Gestational diabetes mellitus: Past present and future

Definition
GDM is defined as carbohydrate intolerance of variable severity that is first diagnosed during pregnancy, regardless of the need for insulin or persistence of the diabetic state after delivery. It is considered the most common metabolic complication of pregnancy.

Despite the decline in maternal and perinatal morbidity/ mortality in recent years, the care of pregnant women with GDM is still unclear, particularly regarding diagnosis.

Pathophysiology of GDM
The growth and development of the human conceptus take place within the metabolic milieu provided by the mother, where circulating maternal glucose, amino acids and lipids provide the building blocks for fetal development.

Abnormal maternal mixture of metabolites gain access to the developing fetus in-utero, modifying the phenotypic gene expression in newly forming cells, which in turn may lead to short and long-term effects in the offspring.
The fetal tissues most likely to be affected are neural cells, adipocytes, muscle cells and pancreatic -cells.

Pathophysiology of GDM

Pathophysiology of GDM contd

Screening and Diagnosis: GDM-Risk Assessment

Rationale

If diagnosed and treated early and appropriately, the risk of in-utero fetal death is no higher than for the general population of pregnant women. Among women with GDM, fetal morbidity is lower in those who achieve optimal glucose concentration than in those who do not.
Identification of those women early in pregnancy with previously undiagnosed type 2 diabetes. Maternal hyperglycaemia influences the future health of the child.

Screening and Diagnosis

Low risk GCT is unnecessary in patients meeting the following criteria: Belonging to an ethnic group that is not at risk of diabetes (ethnic groups at risk are Hispanics, Africans, South or South-East Asians) No history of diabetes in first degree relatives Age < 25 years Normal body weight before pregnancy No personal history of metabolic imbalance No history of adverse pregnancy outcome Average risk GCT should be performed in weeks 24-28 using one of the following two methods: Two stage testing: GCT with 50 g glucose, followed, if the results warrant, by an OGTT (75g or 100g, according to accepted criteria) One-stage testing: OGTT only (75g or 100g) High risk Testing should be performed as soon as feasible in women who meet the following criteria: Obese Family history of type 2 diabetes Personal history of GDM Glucose intolerance or glycosuria If findings are negative, testing should be repeated in weeks 24-28 of pregnancy or at the first signs of diabetes .

VALUES FOR DIAGNOSIS OF DIABETES AND OTHER CATEGORIES OF HYPERGLYCAEMIA

PARAMETER
FASTING

DM
7.0 mmol/L

IGT
<7.0 mmol/L

IFG
6.1 mmol/L and <7.0 mmol/L

GDM
7.0 mmol/L (126 mg/dl)

2HPP OGTT-75g FASTING 1-HR 2-HR OGTT-100g FASTING 1-HR 2-HR 3-HR

11.1 mmol/L

7.8 & <11.1 mmol/L

11.1 mmol/L (200 mg/dl)

5.3 mmol/L (95 mg/dl) 10.0 mmol/L (180 mg/dl) 8.6 mmol/L (155 mg/dl) 5.3 mmol/L (95 mg/dl) 10.0 mmol/L (180 mg/dl) 8.6 mmol/L (155 mg/dl) 7.8 mmol/L (140mg/dl)

Note: Diabetes can only be diagnosed in an asymptomatic individual when these diagnostic values are confirmed on another day. The classic symptoms of diabetes are polyuria, polydipsia and unexplained weight loss. Two or more of the venous plasma concentrations in OGTT must be met or exceeded for GDM. The test should be done in the morning after at least 3 days of unrestricted diet (>150g carbohydrate per day) and unlimited physical activity. The subject should remain seated and should not smoke throughout the test.

Reclassification
Normal Fasting glucose level <110(6.1) 75g OGTT <140 after 2h (7.8)

Glucose intolerance

110-25(6.1-6.9)

140-199 after 2h(7.8-11.1)

Diabetes

>126(7.0)

>200 after 2 h (11.1)

All values are in mg/dl.(mmol/L

Treatment
A. Glycaemic Targets (? Optimal levels)
FBG 95mg/dl (5.3mmo/l) 1-Hr Postprandial<140mg/dl (7.8) 2-Hr Postprandial <120mg/dl (6.7) Glucose and insulin levels in the fetus need to be measured. Glucose self monitoring better than laboratory monitoring. No place in management of GDM for urine glucose monitoring. During delivery
-plasma glucose 80-120mg/dl (4.4-6.7mm/L) -Whole blood glucose 70-110mg/dl (ie 3.9-6.1mm/L) ? Glycated Haemoglobin

Treatment contd
B. Diet Cornerstone of treatment Individualized depending
Personal needs Weight status (BMI) Level of daily physical activity ? Daily minimum caloric allowance (25kcals/kg body wt) _ Carbohydrate composition 35-55% _ Complex carbohydrates are recommended. Weight gain - 7kg in women who were overweight before pregnancy (BMI 29kg/m2) - up to 18kg in women who were underweight BMI 19.9kg/m2).

Treatment contd
C. Pharmacological Treatment If diet alone fails to maintain:
FBG < 5.5 mmo/L
1hr post meal < 8.0mmo/L

2hr post meal < 7.0mmo/L

Then insulin should be given

Long-term Effects and Post-natal Care

Reassess 2-6 wks after delivery.

GDM women are at a high risk of acquiring type 2 diabetes mellitus after delivery.

Those with negative findings should undergo repeat testing 1year later. After delivery should maintain regular physical activity and appropriate weight. Counseling before next pregnancy Recommend folic Acid to reduce possibility of fetal nervous system abnormalities (neural tube defects).

The future
Rationale

(The HAPO STUDY)

Need to develop uniform international measures for the detection of pregnancies at risk of poor outcome due to maternal hyperglycaemia.

Design and Time-line

This is a 5year investigator-initiated prospective, observational study. Recruited 25,000 pregnant women of different ethnic-racial backgrounds undergoing treatment in 16 leading obstetric centres in different geographic areas worldwide (10 Countries). Primary outcome indicators: - Caeserian delivery - Increased fetal size - Neonatal morbidity (hypoglycaemia) - Fetal hyperinsulinaemia

Findings will be published in 2005,

Conclusion
GDM definitely merits our attention as a distinct disease with significant prevalence by all standards of diagnostic criteria.

It is associated with a defined set of maternal and perinatal complications that adversely affect pregnancy outcome and also have long-term implications e.g. an increased risk of future diabetes for both mother and offspring.
However the following remain unresolved:- what degree of maternal hyperglycaemia is associated, with a measurable risk to the fetus? - At what level of maternal hyperglycaemia should we intervene to prevent the known maternal and perinatal morbidity and mortality? The HAPO study will hopefully answer these questions and more and establish an international consensus on the controversial issue of Diagnosis and management of GDM.