Women With Previous GDM and the Effects of HIIT.

N/AEnrolling By InvitationNCT07566845

Odense University Hospital40 enrolled

Overview

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: 1. Women with pGDM have metabolic abnormalities compared with women without pGDM, and that these metabolic abnormalities are explained by unique molecular abnormalities in skeletal muscle and adipose tissue. 2. Eight weeks of HIIT combining rowing and cycling can markedly improve these metabolic abnormalities in women with pGDM and these improvements are explained by beneficial cellular and molecular changes in skeletal muscle and adipose tissue. 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Interventions

High-intensity interval trainingOTHER

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.

Eligibility

Sex: FEMALEMin age: 25 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age 25-45 years * BMI 20-35 kg/m2 * 2-8 years since the last pregnancy * No known diabetes or PCOS * No previous bariatric surgery * No known disease * Be drug-naive * Have a regular menstrual cycle (23-35 days) * Not be pregnant or planning pregnancy during the study period * Low or moderate level of physical activity must be (max 2 hours of moderate exercise weekly). * All participants should be able to provide informed consent * Women without pGDM must not have known hypertension or first-degree relatives with diabetes. Exclusion Criteria: * Abnormal cardiac stethoscopy, ECG or screening blood tests * Positive plasma GAD-65 antibodies * Positive plasma choriogonadotropine * Undiagnosed T2D based on fasting plasma glucose (≥ 7.0 mmol/mol), plasma HbA1c (≥ 48 mmol/mol), or 2-h plasma glucose during an oral glucose tolerance test (OGTT) (≥ 11.1 mmol/mol) * Dyslipidemia (plasma LDL-cholesterol \> 5.0 mmol/l) * In women with pGDM: Undiagnosed severe hypertension (blood pressure \> 160/100) * In women without pGDM: Undiagnosed hypertension (blood pressure \>140/90 mmHg) or impaired glucose tolerance (fasting plasma glucose at 6.16.9 mmol/l, plasma HbA1c at 42-47 mmol/mol, or a 2-h glucose at 7.8-11.0 mmol/l during an OGTT).

Outcomes

Primary Outcomes

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.

Time frame: 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).

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: At examination day 1 and 3.

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).

Time frame: At examination day 2 and 4.

Secondary Outcomes

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.

Time frame: At examination day 2 and 4.

Tissue-specific metabolomics by LC- and GC-MS

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Women With Previous GDM and the Effects of HIIT.

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes