followed by 3-5kg weight loss over 8 weeks.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A review of 20 randomized controlled trials found that while low carbohydrate diets (LCDs) did not show significant overall benefits compared to low fat diets (LFDs) for diabetes management, some LCDs did improve glycemic control in a few cases.

The Mediterranean, vegan, and vegetarian diets were more effective in controlling blood sugar levels and promoting weight loss, suggesting these dietary patterns should be considered in public health strategies for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary patterns and management of type 2 diabetes: A systematic review of randomised clinical trials. Papamichou, D., Panagiotakos, DB., Itsiopoulos, C.[2022]

Low-carbohydrate, high-fat (LCHF) nutrition therapy can significantly improve health outcomes in critically ill patients by reducing hyperglycemia, enhancing respiratory function, and potentially decreasing hospital stays and costs.

LCHF therapy may be particularly beneficial in the ICU setting as it helps conserve protein and glucose for essential metabolic functions, making it a promising area for further research, especially in the context of COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of low-carbohydrate diets in the intensive care unit. Hajjar, J., Dziegielewski, C., Dickson, S., et al.[2023]

A trial involving patients with recently diagnosed type 2 diabetes found that following a Mediterranean diet can significantly delay the need for glucose-lowering medications compared to a low-fat diet.

This dietary approach may provide a beneficial strategy for managing blood sugar levels and improving overall health in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type 2 diabetes: Mediterranean diet delays need for drug therapy. [2022]

A 3-month intensive Mediterranean diet intervention led to significantly greater weight loss (6.8 kg) and improved cardiometabolic risk factors compared to a conventional intervention, which only resulted in a minor weight loss (0.7 kg).

Participants in the intensive intervention maintained their weight loss over 9 months, while the conventional group regained weight, highlighting the long-term benefits of the intensive dietary approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive dietary intervention promoting the Mediterranean diet in people with high cardiometabolic risk: a non-randomized study. Grimaldi, M., Ciano, O., Manzo, M., et al.[2018]

A 20-week behavior program for 54 obese patients following a Mediterranean diet led to significant weight loss and improvements in cardiovascular risk factors and insulin sensitivity, despite a decrease in monounsaturated fatty acid intake.

The study found that while caloric restriction improved insulin sensitivity and reduced various health markers, the lipoprotein profile remained unchanged, suggesting that dietary modifications should carefully consider the balance of fats consumed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in nutritional pattern, insulin sensitivity and glucose tolerance during weight loss in obese patients from a Mediterranean area. Calle-Pascual, AL., Saavedra, A., Benedi, A., et al.[2011]

Low carbohydrate diets (LCD) have been shown to effectively manage insulin resistance and metabolic syndrome, leading to remission of Type 2 Diabetes Mellitus, improved lipid profiles, and significant reductions in liver fat.

Current guidelines support the use of LCDs as a safe and valid treatment option for patients with Type 2 Diabetes and obesity, highlighting the need for structured education for clinicians to enhance implementation in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of low carbohydrate diets on insulin resistance and the metabolic syndrome. Foley, PJ.[2023]

Very low carbohydrate diets (less than 60 g per day) are more effective for weight loss over 6 months compared to low-fat diets, although both have poor long-term adherence.

Most studies showed that LDL cholesterol levels did not increase and triglyceride levels significantly decreased on low-carbohydrate diets, indicating potential cardiovascular benefits, but more research is needed to compare the long-term safety and efficacy of different dietary approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss, diet composition and cardiovascular risk. Noakes, M., Clifton, P.[2019]

The modified Atkins diet (KDMAD) is safe and well-tolerated in individuals with relapsing multiple sclerosis (MS), with no subjects experiencing worsening of their condition during the 6-month study involving 20 participants.

KDMAD led to significant improvements in fatigue and depression scores, as well as reductions in body mass index and total fat mass, indicating potential benefits for managing symptoms of MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of a ketogenic diet in relapsing-remitting MS. Brenton, JN., Banwell, B., Bergqvist, AGC., et al.[2022]

The Mediterranean diet, characterized by its balanced intake of macronutrients and micronutrients, is recommended for long-term weight maintenance and health benefits, unlike short-term restrictive diets that are difficult to sustain.

