Maternal ExeRcIse Timing to Optimise Postprandial Glucose in Type 1 Diabetes

Not Applicable

Recruiting

• Conditions: Pregnancy in Diabetic; Type 1 Diabetes

• Registration Number: NCT05843175
• Lead Sponsor: University of Graz

Brief Summary

Poor glycaemic control in pregnancy is a major factor leading to obstetric complications and future maternal-offspring diseases. This phenomenon is evidenced in women with type 1 diabetes (T1DM), and is worrisome since it is aggravating the disease burden of this and next generations.

Exercise is a promising tool to improve glucose control during pregnancy and thus avoid adverse consequences.

The MERIT1D study will explore when is exercise (before or after lunch) more effective to improve postprandial glycaemic control in pregnant and non-pregnant women (of reproductive age) with T1DM, and the mechanisms underlying these metabolic responses.

Detailed Description

Poor glycaemic control in pregnancy is a major factor leading to obstetric complications and future maternal-offspring diseases (e.g., macrosomia, diabetes). This phenomenon is evidenced in women with type 1 diabetes (T1DM), and is worrisome since it is aggravating the disease burden of this and next generations. Therefore, to find strategies aimed at breaking this intergenerational cycle has become a high-priority. Exercise is a promising tool to improve short-term glycaemic responses such as postprandial glucose peaks and glucose variability, and thus reduce adverse maternal-neonatal outcomes. However, it is unknown which timing of exercise is more effective to optimise postprandial glycaemic control in pregnant women with T1DM, and non-pregnant women (of reproductive age) with T1DM. The mechanisms underlying these benefits in T1DM and pregnancy are also to be established.

The MERIT1D project will unravel which timing of exercise (before or after a meal at lunchtime) is more effective to optimise postprandial glycaemic control in pregnant and non-pregnant women with T1DM, and the mechanisms underlying these metabolic responses. Ten pregnant women with T1DM and ten non-pregnant women with T1DM will be involved in this randomised controlled crossover trial.

Pregnant women at gestational week 16 and 35 (experimental phases 1 and 2, respectively), and non-pregnant peers once after recruitment (experimental phase 1), will undergo 3 experimental conditions within 10 days (random order): pre-meal exercise, post-meal exercise, and non-exercise meal.

Each experimental phase will entail participants attending 4 times to the research centre. Therefore, pregnant women will come to the research centre for a total of 8 study visits, while non-pregnant women will come only to 4 study visits. The acute exercise stimulus will consist of a well-controlled submaximal walking test. The standardised meal provided will consist of a mixed milkshake equivalent to the 35 % of their resting energy expenditure, being made up of approximately 45% carbohydrates, 35% fat, and 20% proteins. Postprandial glycaemic responses will be continuously monitored using last-generation glucose monitoring systems during the 10-day period. Immunometabolic markers (e.g., lipids, cytokines) will be determined in maternal blood and placenta samples.

The MERIT1D study will contribute to the understanding of exercise timing in T1DM and pregnancy, and its underlying mechanisms. This will translate into a better clinical prediction, diagnosis, prognosis and treatment of glycaemic dysregulations, and into more effective exercise programmes for pregnant and non-pregnant women with T1DM.

Study Timeline

• Study First Submitted: 2023-03-27
• Study First Submitted QC: 2023-04-24
• Study First Posted: 2023-05-06
• Study Start: 2023-06-22
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-11
• Last Update Posted: 2024-03-12
• Primary Completion: 2024-09-24
• Study Completion: 2025-04-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

• Pregnant women and non-pregnant women with T1DM aged 20-40 years
• Having a BMI of 18-29.9 kg/m2 at pre-pregnancy (pregnant women) or recruitment (non-pregnant)
• Clinical diagnosis of T1DM, or/and multiple daily insulin injections for >1 year, and/or using insulin pump therapy (open-loop).
• Willingness to provide informed consent to participate in the MERIT1D study.
• Being able to read and speak German, English or Spanish well enough to completely understand the instructions, provide informed consent and conduct the experimental procedures.

