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.

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

30.00%

DM IGT

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 75-200

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 24-32 weeks of gestation

• Diagnostic criteria:

75-gram oGTT

subgroup criteria

Normal Normal high Moderate GDM

Severe GDM

Fasting plasma glucose < 4.5 mmol/l 4.6-5.2 mmol/l 5.3-6.9 mmol/l > 7.0 mmol/l

1-hour post load plasma glucose < 9.4 mmol/l 9.5-9.9 mmol/l 10.0-10.9 mmol/l > 11.0 mmol/l

2-hour post load plasma glucose < 7.7 mmol/l 7.8-8.5 mmol/l 8.6-10.9 mmol/l > 11.0 mmol/l

Methodology• V1 – Inclusion visit 24-32 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 -200C 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

200

82

177

93136

108 112

92

126

84

TOTAL STUDY POPULATION: 1210 women