Diabetes Mellitus, Type 2
Conditions
Keywords
insulin sensitivity, glycemic control, intramyocellular, nutrition, hepatocellular
Brief summary
The purpose of this study is to compare the effects of a low-fat, plant-based dietary intervention and a portion-controlled dietary intervention (compliant with current American Diabetes Association (ADA) guidelines) on changes in intramyocellular and hepatocellular lipid content in adults with type 2 diabetes. Changes in insulin sensitivity and glycemic control will also be assessed in this study. The study duration is 44 weeks.
Detailed description
Type 2 diabetes is a disease characterized by discordance between the amount of insulin produced by pancreatic β-cells and the amount of insulin required to overcome insulin resistance in the liver and peripheral tissues. The development of insulin resistance has been strongly associated with the prolonged accumulation of lipids (fats) in the liver cells (hepatocellular lipid) and muscle cells (intramyocellular lipid). Conventional pharmacologic therapeutics for type 2 diabetes, like metformin, are designed to reduce the accumulation of hepatocellular and intramyocellular lipids and, thereby, augment insulin sensitivity. Research has shown that a low-fat, plant-based diet, in which the consumption of lipids is limited, is a similarly effective therapeutic intervention for the reduction of hepatocellular and intramyocellular lipid content and the improvement of insulin sensitivity in type 2 diabetes. The purpose of this study is to compare the effects of low-fat, plant-based dietary intervention and a portion-controlled dietary intervention (compliant with current American Diabetes Association (ADA) guidelines) on hepatocellular and intramyocellular lipid content in adults with type 2 diabetes. Using a cross-over design, participants with type 2 diabetes will be randomly assigned to start with a plant-based or a portion-controlled diet for 22 weeks. The two groups will then switch to the opposite diet regimen for an additional 22 weeks. Before and after each intervention period, the investigators will measure intramuscular and liver fat content. The investigators will also assess the relationship between these variables, insulin sensitivity, and glycemic control. The investigators hypothesize that both dietary interventions will result in reductions in intramuscular and liver fat content, and that these changes will be associated with improvements in insulin sensitivity and glycemic control in individuals with type 2 diabetes. The investigators further hypothesize that the low-fat, plant-based dietary intervention will elicit greater changes in intracellular lipid concentration, compared with the portion-controlled dietary intervention.
Interventions
BEHAVIORALDietary intervention
Low-fat, plant-based diet and a portion-controlled diet
Sponsors
Yale University
Physicians Committee for Responsible Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
randomized, cross-over
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
are as follows: 1. Men and women with type 2 diabetes treated by diet and/or oral hypoglycemic agents other that sulfonylureas 2. Age ≥18 years 3. Body mass index 26-40 kg/m2 4. Medications (antidiabetic, antihypertensive, and lipid-lowering) have been stable for the past 3 months 5. HbA1c between 6-10.5% (42-88 mmol/mol)
Exclusion criteria
are as follows: 1. Diabetes mellitus, type 1 and/or treatment with insulin or sulfonylureas 2. Metal implants, such as a cardiac pacemaker or an aneurysm clip 3. History of any endocrine condition that would affect body weight, such as thyroid disease, pituitary abnormality, or Cushing's syndrome 4. Smoking during the past six months 5. Alcohol consumption of more than 2 drinks per day or the equivalent, episodic increased drinking (e.g., more than 2 drinks per day on weekends), or a history of alcohol abuse or dependency followed by any current use 6. Use of recreational drugs in the past 6 months 7. Use within the preceding six months of medications that affect appetite or body weight, such as estrogens or other hormones, thyroid medications, systemic steroids, antidepressants (tricyclics, MAOIs, SSRIs), antipsychotics, lithium, anticonvulsants, appetite suppressants or other weight-loss drugs, herbs for weight loss or mood, St. John's wort, ephedra, beta blockers 8. Pregnancy or intention to become pregnant during the study period 9. Unstable medical or psychiatric illness 10. Evidence of an eating disorder 11. Likely to be disruptive in group sessions 12. Already following a low-fat, vegan diet 13. Lack of English fluency 14. Inability to maintain current medication regimen 15. Inability or unwillingness to participate in all components of the study 16. Intention to follow another weight-loss method during the trial Participants will also review and complete the Yale MRI Safety Questionnaire to determine eligibility for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of glycemic control | 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44 | Rate of glycemic control will be assessed through HbA1C. |
| Concentration of C-peptide | 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44 | Concentration of C-peptide be assessed during a standard meal test (Boost Plus, Nestle, Vevey, Switzerland; 720 kcal, 34% of energy from fat, 16% protein, 50% carbohydrate). Concentration of C-peptide will be measured at 0, 30, 60, 120, and 180 min. |
| Intramyocellular lipid content | 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44 | Proton magnetic resonance (MR) spectroscopy at 4T (Bruker) will be implemented to quantify intramyocellular lipid concentrations. |
| Hepatocellular lipid content | 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44 | Proton magnetic resonance (MR) spectroscopy at 4T (Bruker) will be implemented to quantify intramyocellular lipid concentrations. |
| Insulin sensitivity | Change from baseline to 22 weeks and change from 22 weeks to 44 weeks | Insulin resistance will be assessed by the Homeostatic Model Assessment (HOMA) PREDIM indexes |
| Concentration of glucose | 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44 | Concentration of glucose will be assessed during a standard meal test (Boost Plus, Nestle, Vevey, Switzerland; 720 kcal, 34% of energy from fat, 16% protein, 50% carbohydrate). Plasma concentrations of glucose will be measured at 0, 30, 60, 120, and 180 min. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body weight | Change from baseline to 22 weeks and change from 22 weeks to 44 weeks | Change in body weight measured on a calibrated scale. |
| Resting energy expenditure | Change from baseline to 22 weeks and change from 22 weeks to 44 weeks | Resting energy expenditure REE (pulse, respiratory rate and body temperature) will be measured for 20 minutes through indirect calorimetry utilizing a ventilated hood system in fasting participants. |
| Postprandial metabolism | Change from Baseline to 22 weeks and change from 22 weeks to 44 weeks | Postprandial metabolism will be measured by indirect calorimetry. Participants will be asked to report to the laboratory within 60 minutes of waking and after a 12-hour fast. Following 30 minutes of quiet rest in a dimly lit room, pulse, respiratory rate, and body temperature will be measured. Resting energy expenditure will be measured for 20 minutes through indirect calorimetry utilizing a ventilated hood system. Postprandial metabolism will be measured four times, 20 minutes each time, over the course of 3 hours after the standard breakfast. |
| Body Composition | Change from baseline to 22 weeks and change from 22 weeks to 44 weeks | Body composition will be measured by dual energy x-ray absorptiometry (Lunar iDXA, GE Healthcare; Madison WI), assessing visceral adipose tissue volume and mass. |
| Gut microbiome composition | Change from baseline to 22 weeks and change from 22 weeks to 44 weeks | Quantitative determination of microorganisms and global analysis of microbial diversity from stool sample. The mean of the change between time points in bacteria counts. |
| Concentration of plasma lipids | Change from baseline to 22 weeks and change from 22 weeks to 44 weeks | Change in plasma cholesterol & triglycerides. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Advanced Glycation Endproducts (AGEs) | 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44 | Advanced Glycation Endproducts (AGEs) will be measured using the AGE Reader mu by Diagnoptics. |
| Endothelial function | 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44 | Endothelial function will be measured through use of the itamar EndoPAT, which quantifies the endothelium-mediated changes in vascular tone elicited by a 5-minute occlusion of the brachial artery. |
Countries
United States
Outcome results
None listed