Diet Impact on Insulin Resistance

Overseen By Elaina Marinik, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Must not be taking: Diabetes medications, Antibiotics

Disqualifiers: Diabetes, Heart disease, Stroke, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Advancing age is associated with gut dysbiosis, low-grade chronic inflammation, progressive insulin resistance, and increased risk of type 2 diabetes (T2D). Prediabetes is present in 45-50% of middle-aged/older adults, and declines in glucose tolerance are evident in the third or fourth decade of life. Thus, there is an urgent need to identify new approaches for the prevention of type 2 diabetes among middle-aged adults. Observational research has linked intake of ultra-processed foods (UPF), which comprise \~60% of total energy intake in US adults, with increased risk of T2D. Ex vivo and animal research suggests that components of UPF alter gut microbiota composition and initiate a cascade of events leading to intestinal inflammation and impaired glycemic control. Whether mid-life adults (aged 45-65 yrs) are susceptible to the adverse impact of UPF consumption on glucose homeostasis is unknown. The overall objective of this study is to establish proof-of-concept for an impairment in glucose homeostasis following increases in UPF consumption in mid-life adults, in order to conduct a larger, more comprehensive and mechanistic trial in the future. In addition, changes in gut microbial composition and function, intestinal inflammation and permeability, serum endotoxin concentrations, and inflammatory cytokines as potential mechanisms by which UPF consumption influences glucose homeostasis will be investigated.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on stable doses of estrogen, testosterone, or antihypertensive medications for more than 6 months, you can continue taking them.

What data supports the effectiveness of the treatment for improving insulin resistance?

Research suggests that diets high in unsaturated fatty acids (like those found in some whole and minimally processed foods) are linked to better insulin resistance. Additionally, diets low in saturated fats and high in fiber, which are characteristics of whole and minimally processed foods, are associated with improved insulin sensitivity. ^{1 2 3 4 5}

Is the diet impact on insulin resistance treatment generally safe for humans?

Research indicates that high consumption of ultra-processed foods (UPF) is linked to various health risks, including obesity, type 2 diabetes, cardiovascular diseases, and increased mortality. Conversely, diets low in UPF, such as whole food or minimally processed food diets, are generally considered safer and healthier for humans. ^{6 7 8 9 10}

How does the High UPF controlled diet treatment differ from other treatments for insulin resistance?

The High UPF controlled diet is unique because it focuses on the impact of ultra-processed foods, which are often high in saturated fats and low in fiber, on insulin resistance. Unlike other dietary approaches that emphasize specific nutrient modifications, this treatment examines the broader effects of processed food consumption on insulin sensitivity. ^{1 2 11 12 13}

Research Team

Brenda M Davy, PhD, RD

Principal Investigator

Virginia Polytechnic Institute and State University

Eligibility Criteria

This trial is for middle-aged adults (45-65 years old) who are sedentary to moderately active, not planning to change their weight or activity level, and can commit to an 8-week study with daily food pickups. They must be stable in terms of medication for hormones and blood pressure if applicable, and not have a history of significant health issues like heart disease or diabetes.

Inclusion Criteria

Your weight has not changed in the past 6 months.

Verbal and written informed consent

You do not engage in regular physical activity.

Exclusion Criteria

You follow a vegetarian or vegan diet.

Pregnant or plans to become pregnant

I have a history of heart, lung, blood, hormone, or cancer-related diseases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants consume a diet containing either 81% or 0% total energy from ultra-processed foods for 6 weeks

6 weeks

Baseline and post-diet laboratory visits

Follow-up

Participants are monitored for changes in insulin sensitivity, glucose control, and other health markers after the diet intervention

4 weeks

Treatment Details

Interventions

• High UPF controlled diet
• No UPF controlled diet

Trial Overview The study tests the effects of ultra-processed foods on gut bacteria and blood sugar control. Participants will follow either a high UPF diet or a no UPF diet for eight weeks. Researchers aim to see how these diets affect glucose levels, gut microbiota changes, inflammation, and risk factors for type 2 diabetes.

