POLY-unsaturated Fatty Acids in the Preservation of Dietary Effects on Hepatosteatosis and Energy Metabolism in Type 2 Diabetes

Study Overview
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Brief Summary
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Basic treatment of type 2 diabetes should focus on diet, physical activity and lifestyle. Nevertheless, in early and late stage of T2DM, lifestyle intervention is mostly substituted by pharmacological intervention, although lifestyle modification and dietary treatment would be favourable. The researchers therefore investigate dietary strategies such as low-carb and very-low calory diets regarding their potential to improve metabolism and body weight in (mostly) long-term T2DM patients. This core comparison is dealt with in the DiNA-D study (published elsewhere). POLYPHEM targets specific dietary approach to preserve the achieved metabolic improvements from DiNA-D phase 1. Nutritional factors will be PUFAs and BCAAs.

Detailed Description
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Basic treatment of type 2 diabetes should focus on diet, physical activity and lifestyle. Nevertheless, in early and late stage of T2DM, lifestyle intervention is mostly substituted by pharmacological intervention, although lifestyle modification and dietary treatment would be favourable. The researchers therefore investigate dietary strategies such as low-carb and very-low calory diets regarding their potential to improve metabolism and body weight in (mostly) long-term T2DM patients. This core comparison is dealt with in the DiNA-D study (published elsewhere). POLYPHEM targets specific dietary approach to preserve the achieved metabolic improvements from DiNA-D phase 1. Nutritional factors for the maintenance period within DiNA-D (11 months) will be PUFAs and BCAAs, provided by walnuts and custom-made muffins containing walnuts, sunflower oil and isomaltulose.

Official Title
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POLY-unsaturated Fatty Acids in the Preservation of Dietary Effects on Hepatosteatosis and Energy Metabolism in Type 2 Diabetes

Conditions
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Type 2 Diabetes, NAFLD, Obesity, Dyslipidemia, Hypertension, Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: diet with/without supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male and female subjects 18-79 years old type 2 diabetes Exclusion Criteria: renal insufficiency anaemia immunosuppression previous symptomatic cancer diagnosis acute cardiovascular disease (stroke, coronary syndrome) pregnancy and lactation severe psychiatric disorders corticoid or other immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: low-carb with PUFA<br>49 weeks of hypo- to isocaloric low-carb diet (< 40 EI% carbs), amplified with walnuts and walnut-sunflower muffins | Dietary Supplement: diet with/without supplementation<br>* diet with/without supplementation with PUFAs<br>|
| Active Comparator: low-carb without PUFA<br>49 weeks of hypo- to isocaloric low-carb diet (< 40 EI% carbs), without walnuts / walnut-sunflower muffins | Dietary Supplement: diet with/without supplementation<br>* diet with/without supplementation with PUFAs<br>|
| Active Comparator: low-fat with PUFA<br>49 weeks of hypo- to isocaloric low-fat diet (< 30 EI% fat), amplified with walnuts and walnut-sunflower muffins | Dietary Supplement: diet with/without supplementation<br>* diet with/without supplementation with PUFAs<br>|
| Active Comparator: low-fat without PUFA<br>49 weeks of hypo- to isocaloric low-fat diet (< 30 EI% fat), without walnuts / walnut-sunflower muffins | Dietary Supplement: diet with/without supplementation<br>* diet with/without supplementation with PUFAs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in insulin secretion (glucagon stimulation test) | change in insulin secretion (glucagon stimulation test) | 49 weeks | 
| change in hepatic fat content (MR-S) | change in hepatic fat content (MR-S) | 49 weeks | 
| change in insulin secretion in the mixed-meal tolerance test (MMTT) - combined parameter | change in insulin secretion in the mixed-meal tolerance test (MMTT) - combined parameter | 49 weeks | 
| change in insulin sensitivity in the mixed-meal tolerance test (MMTT) - combined parameter | change in insulin sensitivity in the mixed-meal tolerance test (MMTT) - combined parameter | 49 weeks | 
| change in blood glucose profile in the mixed-meal tolerance test (MMTT) - combined parameter | change in blood glucose profile in the mixed-meal tolerance test (MMTT) - combined parameter | 49 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inflammatory reaction in subcutaneous adipose tissue (SCAT analysis on protein and RNA level - IL-1; IL1beta, IL-6) | inflammatory reaction in subcutaneous adipose tissue (SCAT analysis on protein and RNA level - IL-1; IL1beta, IL-6) | 49 weeks | 
| change in parameters of peripheral neuropathy - vibration threshold | change in parameters of peripheral neuropathy - vibration threshold | 49 weeks | 
| change in parameters of peripheral neuropathy - thermal sensitivity | change in parameters of peripheral neuropathy - thermal sensitivity | 49 weeks | 
| change in parameters of peripheral neuropathy - pain thresholds | change in parameters of peripheral neuropathy - pain thresholds | 49 weeks | 
| change in parameters of autonomic neuropathy - measures of cardio-autonomic neuropathy (MSDD) | change in parameters of autonomic neuropathy - measures of cardio-autonomic neuropathy (MSDD) | 49 weeks | 
| change in parameters of autonomic neuropathy - measures of cardio-autonomic neuropathy (SANN) | change in parameters of autonomic neuropathy - measures of cardio-autonomic neuropathy (SANN) | 49 weeks |