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

Trial Summary

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.

What data supports the effectiveness of the treatment Dietary Interventions for Insulin Resistance?

Research shows that low-carbohydrate diets can effectively reduce high blood sugar levels and improve insulin resistance, which is when the body doesn't respond well to insulin. Additionally, the Mediterranean diet has been found to delay the need for diabetes medication, suggesting it may help manage insulin resistance. ^{1 2 3 4 5}

Is the Mediterranean or low-carbohydrate diet safe for humans?

The Mediterranean diet is generally considered safe and beneficial for health, especially for those at high cardiometabolic risk. However, long-term use of low-carbohydrate ketogenic diets may pose risks, such as kidney issues and metabolic acidosis, particularly in people with obesity. ^{6 7 8 9 10}

How does the dietary intervention for insulin resistance differ from other treatments?

This dietary intervention is unique because it includes a Mediterranean low carbohydrate diet, which has been shown to delay the need for glucose-lowering drugs in type 2 diabetes patients compared to a low-fat diet. It focuses on reducing carbohydrate intake while incorporating healthy fats, which may improve insulin sensitivity and delay disease progression. ^{4 11 12 13 14}

What is the purpose of this trial?

This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.

Research Team

Tracey McLaughlin, MD

Principal Investigator

Stanford University, Department of Medicine, Division of Endocrinology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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 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 (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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Changes in nutritional pattern, insulin sensitivity and glucose tolerance during weight loss in obese patients from a Mediterranean area. [2011]

2. England pubmed.ncbi.nlm.nih.gov

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

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

The role of low-carbohydrate diets in the intensive care unit. [2023]

4. France pubmed.ncbi.nlm.nih.gov

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

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

Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Low-carbohydrate ketogenic diets in body weight control: A recurrent plaguing issue of fad diets? [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Intensive dietary intervention promoting the Mediterranean diet in people with high cardiometabolic risk: a non-randomized study. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Body composition changes and cardiometabolic benefits of a balanced Italian Mediterranean Diet in obese patients with metabolic syndrome. [2022]

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

Pilot study of a ketogenic diet in relapsing-remitting MS. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Mediterranean diet and health outcomes: a systematic meta-review. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Dietary patterns and management of type 2 diabetes: A systematic review of randomised clinical trials. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Weight loss, diet composition and cardiovascular risk. [2019]

13. Germany pubmed.ncbi.nlm.nih.gov

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

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

Thematic review series: patient-oriented research. Nutritional determinants of insulin resistance. [2022]