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| Name | Class |
|---|---|
| Yale University | OTHER |
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Type 2 diabetes is the most common metabolic disease worldwide, characterized by hyperglycemia, decreased whole body insulin sensitivity, and white adipose tissue (WAT) dysfunction. A key factor in its development is chronic overnutrition, usually with a high-fat diet (HFD), leading to disturbances of glucose and lipid metabolism. However, the mechanism of short-term HFD-induced tissue-specific insulin resistance remains poorly understood. This project aims to further unravel the underlying mechanisms of short-term HFD overnutrition-mediated WAT insulin resistance. The model described here corresponds to a randomized, single- blinded parallel-grouped trial, consisting of two interventions: a macronutrient-balanced diet and or a hypercaloric diet over three weeks in order to investigate differences in interorgan fatty acid and glucose metabolism between the studied groups. Based on recent studies, the hypothesis is that 21-day hypercaloric HFD induces WAT insulin resistance via a diacylglycerol, novel protein kinase C-insulin receptor signaling model in both fasting and insulin-stimulated states.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-fat overnutrition | Active Comparator | Lipid overnutrition: 40% higher lipid consumption per day than required over three weeks. |
|
| Normocaloric macronutrient-balanced nutrition | Active Comparator | Normocaloric, macronutrient-balanced nutrition per day over three weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High-fat overnutrition | Behavioral | Overnutrition: 40% higher lipid consumption per day than required |
|
| Measure | Description | Time Frame |
|---|---|---|
| Whole-body insulin sensitivity and WAT insulin sensitivity | Hyperinsulinemica-euglycemia clamp tests with deuterated glucose to measure fasting and insulin-stimulated whole-body insulin sensitivity and measurement of the index ADIPO-IR (fasting insulin x free fatty acid concentration) before and after dietary intervention period. | 3 weeks intervention period each |
| Measure | Description | Time Frame |
|---|---|---|
| WAT insulin signaling pathways | Adipose tissue biopsies are planned to be taken during the fasting and insulin-stimulated state before and after the dietary intervention period. DAG and ceramide subcellular fractionation assay is planned to be performed. Expressionanalyses for activation /membrane translocation of novel and atypical protein kinase C isoforms will be done. Determination of the degree of phosphorylation of various components of the insulin pathway via Western blot are planned. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Theresia Sarabhai, MD | Contact | 0173-9473478 | DDZ | theresia.sarabhai@ddz.de |
| Sabine Kahl, MD | Contact | 0221-3382- | 698 | sabine.kahl@ddz.de |
| Name | Affiliation | Role |
|---|---|---|
| Michael Roden, Prof., MD | German Diabetes Center | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Georgia Xourafa | Recruiting | Düsseldorf | North Rhine-Westphalia | 40225 | Germany |
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| Normocaloric macronutrient-balanced nutrition | Behavioral | Normocaloric, macronutrient-balanced nutrition: Calories requirement for weight maintenance [(kcal/d) 55% carbohydrates, 15% proteins, 30% fat] |
|
| 3 weeks intervention time |