M.G.S.D. The Gestational Diabetes Study in the Mediterranean Region Protocol C. Savona-Ventura Research Management Committee – M.G.S.D.

Prevalence of DM & IGT in the Mediterranean Region The Mediterranean area represents a unique regional example of the interplay of varying ethnic variations and socio-economic differences. Prevalence estimates of diabetes mellitus (DM) - European Region. Diabetes Atlas, International Diabetes Federation, Belgium, 2nd edition, 2003.

The relative high prevalence of Type 2 DM in populations living in the Mediterranean region should be reflected as similar elevated prevalence of Gestational DM, since the pregnant state brings out to the front any underlying insulin resistance. Literature-defined risk factor criteria for GDM may be different in the Mediterranean population. Mediterranean diet may influence the obstetric outcomes of an altered carbohydrate profile.

Aims of the Study Primary objectives: –to identify the biological profile and risk factors of Mediterranean pregnant women with GDM. –to relate obstetric outcome to carbohydrate metabolic profile. –to assess the nutritional dietary practices among pregnant Mediterranean women and the possible influence of these to the development of GDM. Secondary objectives: –to assess the sociological impact of the diagnostic criteria being currently proposed.

Study plan Prospective, non-interventional, multicenter study –It did not in any way directly intervene in obstetric or medical management protocols, and each centre managed its patients using its own established protocols. Any medically relevant abnormal results were communicated to the patient. Exclusion criteria –Women with a known history of diabetes [Type 1, Type 2 or MODY] in the non- pregnant state were excluded from the study; but a history of previous GDM was not an exclusion criterion. Ethical approval –Obtained from relevant local bodies in all the participating centres. Study population –The number of study participants from each centre was established at women. –Sample size for a prevalence study with 95% confidence level with total births = 3500  Assume 10% prevalence  sample size = ~100  error margin = 5.8%

Study design Main evaluation criteria: –The diagnosis of GDM is made using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. The test done in the morning after an overnight fast of between 8 and 14 hours and after at least 3 days of unrestricted diet (>=150 g carbohydrate per day), and unlimited physical activity. The subject remained seated throughout the test. –Test done at weeks of gestation Diagnostic criteria: 75-gram oGTT subgroup criteria NormalNormal highModerate GDM Severe GDM Fasting plasma glucose < 4.5 mmol/l mmol/l mmol/l> 7.0 mmol/l 1-hour post load plasma glucose < 9.4 mmol/l mmol/l mmol/l> 11.0 mmol/l 2-hour post load plasma glucose < 7.7 mmol/l mmol/l mmol/l> 11.0 mmol/l

Methodology V1 – Inclusion visit  weeks of pregnancy [preferably as close to 28 weeks as possible]. –The women were assessed with the aim of screening for known high risk factors such as body weight, height and BMI; age; history of recurrent miscarriage, unexplained past stillbirth and macrosomia; irregular menses and need for artificial reproductive technology; and hypertensive disease including pre-existing, gestational or pre- eclampsia. –A dietary and nutritional assessment of each patient was also carried out at this visit. –The women then underwent a 75-gram oral glucose tolerance test that included a fasting insulin, HbA1c and other haematological parameters. V2 – Follow-up visit  At Delivery –The data relevant to the obstetric and neonatal outcome was then collected at the time of delivery. V3 – Follow-up visit  6 weeks postpartum for women diagnosed as GDM –Women shown to have an abnormal oGTT during pregnancy [ADA criteria] were subsequently retested six weeks later for reclassification of their carbohydrate metabolism status.

Cryobox Biopouch with cryobox and temperature indicator Polyestyrene box with biopouch Box filled with 6 lbs of Dry Carbo Ice Insulin assays were centralised in one laboratory [Biochemistry Department, Mater Dei University Hospital, Malta]. Transport of the samples was carried out under strict conditions requiring the serum to be frozen and maintained at C at all times. Frozen serum samples sent by Marken ® with continuous temperature monitoring of the package during transport

Data collection The individual centres entered the data maintaining patient anonymity using a dedicated web-based secure electronic data-entry system.

Country participants TOTAL STUDY POPULATION: 1210 women