Exclusion Criteria

• Having poor glycaemic control HbA1c>10% (86 mmol/mol).
• Recurrent severe hypoglycaemia; hospitalisation for diabetic ketoacidosis during the last year.
• Women who smoke or drink alcohol frequently, or require complex diets.
• Having polycystic ovarian syndrome, poorly controlled asthma/allergy, uncontrolled thyroid diseases or hypertension, diabetic ketoacidosis, hepatitis B, hepatitis C, HIV.
• Having severe autoimmune/immunodeficiency, macrovascular, renal, or neuromuscular disease, or severe retinopathy or neuropathy.
• Having any other cardiovascular, pulmonary, orthopaedic, neurologic, psychiatric, or terminal disease, or any other acute/chronic disorder that, in the opinion of the local clinician/researcher, would preclude participation and successful completion of the protocol, or that would directly influence the study results.
• Use of any medication (e.g., steroids), that, in the opinion of local clinician/researcher, would negatively impact or mitigate full participation and completion, or could influence the study results.
• Any condition that would interfere with compliance or the results, as judged by the Investigator
• Pregnant women: having multiple pregnancy
• Pregnant women: evidence of incompetent cervix, ruptured membranes, placenta previa, foetal malformation, or foetal death.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Percentage of time spent in the euglycemic range for the 24 hours after each experimental condition	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)	* T1DM non-pregnant women: 3.9 - 10 mmol/L (70 - 180 mg/dL).; * T1DM pregnant women: 3.5 - 7.8 mmol/L (63 - 140 mg/dL).

Secondary Outcome Measures

Name	Time	Method
Percentage of time spent in hyperglycemia for the 24 hours after each experimental condition	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)	* T1DM non-pregnant women - range: \> 10 mmol/L (\> 180 mg/dL).; * T1DM pregnant women - range: \> 7.8 mmol/L (\> 140 mg/dL).
Percentage of time spent in diurnal euglycemia within each experimental day	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 6.00 am - 23:59 am)	* T1DM non-pregnant women - range: euglycemia 3.9 - 10 mmol/L (70 - 180 mg/dL).; * T1DM pregnant women - range: euglycaemia 3.5 - 7.8 mmol/L (63 - 140 mg/dL).
Area under the curve of glycaemic exposure	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 8 h/day)	Area under the curve of glycaemic exposure during the 2, 4 and 8 hours after meal intake at each experimental condition.
Placenta biopsies	collected at birth - 1 hour	Eight biopsies will be collected, four on the maternal site and four on the fetal side. Relevant placental proteins (growth factors and cytokines) related to insulin signalling, glucose metabolism, and inflammation will be analysed (e.g., GM-CSF, GCSF, MCP1, TNF-α, IL-6, EGF, IFN-γ, IL-8, IL-10, IL-1β).
Number of hyperglycaemic events for the 24 hours after each experimental condition	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)	* T1DM non-pregnant women - range: \> 10 mmol/L (\> 180 mg/dL).; * T1DM pregnant women - range: \> 7.8 mmol/L (\> 140 mg/dL).
Glycaemic variability (coefficient of variation)	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)	Coefficient of variation of glucose levels over the 24 hours after each experimental condition
Maternal glucose metabolism	assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to the glucose-insulin axis will be analysed (i.e., glucose, insulin, C-peptide and HbA1c).
Maternal lipid profile	assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to the lipid profile will be analysed (i.e., total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL-cholesterol, triglycerides and free fatty acids).
Placenta weight	assessed at birth - 30 minutes	Placenta weight (grams)
Neonate weight	assessed at birth - 5 minutes	Neonate weight (grams)
Percentage of time spent in hypoglycemia for the 24 hours after each experimental condition	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)	* T1DM non-pregnant women - range: \< 3.9 mmol/L (\< 70 mg/dL).; * T1DM pregnant women - range: \< 3.5 mmol/L (\< 63 mg/dL).
Differences in postprandial glucose levels 1-, 2-, and 4-hours post-experiment	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 4 h/day)	Within-change in glucose values (mmol/L) from pre-experiment (before starting exercise/meal testing) to post-experiment (i.e., 1-, 2-, and 4-hours after starting exercise/meal intake) in each experimental day
Placenta efficiency	estimated after birth - 3 minutes	Neonate weight divided by placenta weight
Percentage of time spent in nocturnal euglycemia within each experimental day	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 00:00 am - 05:59 am )	* T1DM non-pregnant women - range: euglycemia 3.9 - 10 mmol/L (70 - 180 mg/dL).; * T1DM pregnant women - range: euglycaemia 3.5 - 7.8 mmol/L (63 - 140 mg/dL).
Glycaemic variability (standard deviation)	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)	Standard deviation (SD) of the mean continuous glucose monitoring levels over the 24 hours after each experimental condition
Maternal inflammatory markers	assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to inflammatory-immunological responses will be analysed (e.g., IL-6, IL-8, IL-1β, TNFα, C-reactive protein, IFNγ)
Number of hypoglycaemic events for the 24 hours after each experimental condition	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)	* T1DM non-pregnant women - range: \< 3.9 mmol/L (\< 70 mg/dL).; * T1DM pregnant women - range: \< 3.5 mmol/L (\< 63 mg/dL).

Trial Locations

Locations (1)

University of Graz; 🇦🇹 Graz, Styria, Austria