Treatment of Type 2 Diabetes With Ketogenic Diet

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.

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.

Eligibility Criteria:
Inclusion Criteria:

1. Age 18-70
2. Ability and willingness to sign informed consent form.
3. T2D with BMI ≥ 30 kg/m2
4. Stable hypoglycemic medications for at least 2 months

Exclusion Criteria:

1. History of bariatric surgery ≤ 2 years prior to enrollment.
2. 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.
3. History of uncontrolled hyperlipidemia
4. Change in the dose or type of hypoglycemic treatment within 1 month prior to enrollment.
5. Psychosis within six months of enrollment, evidenced by treatment with anti-psychotic medications with recent medication initiation or dose increase.
6. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
7. History of cerebrovascular disease or unstable heart disease within 6 months of enrollment
8. Pregnancy
9. Use of any investigational drugs within 3 months of enrollment.
10. Inability or unwillingness of subject to give written informed consent.