Women With Previous GDM and the Effects of HIIT. (GDM-HIIT)

Deep Metabolic and Molecular Phenotyping of Women With Previous Gestational Diabetes Mellitus and the Responses to High-intensity Interval Training.

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 Overview

• Status: Enrolling by invitation
• Conditions: Type 2 Diabetes (T2DM); Gestational Diabetes Mellitus (GDM); High-intensity Interval Training
• Intervention / Treatment: Other: High-intensity interval training

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Region Syddanmark
    • Odense, Region Syddanmark, Denmark, 5000
      • Steno Diabetes Center Odense, Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Women with previous gestational diabetes mellitus; Women with previous gestational diabetes mellitus, aged 25-45, who gave birth 2-8 years ago.	Other: High-intensity interval training; 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.
Active Comparator: Women without previous gestational diabetes; Women without previous gestational diabetes mellitus, aged 25-45, who gave birth 2-8 years ago.	Other: High-intensity interval training; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.
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.

Secondary Outcome Measures

Outcome Measure	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.
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.

Other Outcome Measures

Outcome Measure	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.	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.

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: University of Southern Denmark
• Investigators: Principal Investigator: Kurt Højlund, Prof. Dr. med., Steno Diabetes Center Odense, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: T2DM; GDM; HIIT
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes, Gestational; Diabetes Mellitus, Type 2; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Physical Conditioning, Human; Exercise; High-Intensity Interval Training
• Other Study ID Numbers: 25/55674

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No