Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes - Mechanisms of Effective Therapy of Diabetes by Selective Choice of Macronutrients - The Phenotype Study

Study Overview
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Brief Summary
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Scientific evidence for the dietary treatment of type 2 diabetes is insufficient. The investigators hypothesize that a lower carbohydrate content in the diabetic diet than the recommended 55 E% will decrease the postprandial glucose excursion, decrease insulinotropic factors like incretin hormones and decrease their insulinotropic effects due to their glucose dependency. This will reduce postprandial insulin concentration, resulting in an improved insulin sensitivity and glucose metabolism. This clinical study will examine in diabetic, prediabetic and healthy subjects the acute effects of short term highly controlled dietary low carbohydrate intervention on metabolic pathways with respect to insulin action, pancreatic islet function, lipid metabolism, incretin hormones, low grade inflammation in plasma and novel measures of fatty acid metabolism.

Official Title
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Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes - Mechanisms of Effective Therapy of Diabetes by Selective Choice of Macronutrients - The Phenotype Study

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Other: Low carbohydrate meals
* Other: Standard carbohydrate meals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men age 18-70 years Postmenopausal women age 55-70 years Non-smoker (abstinent at least 6 months) HbA1c < 74 mmol/mol Fasting blood glucose < 11 mmol/L (mean of 3 measurements) Negative (<25 IU/L) plasma glutamate decarboxylase (GAD-65) antibodies (IgG) Hemoglobin > 7.5 mmol/L (men); > 6.8 mmol/L (women) Normal thrombocytes (140-400 x 109/L) eGFR > 45 ml/min per 1.73 m2 Alkaline phosphatase < 140 IU/L Alanine aminotransferase < 70 IU/L Normal International Normalized Ratio (0.9-1.2) Exclusion Criteria: Critical illness Anti-diabetic drugs other than metformin (maximum of 2000 mg / day) Steroid treatment e.g. prednisolone Reported or journalized severe food allergy or intolerance Reported or journalized gut disease e.g. Crohn's disease, Coeliac disease Reported or journalized alcohol dependence syndrome

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Type 2 diabetic subjects<br> | Other: Low carbohydrate meals<br>* Meal macronutritional energy composition: Carbohydrate 30% Protein 30% Fat 40%<br>Other: Standard carbohydrate meals<br>* Meal macronutritional energy composition: Carbohydrate 55% Protein 15% Fat 30%<br>|
| Active Comparator: Prediabetic subjects<br> | Other: Low carbohydrate meals<br>* Meal macronutritional energy composition: Carbohydrate 30% Protein 30% Fat 40%<br>Other: Standard carbohydrate meals<br>* Meal macronutritional energy composition: Carbohydrate 55% Protein 15% Fat 30%<br>|
| Active Comparator: Healthy subjects<br> | Other: Low carbohydrate meals<br>* Meal macronutritional energy composition: Carbohydrate 30% Protein 30% Fat 40%<br>Other: Standard carbohydrate meals<br>* Meal macronutritional energy composition: Carbohydrate 55% Protein 15% Fat 30%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Insulin sensitivity as measured by the oral minimal model applied to the meal test | Measured during meal tests (2 days with each intervention) |