Effect of Whole Fruit on Glycemic Control in Adults With Type 2 Diabetes

Study Overview
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Brief Summary
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Diabetes costs the U.S. healthcare system more than any other disease, and nearly half of Americans will develop either diabetes or prediabetes in their lifetime. It is therefore critical to find new strategies to treat or reverse diabetes. One such approach is adopting a healthy diet, which can dramatically improve blood sugar levels in adults with type 2 diabetes and even induce diabetes remission. Despite this, not much is known about which food groups are most effective at improving blood sugar levels in patients with diabetes. Interestingly, of the various food groups that comprise the Mediterranean diet, epidemiologic data suggests that whole fruit may be one of the most efficacious at both preventing type 2 diabetes and improving blood sugar in patients with type 2 diabetes. However, few clinical trials have investigated the effects of whole fruit on blood sugar control. This study will therefore be the first to determine the effects of increasing whole fruit as a food group in type 2 diabetes patients. This supervised controlled feeding trial will test whether consuming a diet rich in whole fruit for 12 weeks can induce diabetes remission and can improve blood sugar, liver fat, and cardiovascular health in adults with type 2 diabetes. Thereafter, participants will be followed for up to one year. As a secondary aim, this study will also test whether consuming a large amount of fructose in whole food form negatively affects liver fat and cardiovascular health.

Detailed Description
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Pre-registration notes: The primary endpoint is glycemic control, which will be analyzed hierarchically in descending order of importance as: Diabetes remission rate (endpoint #1) Medication effect score (endpoint #2) Fasting glucose and HbA1c (endpoints #3-4) Oral glucose tolerance test and continuous glucose monitoring measures (endpoints #5-14) while the secondary endpoints (endpoints #15-20) will all be evaluated with equal importance.

Official Title
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Effect of Whole Fruit on Glycemic Control in Adults With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Behavioral: High-Fruit Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20-65 years old BMI between 27.0-45.0 kg/m^2 First diagnosed with type 2 diabetes within the past 6 years HbA1c between 6.0-9.5%% Exclusion Criteria: On insulin Diagnosis of diabetes before age 18 Estimated glomerular filtration rate < 45 ml/min per 1.732 m^2 Heart attack in the past 6 months or severe or unstable heart failure On weight loss medication Change in the dosage of a chronic medication that may affect study endpoints within the past 3 months Clinically significant laboratory abnormality (e.g. abnormal hemoglobin levels) Significant gastrointestinal disease, major gastrointestinal surgery, or gallstones Significant cardiovascular, renal, cardiac, liver, lung, adrenal, or nervous system disease that might compromise safety or data validity Evidence of cancer (other than non-melanoma skin cancer) within the last 5 years Lost or gained more than 5 kg of weight in the past 6 months Pregnant, planning to become pregnant in the next 12 months, or breastfeeding Major psychiatric condition that would affect the ability to participate in the study Not able to eat the provided study meals Behavioral factors or circumstances that may impede adhering to the dietary intervention Not able to do the MRI/MRS abdominal scan, such as due to claustrophobia, implanted metal objects, or a body girth of 60 cm or greater

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-Fruit Diet<br> | Behavioral: High-Fruit Diet<br>* Participants will consume a diet rich in whole fruit. During Phase I (Weeks 1-4; supervised controlled feeding), participants will gradually increase the amount of whole fruit they consume, eventually reaching 50% of calories from whole fruit. In Phase II (Week 5-12; supervised controlled feeding), participants will consume a whole fruit-rich, eucaloric diet that provides 50% of calories in the form of whole fruit. The non-fruit portion of the diet will be styled as a Mediterranean Diet. Participants will be required to approximately keep their weight stable during Phases I and II. In the Follow-Up Phase (Months 4-12; free-living), participants will be instructed to continue consuming at least one-third of their diet as whole fruit and to make healthy food choices.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diabetes remission rate | Remission rate will be measured in two ways. At the end of Phase II, it will be quantified as the percentage of patients who achieve non-diabetic levels of fasting glucose without the aid of any anti-hyperglycemic pharmacologic therapy or ongoing procedures.. During the Follow-up period, it will be quantified as the percentage of patients who achieve non-diabetic levels of both fasting glucose and HbA1c without the aid of any anti-hyperglycemic pharmacologic therapy or ongoing procedures. | Change from baseline (Week 0) to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Diabetes medication usage | As quantified by the Medication Effect Score | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Fasting glucose | mg/dl | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| HbA1c | percentage | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| 2-hour glucose tolerance | mg/dl | Change from baseline to Weeks 4 and 12 | 
| Mean glucose during a 3-hour Oral Glucose Tolerance Test (OGTT) | mg/dl | Change from baseline to Weeks 4 and 12 | 
| Mean insulin during a 3-hour OGTT | mU/l | Change from baseline to Weeks 4 and 12 | 
| Mean C-peptide during a 3-hour OGTT | ng/ml | Change from baseline to Weeks 4 and 12 | 
| Fasting insulin | mU/l | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Fasting C-peptide | ng/ml | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Insulin sensitivity | Insulin sensitivity (dl/kg/min/μU/ml) during a 3-hour OGTT, as measured by the Oral Minimal Model | Change from baseline to Weeks 4 and 12 | 
| Insulin secretion | Beta-cell responsivity index during a 3-hour OGTT, as measured by the Oral Minimal Model | Change from baseline to Weeks 4 and 12 | 
| Beta-cell function | Insulinogenic index as measured during the first 15 minutes of a 3-hour OGTT | Change from baseline to Weeks 4 and 12 | 
| Mean 24-hour glucose levels, peak glucose levels, and mean amplitude of glycemic excursions (MAGE), as measured using continuous glucose monitoring | mg/dl | Change from baseline to Weeks 4 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intrahepatic lipid (liver fat) | Percentage as measured using Magnetic Resonance Spectroscopy (MRS) and 3-point M-Dixon Magnetic Resonance Imaging (MRI) | Change from baseline to Weeks 4 and 12 | 
| Fasting lipids | Total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl) | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Systolic and diastolic blood pressure | mm Hg | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Heart rate | beats per minute | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Number of cardiovascular medications used | Number for each category of medication (e.g., anti-hypertensive medications) | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 
| Dosage of cardiovascular medications used | Dosages for each category of medication (e.g., anti-hypertensive medications) | Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, whole fruit, diabetes remission, glycemic control, liver fat, intrahepatic lipid, controlled feeding trial