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

University of Alabama at Birmingham34 enrolled

Overview

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, 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 improve glycemic control and cardiometabolic health in weight-stable adults with type 2 diabetes. The primary endpoint is glycemic control. Since changes in medication doses can skew the interpretation of glycemic outcomes, glycemic control will be assessed hierarchically (in descending order of importance) using (a) attainment of nondiabetic glycemia without medications (as a proxy for diabetes remission), (b) medication effect scores, (c) mean glucose during an oral glucose tolerance test, and (d) 24-hour mean glucose from continuous glucose monitoring. As secondary aims, this study will also test whether consuming a large amount of fructose in whole food form affects liver fat, pancreatic fat, and cardiovascular disease risk factors.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

High-Fruit DietBEHAVIORAL

In this supervised controlled feeding study, participants will consume a diet rich in whole fruit. During the Ramp-Up Phase (Weeks 1-4), participants will gradually increase the amount of whole fruit they consume, eventually reaching 50% of calories from whole fruit. In the Main Phase (Weeks 5-12), 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 throughout the intervention.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 20-70 years old * BMI ≤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

Outcomes

Primary Outcomes

Diabetes Remission Rate

Percentage of patients who can maintain non-diabetic levels 24-hour mean glucose without the aid of pharmacotherapy at week 12

Time frame: Change from baseline to week 12

Medication Effect Score (MES)

% (or percentage). This quantity estimates the percentage by which all anithyperglycemic medications taken by a patient would lower HbA1c levels (i.e., percent of glycated hemoglobin molecules). Higher values indicate a higher dose and/or potency of medications.

Time frame: Change from baseline to Week 12

Mean Glucose During a 3-hour Oral Glucose Tolerance Test (OGTT)

mg/dl

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Mean 24-hour Glucose Levels as Measured by Continuous Glucose Monitoring (CGM), Adjusted for Any Changes in Medication Doses Via the MES

mg/dl

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Secondary Outcomes

Insulin Sensitivity

Insulin sensitivity (dl/kg/min/μU/ml) during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model.

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Dynamic Beta-Cell Responsivity

Phi\_dynamic during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi\_dynamic is a measure of beta-cell responsiveness during first-phase insulin secretion. It is a dimensionless index (arbitrary units), where higher values denote greater insulin secretion.

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Static Beta-Cell Responsivity

Phi\_static during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi\_static is a measure of beta-cell responsiveness during second-phase insulin secretion. The units of measure are min\^-1, and higher values denote greater insulin secretion.

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Mean Insulin During a 3-hour OGTT

mU/l

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Mean C-peptide During a 3-hour OGTT

ng/ml

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Mean Amplitude of Glycemic Excursions From CGM

mg/dl

Time frame: Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)"

Fasting Glucose

mg/dl