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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
20
Pre-meal exercise: 1º milkshake intake + 2º exercise test Post-meal exercise: 1º exercise test + 2º milkshake intake Non-exercise meal: Only milkshake intake
University of Graz
Graz, Styria, Austria
Percentage of time spent in the euglycemic range for the 24 hours after each experimental condition
* T1DM non-pregnant women, euglycemic range: 3.9 - 10 mmol/L (70 - 180 mg/dL). * T1DM pregnant women, euglycemic range: 3.5 - 7.8 mmol/L (63 - 140 mg/dL).
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Percentage of time spent in the euglycemic range for the 24 hours after each experimental condition
* 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).
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Percentage of time spent in hypoglycemia for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \< 3.9 mmol/L (\< 70 mg/dL). * T1DM pregnant women - range: \< 3.5 mmol/L (\< 63 mg/dL).
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Percentage of time spent in hypoglycemia for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \< 3.9 mmol/L (\< 70 mg/dL). * T1DM pregnant women - range: \< 3.5 mmol/L (\< 63 mg/dL).
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Percentage of time spent in hyperglycemia for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \> 10 mmol/L (\> 180 mg/dL). * T1DM pregnant women - range: \> 7.8 mmol/L (\> 140 mg/dL).
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Percentage of time spent in hyperglycemia for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \> 10 mmol/L (\> 180 mg/dL). * T1DM pregnant women - range: \> 7.8 mmol/L (\> 140 mg/dL).
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Differences in postprandial glucose levels 1-, 2-, and 4-hours post-experiment
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
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 4 h/day)
Differences in postprandial glucose levels 1-, 2-, and 4-hours post-experiment
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
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 4 h/day)
Number of hypoglycaemic events for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \< 3.9 mmol/L (\< 70 mg/dL). * T1DM pregnant women - range: \< 3.5 mmol/L (\< 63 mg/dL).
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Number of hypoglycaemic events for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \< 3.9 mmol/L (\< 70 mg/dL). * T1DM pregnant women - range: \< 3.5 mmol/L (\< 63 mg/dL).
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Number of hyperglycaemic events for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \> 10 mmol/L (\> 180 mg/dL). * T1DM pregnant women - range: \> 7.8 mmol/L (\> 140 mg/dL).
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Number of hyperglycaemic events for the 24 hours after each experimental condition
* T1DM non-pregnant women - range: \> 10 mmol/L (\> 180 mg/dL). * T1DM pregnant women - range: \> 7.8 mmol/L (\> 140 mg/dL).
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Percentage of time spent in nocturnal euglycemia within each experimental day
* 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).
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 00:00 am - 05:59 am)
Percentage of time spent in nocturnal euglycemia within each experimental day
* 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).
Time frame: 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 )
Percentage of time spent in diurnal euglycemia within each experimental day
* 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).
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 6.00 am - 23:59 am)
Percentage of time spent in diurnal euglycemia within each experimental day
* 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).
Time frame: 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)
Area under the curve of glycaemic exposure
Area under the curve of glycaemic exposure during the 2, 4 and 8 hours after meal intake at each experimental condition.
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 8 hours/day)
Area under the curve of glycaemic exposure
Area under the curve of glycaemic exposure during the 2, 4 and 8 hours after meal intake at each experimental condition.
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 8 h/day)
Glycaemic variability (standard deviation)
Standard deviation (SD) of the mean continuous glucose monitoring levels over the 24 hours after each experimental condition
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Glycaemic variability (standard deviation)
Standard deviation (SD) of the mean continuous glucose monitoring levels over the 24 hours after each experimental condition
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Glycaemic variability (coefficient of variation)
Coefficient of variation of glucose levels over the 24 hours after each experimental condition
Time frame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Glycaemic variability (coefficient of variation)
Coefficient of variation of glucose levels over the 24 hours after each experimental condition
Time frame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Maternal glucose metabolism
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).
Time frame: assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
Maternal glucose metabolism
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).
Time frame: assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
Maternal lipid profile
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).
Time frame: assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
Maternal lipid profile
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).
Time frame: assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
Maternal inflammatory markers
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)
Time frame: assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
Maternal inflammatory markers
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)
Time frame: assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
Placenta weight
Placenta weight (grams)
Time frame: assessed at birth - 30 minutes
Placenta biopsies
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).
Time frame: collected at birth - 1 hour
Neonate weight
Neonate weight (grams)
Time frame: assessed at birth - 5 minutes
Placenta efficiency
Neonate weight divided by placenta weight
Time frame: estimated after birth - 3 minutes
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.