Participant Groups

Group I: HIgh UPF (Ultra-processed foods) Experimental Treatment 1 Intervention

Participants will consume a diet containing 81% total energy from UPF for 6 weeks

Group II: No UPF Active Control 1 Intervention

Participants will consume a diet containing 0% total energy from UPF for 6 weeks

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Findings from Research

In a study of 7,630 participants from the NHANES database, a higher intake of unsaturated fatty acids (UFA) relative to total fats was linked to lower insulin resistance, as indicated by significant reductions in the triglyceride-glucose index and HOMA-IR scores.

Logistic regression analysis revealed that individuals with higher UFA/total fat ratios had a lower risk of developing insulin resistance, particularly among certain subgroups such as the elderly and females, suggesting that dietary adjustments could be beneficial for these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dietary intake of unsaturated fatty acids is associated with improved insulin resistance - a cross-sectional study based on the NHANES database. Chen, X., Gu, J., Huang, Y.[2023]

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]

In a study involving 1822 adults with overweight and prediabetes over 3 years, increases in both reported and estimated protein intake were linked to decreases in glycated hemoglobin (HbA1c), indicating potential benefits for blood sugar control.

While higher protein intake and lower energy intake were associated with reduced body mass index (BMI), they did not independently lead to improvements in insulin resistance (measured by HOMA-IR), suggesting that weight loss may be a key factor in managing insulin sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of changes in reported and estimated protein and energy intake with changes in insulin resistance, glycated hemoglobin, and BMI during the PREVIEW lifestyle intervention study. Drummen, M., Adam, TC., Macdonald, IA., et al.[2023]

A high carbohydrate diet, when compared to a diet high in total and saturated fats, significantly improves insulin sensitivity and lipid levels.

Subjects following an ad-lib low fat, high carbohydrate diet not only lose weight but also experience greater improvements in metabolic issues related to insulin resistance syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The central role of dietary fat, not carbohydrate, in the insulin resistance syndrome. Purnell, JQ., Brunzell, JD.[2019]

Dietary fat subtypes play a crucial role in insulin action, with saturated fats linked to obesity and insulin resistance, while polyunsaturated fats (PUFAs) are associated with improved insulin sensitivity and reduced fat accumulation, as shown in animal models.

Emerging research indicates that not only fats but also protein sources can influence insulin resistance, with certain proteins like cod showing protective effects against insulin resistance compared to others like casein or soy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet composition and insulin action in animal models. Storlien, LH., Higgins, JA., Thomas, TC., et al.[2019]

Recent research, including 30 studies, indicates that high consumption of ultra-processed foods (UPF) is linked to negative effects on metabolic health, such as increased risk of metabolic syndrome, obesity, and cardiovascular diseases.

The evidence suggests a strong need to reduce UPF consumption globally, especially among adults, although further studies are required to establish clear causal relationships and understand the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of ultra-processed food consumption on metabolic health. Costa de Miranda, R., Rauber, F., Levy, RB.[2021]

A review of 43 studies found that 37 studies linked ultra-processed food (UPF) consumption to various adverse health outcomes, including obesity, type-2 diabetes, and cardiovascular diseases in adults, and cardio-metabolic risks in children.

No studies reported any beneficial health outcomes associated with UPF consumption, highlighting the need for dietary guidelines that consider the health risks of these foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-Processed Foods and Health Outcomes: A Narrative Review. Elizabeth, L., Machado, P., Zinöcker, M., et al.[2021]

High consumption of ultra-processed foods (UPF) is linked to a significant increase in the risk of overweight/obesity (39%), high waist circumference (39%), and metabolic syndrome (79%) based on a systematic review of 23 studies.

