Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Southern Denmark | OTHER |
Not provided
Not provided
Not provided
Not provided
The goal of this clinical trial is to investigate if women with previous gestational diabetes (pGDM) are characterized with unique metabolic and molecular alterations compared to women without pGDM. Furthermore if 8 weeks of high-intensity interval training (HIIT) can improve these alterations. The main questions we aim to answer are:
Researchers will compare 20 women with pGDM to 20 glucosetolerant without pGDM, who are matched on age, BMI and times since last pregnancy.
Participants will undergo a screening visit and examinations on two separate days before (day 1 and day 2) and two separate days after (day 3 and day 4) 8-weeks of HIIT, in all cases after an overnight fast (≥ 12 h). Day 1 and day 3 will include assessment of body composition and VO2max. On day 2 and day 4, the insulin sensitivity, substrate metabolism, and β-cell function of the participants will be examined by a Botnia-clamp combined by indirect calorimetry. Skeletal muscle biopsies from m. vastus lateralis and subcutaneous abdominal adipose tissue biopsies are taken in the basal and insulin-stimulated states of each clamp.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Women with previous gestational diabetes mellitus | Experimental | Women with previous gestational diabetes mellitus, aged 25-45, who gave birth 2-8 years ago. |
|
| Women without previous gestational diabetes | Active Comparator | Women without previous gestational diabetes mellitus, aged 25-45, who gave birth 2-8 years ago. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High-intensity interval training | Other | The training intervention consists of 8-weeks of HIIT combining rowing and cycling on ergometers with two supervised sessions weekly in small groups of up to 10 participants. All HIIT sessions will start with a 10-min warm-up period followed by training blocks of 5 x 1 min high-intensity intervals (100-110% of Wattmax corresponding to ≥ 85% of maximum heart rate (HRmax)) each interspersed by 1 min active or resting recovery. Between the training blocks, the participants will have a 4-min break in which they shift from cycling to rowing or vice versa. The number of training blocks will gradually increase from two to five blocks during the 8-week intervention period with one block being added every second week. Halfway through the HIIT-protocol the workload will be adjusted according to a midway VO2max test. Participants will wear a heart monitor during training sessions. |
| Measure | Description | Time Frame |
|---|---|---|
| β-cell function by OGTT | Will be estimated as the disposition index (DI) by oral glucose tolerance test (OGTT) derived indices of insulin sensitivity and insulin secretion, after a 2-hour OGTT (75g) with measurement of plasma glucose, serum insulin and serum C-peptide at 0, 30 and 120 min. | At screening visit. |
| β-cell function by Botnia-clamp | β-cell function adjusted for insulin sensitivity will be determined by calculating the DI as a product of the acute insulin response to glucose (AIRg) and insulin-stimulated glucose infusion rate (GIR). | At examination day 2 and 4. |
| Whole body composition (lean body mass and fat mass) | Will be obtained by a dual-energy X-ray absorptiometry (DXA) scanning (Prodigy Advance, GE Healthcare, CHI, US) | At examination day 1 and 3. |
| Lean body mass | Will be obtained by a dual-energy X-ray absorptiometry (DXA) scanning (Prodigy Advance, GE Healthcare, CHI, US) | At examination day 1 and 3. |
| Fat mass | Will be obtained by a dual-energy X-ray absorptiometry (DXA) scanning (Prodigy Advance, GE Healthcare, CHI, US) | At examination day 1 and 3. |
| Cardiorespiratory fitness (maximal oxygen consumptions (VO2-max)) | Will be determined by an incremental exercise test on a cycle ergometer (SRM Ergometer System, Jülich, DE) combined with mixed chamber cardiopulmonary exercise analyzer (Oxigraf, Model O2CPX, California, US) | At examination day 1 and 3. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma-specific metabolomics by LC- and GC-MS | Liquid chromatography (LC)- and gas chromatography (GS)-based mass spectrometry (MS) will be used to detection, identification, and quantitation of very large numbers of metabolites in the micro- and nano-molar range in body fluids, such as blood. | At examination day 2 and 4. |
| Measure | Description | Time Frame |
|---|---|---|
| Lipid profile | Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, non-HDL-cholesterol and triglycerides determined by blood tests. | At examination day 2 and 4. |
| HbA1c | Determined by blood tests. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kurt Højlund, Prof. Dr. med. | Steno Diabetes Center Odense, Odense University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Steno Diabetes Center Odense, Odense University Hospital | Odense | Region Syddanmark | 5000 | Denmark |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D016640 | Diabetes, Gestational |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003920 | Diabetes Mellitus |
Not provided
Not provided
| ID | Term |
|---|---|
| D000072696 | High-Intensity Interval Training |
| ID | Term |
|---|---|
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
Not provided
Not provided
Both groups will undergo same examinations and training-intervention.
