Women With Previous GDM and the Effects of 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.

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).