In a large cohort of 183,491 participants followed for 3.5 to 19 years, high UPF consumption was associated with a 25% increased risk of all-cause mortality and a 29% increased risk of cardiovascular disease, indicating serious long-term health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consumption of ultra-processed foods and health status: a systematic review and meta-analysis. Pagliai, G., Dinu, M., Madarena, MP., et al.[2023]

High consumption of ultra-processed foods (UPFs), making up more than 10% of the diet, is associated with an increased risk of developing type 2 diabetes in adults, highlighting the need for better dietary habits.

UPFs are linked to various health concerns due to their high levels of sugars, sodium, and trans fats, as well as additives that may pose health risks, indicating a need for improved dietary guidelines and further research on their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between Ultra-Processed Food Consumption and Risk of Diabetes Mellitus: A Mini-Review. Almarshad, MI., Algonaiman, R., Alharbi, HF., et al.[2022]

In a study of 2,354 Iranian adults, those consuming the highest amounts of ultra-processed foods (UPFs) were found to be more than twice as likely to develop premature coronary artery disease (PCAD) compared to those with the lowest consumption levels.

The risk of severe PCAD also increased significantly with higher UPF consumption, indicating a strong association between UPF intake and both the likelihood and severity of coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between ultra processed food consumption and premature coronary artery disease: Iran premature coronary artery disease study (IPAD). Ansari, S., Mohammadifard, N., Haghighatdoost, F., et al.[2023]

In a study of 13,528 nondiabetic adults, higher carbohydrate intake, glycemic index, and adherence to certain diet patterns (like sweets/fat and southern diets) were linked to increased fasting insulin levels, indicating higher insulin resistance.

Conversely, following plant-based and alcohol/salad diet patterns was associated with lower fasting insulin levels, suggesting that these diets may help reduce the risk of chronic diseases related to insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet pattern may affect fasting insulin in a large sample of black and white adults. Gower, BA., Pearson, K., Bush, N., et al.[2022]

In a study of 21 healthy individuals, acute overfeeding with a high-carbohydrate diet improved insulin signaling in skeletal muscle, suggesting a potential increase in insulin sensitivity at the cellular level.

Conversely, overfeeding with a high-fat diet led to changes in insulin signaling that are associated with reduced insulin sensitivity, indicating that the macronutrient composition of the diet plays a crucial role in metabolic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early responses of insulin signaling to high-carbohydrate and high-fat overfeeding. Adochio, RL., Leitner, JW., Gray, K., et al.[2021]

Insulin resistance (IR) is a key predictor of type 2 diabetes, primarily driven by excess body fat from high energy intake, but dietary content can also significantly influence IR independent of weight changes.

Modifying macronutrient composition in the diet, such as through the Mediterranean diet or adjusting fat and carbohydrate types, can modestly improve insulin sensitivity by 10-30%, which may have important implications for public health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What dietary modification best improves insulin sensitivity and why? Weickert, MO.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

High dietary intake of unsaturated fatty acids is associated with improved insulin resistance - a cross-sectional study based on the NHANES database. [2023]

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

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

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

Associations of changes in reported and estimated protein and energy intake with changes in insulin resistance, glycated hemoglobin, and BMI during the PREVIEW lifestyle intervention study. [2023]

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

The central role of dietary fat, not carbohydrate, in the insulin resistance syndrome. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Diet composition and insulin action in animal models. [2019]

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

Impact of ultra-processed food consumption on metabolic health. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Ultra-Processed Foods and Health Outcomes: A Narrative Review. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Consumption of ultra-processed foods and health status: a systematic review and meta-analysis. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Relationship between Ultra-Processed Food Consumption and Risk of Diabetes Mellitus: A Mini-Review. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The relationship between ultra processed food consumption and premature coronary artery disease: Iran premature coronary artery disease study (IPAD). [2023]

11. England pubmed.ncbi.nlm.nih.gov

Diet pattern may affect fasting insulin in a large sample of black and white adults. [2022]

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

Early responses of insulin signaling to high-carbohydrate and high-fat overfeeding. [2021]

13. England pubmed.ncbi.nlm.nih.gov

What dietary modification best improves insulin sensitivity and why? [2017]