Short summary

Women with previous Gestational Diabetes Mellitus (GDM) are at high risk of developing subsequent overt diabetes. Thus, it is important to identify potentially modifiable factors at an early stage. GDM subjects in this cohort were examined thoroughly in the post-partum period and 7-8 years later including anthropometrics, glucose metabolism during oral glucose tolerance test (OGTT) and Glutamatdecarboxylase (GAD) autoantibodies. In addition, self-reported lifestyle factors and indicators of Polycystic Ovary Syndrome (PCOS) were assessed at follow-up.

The overall aim of the study is to determine predictive factors for development of Diabetes Mellitus/Pre-Diabetes (pre-DM) in women with previous GDM.

Rationale

It is well established that women with previous GDM are characterized by several metabolic abnormalities, such as insulin resistance and beta-cell dysfunction and increased risk of later Diabetes Mellitus (DM). Furthermore, GDM is a heterogeneous condition covering both women with a strong genetic disposition to type 2 DM, women in the early stages of autoimmune DM and rare cases of monogenetic DM. These latent disorders of glucose metabolism are damasked by the metabolic stress of pregnancy. 

Our current population is unique as clinical, metabolic and autoimmune markers were determined prospectively a few months after GDM pregnancy and at follow-up. Hopefully, the results will enable us to target preventive actions in women with previous GDM and improve our understanding of pathophysiologic mechanisms in pre-diabetic conditions. 

The aims of this project are

1. To study the prevalence of DM (type 2 DM and autoimmune DM) and pre-DM in women with previous GDM 7-8 years after pregnancy.
2. To study potential post-partum predictive factors for developing later DM/pre-DM:
• Demography at the time of GDM pregnancy: age, blood pressure, Body Mass Index (BMI)
• Metabolic factors post-partum: indices of insulin sensitivity and beta-cell function, measurements of cholesterol and lipoprotein
• GAD-autoantibodies post-partum.
3. To study phenotypic characteristics of GAD-antibody-positive women compared to GAD-antibody-negative women at the time of post-partum testing
4. To study lifestyle factors 7-8 years after GDM pregnancy in relation to current glucose tolerance  
5. To study PCOS as an additional risk factor for developing DM/pre-DM

Description of the cohort

During 1997-2010 women with GDM delivering at Odense University Hospital in Southern Denmark were routinely offered testing 3-months post-partum with 2-h OGTT, clinical examination and counselling at the Department of Endocrinology, Odense University Hospital.

Follow-up: During 2011-2016 the cohort of women with previous GDM and a control group are invited to a long-term follow-up with OGTT, venous blood samples including glucose, insulin, cholesterol and lipoprotein measurements, GAD-auto-antibodies, clinical examination and questionnaires addressing lifestyle factors and indices of PCOS.

Data and biological material

Women with previous GDM:

Data from hospital journals at the time of GDM pregnancy:

Parity, ethnicity, pre-gestational weight and height, family history of DM, gestational age (GA) at diagnostic 2-h 75 g OGTT, GDM treatment, OGTT results during pregnancy (fasting and 2-h capillary blood glucose), offspring birth weight and length, GA at delivery.

Post-partum examinations:

Blood pressure, weight (incomplete data set), 2-h 75 g OGTT with measurements of glucose, C-peptide  and insulin at 0, 30 and 120 minutes, fasting total cholesterol, HDL, LDL and triglycerides and GAD- autoantibodies.

Controls without previous GDM:

Data from hospital journals at the time of GDM pregnancy:

Parity, ethnicity, pre-gestational weight and height, family history of DM, offspring birth weight and length, GA at delivery. These women are identified from the national birth registry and matched on age, parity, BMI and year of pregnancy.

The above-mentioned data are extracted from hospital journals and laboratory charts. The women (both GDM subjects and controls) have given informed consent, that these data can be studied.

Women with previous GDM and controls:

Data collection 7-8 years after GDM pregnancy:

1. Anthropometrics: weight, height, waist circumference, blood pressure and length
2. Prospective analyses: venous samples: p-glucose, C-peptide and insulin at 0, 30 and 120 minutes during a 2-h 75 g OGTT, fasting total cholesterol, HDL, LDL triglycerides, GAD- autoantibodies, Hba1c, TSH, kidney and liver parameters. Urine samples: U-albumin/creatinine ratio.
3. Biobank
4. Questionnaires: Information about lifestyle and health status (medical history, family history of diabetes, history of PCOS, diet, exercise, ethnicity, socioeconomic status).

Collaborating researchers and departments

Department of Endocrinology, Odense University Hospital

• Consultant and "Associate Professor Dorte Møller Jensen, MD, PhD
• Project Manager Trine Præstekjær Lundberg, MD
• Project Manager and Medical student Ida Siobhan Smietana
• Lena Sønder Snogdal, MD, PhD
• Consultant and Professor Marianne Andersen, DMSc
• Professor Kurt Højlund Consultant, DMSc
• Consultant Dorte Glintborg, PhD

Publications associated with the project

Glutamic acid decarboxylase autoantibody-positivity post-partum is associated with impaired beta-cell function in women with gestational diabetes mellitus. / Lundberg TP, Hojlund K, Snogdal LS, Jensen DM. Diabet Med. 2015 Feb;32(2):198-205.