Low-carbohydrate ketogenic diets may pose medical risks, particularly for individuals with obesity, as they can lead to metabolic acidosis and renal issues, potentially reducing life expectancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets? Schutz, Y., Montani, JP., Dulloo, AG.[2021]

A 6-month dietary intervention using the Italian Mediterranean Diet (IMD) in 80 patients with metabolic syndrome led to significant weight loss, with body weight decreasing from 102.59 kg to 92.39 kg and waist circumference reducing from 112.23 cm to 92.42 cm (p < 0.001).

The IMD also resulted in improved cardiometabolic health, with 52% of participants resolving their metabolic syndrome and significant reductions in blood pressure, fasting glucose, and harmful cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body composition changes and cardiometabolic benefits of a balanced Italian Mediterranean Diet in obese patients with metabolic syndrome. Di Daniele, N., Petramala, L., Di Renzo, L., et al.[2022]

The Mediterranean diet (MeDi) is associated with improved health outcomes and may help reduce the risk of non-communicable diseases (NCDs), as summarized from 33 articles including systematic reviews and meta-analyses.

Combining the MeDi with physical activity and avoiding tobacco and excessive alcohol consumption enhances its health benefits, suggesting a comprehensive approach to promoting better health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mediterranean diet and health outcomes: a systematic meta-review. Martinez-Lacoba, R., Pardo-Garcia, I., Amo-Saus, E., et al.[2019]

Low-carbohydrate diets have been shown to effectively reduce high blood glucose levels in diabetes patients without the need for weight loss, and they can even lead to a reduction or elimination of diabetes medications.

The evidence suggests that low-carbohydrate diets should be considered as a primary treatment for type 2 diabetes and as a beneficial adjunct to medication for type 1 diabetes, with fewer side effects compared to commonly prescribed diabetic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Feinman, RD., Pogozelski, WK., Astrup, A., et al.[2022]

Insulin resistance is a key factor in metabolic syndrome and type 2 diabetes, characterized by a delayed insulin response after meals in type 2 diabetics.

An effective dietary approach to combat insulin resistance includes a carbohydrate-rich, fat-reduced lactovegetable diet, with reduced meal frequency to promote longer periods without food, helping to lower insulin levels and prevent further resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of type 2 (non-insulin dependent) diabetes and the metabolic syndrome with diet]. Bruns, W.[2015]

Excess body fat is the primary factor contributing to insulin resistance, but having a higher proportion of lean body mass can help mitigate this effect, and weight loss generally improves insulin sensitivity.

Diets high in saturated fats and low in dietary fiber are linked to reduced insulin sensitivity, while replacing saturated fats with monounsaturated fats and increasing fiber intake may promote better insulin sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thematic review series: patient-oriented research. Nutritional determinants of insulin resistance. McAuley, K., Mann, J.[2022]

Citations

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Effects of Low-Carbohydrate versus Mediterranean Diets ... The average weight loss was 5%, being 58% greater in the low-carbohydrate-group than Mediterranean-group. Fasting plasma glucose and glucose ...

2. 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 ... The researchers found that both diets improved blood glucose control, as indicated by similar drops in HbA1c levels (9% on keto and 7% on ...

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Weight Loss with a Low-Carbohydrate, Mediterranean, or ... In this 2-year dietary-intervention study, we found that the Mediterranean and low-carbohydrate diets are effective alternatives to the low-fat ...

4. mdpi.com mdpi.com/2072-6643/16/1/95

Comparative Evaluation of a Low-Carbohydrate Diet and a ... In this study, the results indicate that a low-carbohydrate diet might have superior efficacy compared to a Mediterranean diet in facilitating weight loss and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0002916522001198

Effects of a low-carbohydrate diet on insulin-resistant ... A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol.

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Effects of Low-Fat, Mediterranean, or Low-Carbohydrate ... Among all participants, average SU decreases were 48 μmol/L at 6 months and 18 μmol/L at 24 months, with no differences between diets (P > 0.05) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S000291652301972X

Mediterranean and carbohydrate-restricted diets ... First, in line with previous reports, a Mediterranean-like diet was found to be beneficial, with a 17% reduction in 10-y total mortality for each SD increment ...