Not provided
Not provided
Not provided
Not provided
|
| Insulin sensitivity by Botnia-clamp | Consisting of a hyperinsulinemic-euglycemic clamp (insulin 40mU/min/m2 for 3 h) combined with a 60 min intravenous glucose tolerance test (IVGGT) using a glucose bolus (0.3 kg per kg body weight with a maximum of 25 g glucose). | At examination day 2 and 4. |
| Tissue-specific metabolomics by LC- and GC-MS |
Liquid chromatography (LC)- and gas chromatography (GS)-based mass spectrometry (MS) will be used to detection, identification, and quantitation of very large numbers of metabolites in the micro- and nano-molar range in body tissues. |
| At examination day 2 and 4. |
| Proteomics | To identify biological processes and signaling networks altered in women with pGDM and changed in response to HIIT, we will apply unbiased mass-spectrometry based proteome analysis of the skeletal muscle and adipose tissue biopsies. | At examination day 2 and 4. |
| Phosphoproteomics | To identify biological processes and signaling networks altered in women with pGDM and changed in response to HIIT, we will apply unbiased mass-spectrometry based phosphoproteome analysis of the skeletal muscle and adipose tissue biopsies. | At examination day 2 and 4. |
| Transcriptional profiling and gene expression | High-resolution transcriptional profiling of abdominal adipose tissue and skeletal muscle biopsies will be performed using total RNA sequencing with next generation sequencing (TruSeq® Stranded Total RNA Library Prep Gold; Illumina). Gene expressions are quantified using Targeted quantitative real-time PCR (qRT-PCR) and Western Blotting. | At examination day 2 and 4. |
| Mitochondrial respiration | Will be measured on permeabilized muscle fibers, and analyzed by measuring oxygen consumption when adding substrates, uncouplers, and inhibitors to the chambers of a high-resolution oxygraphy. | At examination day 2 and 4. |
| Lipid droplets by TEM | The morphology, volume, and localization of lipid droplets in muscle biopsies from the study cohorts will be determined by Transmission Electron Microscopy (TEM). | At examination day 2 and 4. |
| Mitochondria by TEM | The morphology, volume, and localization of mitochondria in muscle biopsies from the study cohorts will be determined by Transmission Electron Microscopy (TEM). | At examination day 2 and 4. |
| Lipid droplet interaction with mitochondria by TEM | The the physical interaction between lipid droplets and mitochondria in muscle biopsies from the study cohorts will be determined by Transmission Electron Microscopy (TEM). | At examination day 2 and 4. |
| Protein abundance | Protein abundance will be studied in skeletal muscle and adipose tissue biopsies by Western blotting procedures. | At examination day 2 and 4. |
| Phosphorylation of enzymes | Phosphorylation of enzymes will be studied in skeletal muscle and adipose tissue biopsies by Western blotting procedures. | At examination day 2 and 4. |
| At examination day 2 and 4. |
| Insulin | Determined by blood tests. | At examination day 2 and 4. |
| Glucose | Determined by blood tests. | At examination day 2 and 4. |
| C-peptide | Determined by blood tests. | At examination day 2 and 4. |
| Levels of systemic low-grade inflammation | Circulating levels of adiponectin, leptin, interleukin-6 (IL-6), fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4) and growth differentiation factor 15 (GDF15) will be measured in bloodsamples. | At examination day 2 and 4. |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D009142 |
| Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |