Contrasting Ketogenic and Mediterranean Diets in Individuals With Type 2 Diabetes and Prediabetes: The Keto-Med Trial

Study Overview
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Brief Summary
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The objective of this study is to compare two metabolically distinct diets, WFKD vs Med-Plus, in order to examine the potential benefits, and unintended consequences, of going beyond a focus on maximally avoiding added sugars and refined grains, to also avoiding legumes, fruits, and whole grains.

Detailed Description
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The proposed randomized clinical trial will investigate differential population-specific effects of two low-carbohydrate (low-carb) diet patterns, addressing a gap in the evidence base in this area that will lead to 1) improved treatment strategies for common adverse clinical conditions, 2) improved health for these individuals, and 3) long-term decreases in health care costs. This impactful research will advance the field of personalized and precision medicine.

Official Title
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Contrasting Ketogenic and Mediterranean Diets in Individuals With Type 2 Diabetes and Prediabetes: The Keto-Med Trial

Conditions
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Diabetes Mellitus, Type 2, PreDiabetes

Intervention / Treatment
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* Behavioral: Mediterranean Diet (Med-Plus)
* Behavioral: Well-Formulated Ketogenic Diet (WFKD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 Diagnosed with type 2 diabetes mellitus, OR prediabetes (defined as HbA1c </= 5.7% OR Fasting Glucose of >100 mg/dL) Identify exclusion criteria. Weight < 110 lb BMI > 40 LDL-C >190 mg/dL Blood pressure: SBP > 160 mmHg OR DBP: > 90 mmHg Exclusion Criteria: Weight < 110 lb BMI ≥ 40 LDL-C >190 mg/dL Systolic blood pressure (SBP) > 160 mmHg OR Diastolic blood pressure (DBP) > 90 mmHg Diagnosed with type 1 diabetes or history of ketoacidosis Uncontrolled and untreated diabetes (by discretion of study physician) Active cardiovascular disease (in past year with myocardial infarction, coronary stent or bypass surgery) Kidney disease (eGFR less than 50 mL/min per 1.73 m2) Liver disease (liver transaminase higher than 3 times the normal range for the laboratory) Symptomatic gallstones History of bariatric surgery Anemia Taking any of the following medications in past 3 months: SGLT-2 inhibitors, GLP-1 receptor agonist, Insulin, Amylin analog, Alpha-glucosidase inhibitor, Dopamine agonist, Bile acid sequestrant. Taking any medications for weight loss History of active cancer in the past 3 years except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet. Recent history of chronic excessive alcohol consumption defined as more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day; or > 14 drinks/week. Women: Pregnant currently or planning to become pregnant during the course of the study, and/or breastfeeding Regular/frequent use of smoking or chewing tobacco, e-cigarettes, cigars or other nicotine-containing products Regular use of prescription opiate pain medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 40 adults will be randomized in cross-over design to a Ketogenic or Mediterranean diet for 12 weeks each (no washout) with a 1 month follow-up at the end of the second phase.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mediterranean Diet (Med-Plus)<br>Participants will follow a Mediterranean-type diet (Med-Plus) for 12 weeks. This diet will maximize the intake of vegetables, legumes, fruits and nuts, whole intact grains/cereals and fish; and minimize the intake of meat, poultry, and dairy. It will exclude added sugars and refined grains. | Behavioral: Mediterranean Diet (Med-Plus)<br>* Participants will follow the Med-Plus diet for 12 weeks, then switch to the alternate diet for another 12 weeks (no washout period).<br>|
| Experimental: Well-Formulated Ketogenic Diet (WFKD)<br>Participants will follow a Well-Formulated Ketogenic Diet (WFKD) for 12 weeks. This diet will maximize the intake of non-processed beef, pork, and poultry (preferably organic/grass-fed), fish, heavy cream, low-lactose, high-fat cheeses, animal fats, oils (avocado, coconut, or other nut oils), non-starchy (above ground) vegetables and limited amounts of some fruits (berries). It will exclude legumes, grains, sugars, starchy (below ground) vegetables, most fruits, and polyunsaturated oils (soy, sunflower, peanut, cottonseed, canola, etc.). It will aim for an intake of 20 g of carbohydrates/day at start, with the goal to have no more than 50 grams/day to maintain ketosis. | Behavioral: Well-Formulated Ketogenic Diet (WFKD)<br>* Participants will follow the WFKD diet for 12 weeks, then switch to the alternate diet for another 12 weeks (no washout period).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c (HbA1c) | Change from baseline in HbA1c at 12 weeks of each phase | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiota composition | Change from baseline in alpha diversity at 12 weeks of each phase. We will be using number of observed sequence variants (species) determined by standard 16S rRNA amplicon sequencing (V3-V5 region followed by DADA2 to define error-corrected sequence variants) as our primary metric of alpha diversity. Higher alpha diversity is better. The units are the # of sequence variants. | Baseline and 12 weeks | 
| Microbiota function | Change from baseline in composite of short-chain fatty acids (SCFA) concentration (ug/g stool: acetate + propionate + butyrate) at 12 weeks of each phase. | Baseline and 12 weeks | 
| LDL Cholesterol | Change from baseline in LDL cholesterol at 12 weeks of each phase. | Baseline and12 weeks | 
| HDL Cholesterol | Change from baseline in HDL cholesterol at 12 weeks of each phase. | Baseline and 12 weeks | 
| Triglycerides | Change from baseline in triglycerides at 12 weeks of each phase. | Baseline and 12 weeks | 
| Fasting insulin | Change from baseline in fasting insulin at 12 weeks of each phase. | Baseline and 12 weeks | 
| Blood pressure | Change from baseline in blood pressure at 12 weeks of each phase. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketogenic diet, Mediterranean diet, Diabetes, Prediabetes