LoBAG30 Diet in Patients on Metformin

Study Overview
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Brief Summary
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We will determine the metabolic response to a Low Biologically Available Glucose Diet (LoBAG30) in subjects currently receiving the maximum dose of metformin as monotherapy in whom the glycohemoglobin is not at an acceptable level (>8.0%). Our hypothesis is that introduction of a LoBAG30 diet to subjects currently treated with a full therapeutic dose of metformin will improve blood glucose control in people who have not achieved an acceptable total glycohemoglobin on metformin alone.

Detailed Description
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Subjects will ingest a control diet (55% carbohydrate (CHO), 15% protein, 30% fat) or a LoBAG30 diet (30% CHO, 30% protein, 40% fat) in a parallel design with block randomization in pairs of two. Subjects will return to the study center twice each week while on the diets to have blood glucose, glycohemoglobin, lactate, weight and blood pressure measured, and to have urine assayed for urea and creatinine. At the beginning and end of the 5 week study period, the subjects will be admitted to the study center for 28 hours during which time blood will be drawn for 24 hour profiles of glucose, insulin, other hormones and several metabolites. For those subjects randomized to the LoBAG30 arm of the study, the control diet will be given during the first 24 hour study period; the assigned diet will be given at the end of the 5 week period.

Official Title
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Metabolic Response to a LoBAG30 Diet in Diabetic Patients on Metformin

Conditions
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Diabetes Mellitus, Diet

Intervention / Treatment
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* Other: LoBAG30 diet
* Other: Control Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: People with type 2 diabetes mellitus who currently are receiving the maximal dose of metformin monotherapy (2500 mg/day). These subjects will have had a stable glycohemoglobin (tGHb) in an unacceptably high range (8-11%) for at least 4 months prior to beginning the study. Subjects with tGHB > 11% (HbA1c > 10%) will not be recruited into the study. Exclusion Criteria: Hematological abnormalities liver disease kidney disease macroalbuminuria (>300 mg albumin/24 hours) untreated thyroid disease congestive heart failure angina life-threatening malignancies proliferative retinopathy severe diabetic neuropathy peripheral vascular disease serious psychological disorders a body mass index > 35 and a fasting triglyceride of >400 mg/dl. Subjects taking slow-release metformin will not be studied. Subjects taking medications other than metformin, known to affect fuel metabolism such as: insulin the sulfonylureas glucagon-like peptide 1 (GLP-1) analogs and metabolic inhibitors pramlintide prednisone and similar steroids thyroid hormone antipsychotic medications thiazide diuretics medroxyprogesterone high dose aspirin, also will be excluded. If concentrations of serum folate, B12 or iron are low, the subject will be excluded from the study until corrected, i.e. until normal concentrations are recorded.

Ages Eligible for Study
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Minimum Age: 50 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>A LoBAG30, weight maintenance diet will be given to subjects on metformin. All food will be provided for 5 weeks. | Other: LoBAG30 diet<br>* A LoBAG30 diet consists of 30% of total energy intake as carbohydrate, 30% protein, and 40% fat.<br>|
| Placebo Comparator: Arm 2<br>A weight maintenance, control diet consisting of 55% carbohydrate, 15% protein, 30% fat will be given to subjects on metformin. All food will be provided for 5 weeks. | Other: Control Diet<br>* A control diet consists of 55% of total energy intake as carbohydrate, 15% protein, 30% fat<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in %Hemoglobin A1c at 5 Weeks From Baseline | Hemoglobin A1c measured before and after 5 weeks on the diet | Baseline and 5 weeks after dietary intervention | 
| Change in Total Glucose Area at 5 Weeks From Baseline | The area response is measured using zero as baseline. The area is measured before dietary intervention, and following 5 weeks of dietary intervention. | Baseline and 5 weeks after dietary intervention | 
| Change in Body Weight at 5 Weeks From Baseline | Subjects were to remain weight stable. We expected less than 2 pound weight change over 5 weeks. Weight was measured before dietary intervention, and after 5 weeks of dietary intervention. | baseline and 5 weeks after dietary intervention | 
| Change in Overnight Fasting Glucose Concentration at 5 Weeks From Baseline | Overnight fasting glucose concentration was measured before dietary intervention and after 5 weeks of dietary intervention. | baseline and 5 weeks after dietary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microalbumin Excretion | change in urinary albumin excretion was measured before dietary intervention and after 5 weeks of dietary intervention | baseline and 5 weeks after dietary intervention | 
| Change in Fasting Triglycerides at 5 Weeks From Baseline | Overnight fasting triglycerides concentration was measured before dietary intervention and after 5 weeks of dietary intervention | baseline and 5 weeks after dietary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus (type 2), Diet, Glycohemoglobin, Lipids, Kidney Function, Glycemic Index, Dietary Protein, Dietary Carbohydrate