Treatment of Type 2 Diabetes With Ketogenic Diet

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of ketogenic diet (KD) complete meal replacement treatment of obesity-related Type 2 diabetes mellitus (T2DM) and of obesity in patients with obesity and T2DM. This will be an open-label single arm study evaluating glycemic control and weight loss in obese participants with type 2 diabetes treated for 6 months with 3:1 [fat]:[protein+carbohydrate] ratio, 1600 kcal/day diet.

Detailed Description
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The purpose of the study is to evaluate the efficacy and safety of ketogenic diet (KD) complete meal replacement treatment of obesity-related Type 2 diabetes mellitus (T2DM) and of obesity in patients with obesity and T2DM. This will be an open-label single arm study evaluating glycemic control and weight loss in obese participants with type 2 diabetes treated for 6 months with 3:1 [fat]:[protein+carbohydrate] ratio, 1600 kcal/day diet. Treatment will consist of KD complete meal replacement with 3:1 [fat]: [protein + carbohydrate] weight ratio, and with 1600 kcal restriction. It will consist of pre-made meals, including breakfast, lunch, dinner and two snacks, one each between breakfast and lunch and lunch and dinner. Meals will be made according to supplied recipes (Anemone, LLC.) with a 3-week long meal plan consisting of different recipes for the 3 meals and 2 snacks different for each day of the 3-week cycle, with repeating cycles. All KD-treated participants will receive the same meal plan. Meals will be prepared uniformly by one facility and will be delivered to participants frozen once a week in packages subdivided into individual days with each day's package containing 5 separately packaged meals. Participants will be given a list of allowed 0 calories drinks and will consume no non-allowed beverages. Reductions to oral glycemic medications will occur at the start of the diet. Participants will be evaluated in face-to-face visit during weeks 1, 2 and 4 of the study, then monthly (see Table 1, visit schedule). Evaluations will include weight, BMI, BP, waist circumference, adverse events and treatment compliance. Participants will check their blood glucose levels 3x/day, including am fasting, mid-day and evening 2 hours post-prandial, and urine for ketones levels with Ketostix (Bayer AG, IN, U.S.A.) 2x/day. They will record results in a glucose and ketone level diary which will be reviewed at each visit. Laboratory evaluations will include 8 am serum fasting glucose, insulin levels, C-peptide and lipid panel, HbA1C, serum beta-hydroxybutyrate (BOH), leptin levels, C-reactive protein (CRP), complete blood count (CBC), basic metabolic profile (BMP), renal and liver functions tests (LFTs), and uric acid. Laboratory evaluations will be obtained once at baseline prior to treatment initiation, at 3 and 6 months after treatment initiation. Hunger will be evaluated with a 7-point Likert scale (range: extremely hungry to extremely full) which will be administered at each visit.

Official Title
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Evaluation of Efficacy and Safety of Ketogenic Complete Meal Replacement as Treatment of Obesity-related Type 2 Diabetes Mellitus

Conditions
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Type2 Diabetes Mellitus, Obesity

Intervention / Treatment
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* Other: 3:1 ratio Ketogenic diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 Ability and willingness to sign informed consent form. T2D with BMI ≥ 30 kg/m2 Stable hypoglycemic medications for at least 2 months Exclusion Criteria: History of bariatric surgery ≤ 2 years prior to enrollment. Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, unstable metabolic or endocrine disturbances, renal or liver disease, past history of renal calculi, hyperuricemia, hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism, porphyria, and active systemic cancer. History of uncontrolled hyperlipidemia Change in the dose or type of hypoglycemic treatment within 1 month prior to enrollment. Psychosis within six months of enrollment, evidenced by treatment with anti-psychotic medications with recent medication initiation or dose increase. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements; History of cerebrovascular disease or unstable heart disease within 6 months of enrollment Pregnancy Use of any investigational drugs within 3 months of enrollment. Inability or unwillingness of subject to give written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: 3:1 Ketogenic Complete Meal Replacement<br>Evaluating glycemic control and weight loss in obese participants with type 2 diabetes treated for 6 months with 3:1 [fat]:[protein+carbohydrate] ratio, 1600 kcal/day complete meal replacement ketogenic diet | Other: 3:1 ratio Ketogenic diet<br>* Type 2 Diabetic subjects with BMI greater than or equal to 30 are started on 3:1 ratio ketogenic complete meal replacement program and weight loss and glycemic control is tracked over 6 month intervention period<br>* Other names: Classic Ketogenic Diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type 2 diabetes remission | Defined as normal fasting blood glucose (<126), normal HbA1C (<6.4%), and no diabetic medications | 6 months (study duration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in glucose blood level in patients with type 2 DM in 6 months. | Defined as normal fasting blood glucose (<126), normal HbA1C (<6.4%), and no diabetic medications | 6 months (study duration) | 
| Percentage of diabetic medication load reduction | Change in diabetic medication load | 6 months (study duration) | 
| Change from baseline in HbA1C in patients with type 2 DM in 6 months. | HbA1C | 0, 3 and 6 months treatment duration | 
| Adverse events | Adverse events occurrence | 6 months (study duration) | 
| Fasting serum insulin | Change in fasting serum insulin value | 0, 3 and 6 months treatment duration | 
| BMI | Change BMI from baseline | Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6 | 
| Weight | Change weight from baseline | Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6 | 
| Waist circumference | Change waist circumference from baseline | Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6 | 
| Blood pressure | Change of systolic and diastolic blood pressures from baseline | Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6 | 
| Urine ketone levels | Urine ketone levels evaluation | Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6 | 
| Fasting leptin levels | Fasting leptin levels evaluation | 0, 3 and 6 months treatment duration | 
| Fasting lipid levels | Fasting lipid levels evaluation | 0, 3 and 6 months treatment duration | 
| Hunger scale scores | Likert scale (range: extremely hungry to extremely full) which will be administered at each visit.The best outcome is 5=satisfied. | Day 0, Day 7, Day 14, Month 1, 2, 3, 4, 5 and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketogenic diet, low carb diet, type 2 diabetes, diabetes, weight loss, obesity, diet treatment, nutrition, BMI