Clinical trial NCT02417090: Late Metabolic Effects of Metformin Therapy in Gestational Diabetes
Official title: Metformin Therapy for Gestational Diabetes - Metabolic Late Effects on Child at 9 Years of Age
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gestational Diabetes
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Oulu University Hospital
First posted: 2015-04-15
Enrollment: 173
Sex: ALL
Minimum age (years): 9
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 9-year old children exposed to insulin or metformin in utero because their mothers had gestational diabetes

Brief summary: Metformin in widely used as the treatment of gestational diabetes. However, it is not known whether exposure to metformin in utero has late metabolic effects on the child.

In this study the investigators investigate metabolism (oral glucose tolerance test, insulin, plasma lipoproteins, inflammation markers as well as body composition by DEXA (dual energy X-ray absorption) and MRI) in 9 year-old children whose mothers used either metformin of insulin during pregnancy.

Detailed description: Gestational diabetes is usually managed with diet and insulin, if needed. However, oral metformin therapy has been also used to treat gestational diabetes and the short-term studies have shown that it is effective and also safe for the child. However, long-term studies of its effects are lacking.

Previously, several years ago, 217 pregnant women with gestational diabetes in Turku and 100 such women in Oulu, Finland, were randomised to either insulin or metformin therapy to treat gestational diabetes. In those studies, the metformin therapy proved to be safe in the short-term.

Now these children are 5-9 years old. In the present study these children (as well as their mothers) are investigated when the children are 9 years old. The aim is to study whether the metformin given during the pregnancy has any metabolic effects on the child at 9 years of age. To do this these families are contacted by mail and asked to participate into the study.

At 9 years of age, the following investigations will be made (after consent from the child and family): oral glucose tolerance test+insulin+c-peptide, plasma lipoproteins, adiponectin, PAI-1 (plasminogen activator inhibitor-1), IL-6 (interleukin-6), HS CRP (high-sensitivity C-reactive protein), p-metabolomics, DEXA, abdominal MRI, WISC IV (Wechsler intelligence scale for children IV)cognitive testing, BRIEF questionnaire, questionnaire about diet and health habits. The study subjects will also be clinically examined and measured and blood pressure will be taken.

All analyses are performed at the University hospital laboratory and radiology facilities using modern techniques. The amount of blood taken is limited and also radiation dose from DEXA is very small. The data are kept behind lock and key. Statistical analyses will be performed to study whether children exposed to metformin during pregnancy have any differences in their metabolism and well-being than those exposed to insulin. This study involves no new medical treatments to the study subjects.

Eligibility criteria: Inclusion Criteria:

* all children whose mothers used either metformin or insulin to treat gestational diabetes and were involved in the previous metformin study in Turku or Oulu, Finland

Exclusion Criteria:

* severe congenital malformations

Primary outcomes:
measure: Metabolic late effects
timeFrame: 9 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Turku
name: Harri J Niinikoski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tertti K, Ekblad U, Koskinen P, Vahlberg T, Ronnemaa T. Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Diabetes Obes Metab. 2013 Mar;15(3):246-51. doi: 10.1111/dom.12017. Epub 2012 Oct 24.
citation: Ijas H, Vaarasmaki M, Morin-Papunen L, Keravuo R, Ebeling T, Saarela T, Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study. BJOG. 2011 Jun;118(7):880-5. doi: 10.1111/j.1471-0528.2010.02763.x. Epub 2010 Nov 18.
citation: Tertti K, Ekblad U, Vahlberg T, Ronnemaa T. Comparison of metformin and insulin in the treatment of gestational diabetes: a retrospective, case-control study. Rev Diabet Stud. 2008 Summer;5(2):95-101. doi: 10.1900/RDS.2008.5.95. Epub 2008 Aug 10.
citation: Huhtala M, Nikkinen H, Paavilainen E, Niinikoski H, Vaarasmaki M, Loo BM, Ronnemaa T, Tertti K. Comparison of glucose metabolism and anthropometry in women with previous gestational diabetes treated with metformin vs. insulin: 9-year follow-up of two randomized trials. Acta Obstet Gynecol Scand. 2022 May;101(5):514-523. doi: 10.1111/aogs.14343. Epub 2022 Mar 11.
citation: Paavilainen E, Tertti K, Nikkinen H, Veijola R, Vaarasmaki M, Loo BM, Tossavainen P, Ronnemaa T, Niinikoski H. Metformin versus insulin therapy for gestational diabetes: Effects on offspring anthropometrics and metabolism at the age of 9 years: A follow-up study of two open-label, randomized controlled trials. Diabetes Obes Metab. 2022 Mar;24(3):402-410. doi: 10.1111/dom.14589. Epub 2021 Nov 24.