Gestational Diabetes Mellitus

Gestational diabetes mellitus: Gestational diabetes mellitus: Past present and futurePast present and future

DefinitionDefinition

GDM is defined as carbohydrate intolerance of GDM is defined as carbohydrate intolerance of variable severity that is first diagnosed during pregnancy, variable severity that is first diagnosed during pregnancy, regardless of the need for insulin or persistence of the diabetic regardless of the need for insulin or persistence of the diabetic state after delivery.state after delivery.

It is considered the most common metabolic It is considered the most common metabolic complication of pregnancy.complication of pregnancy.

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

Pathophysiology of GDMPathophysiology of GDM

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

Abnormal maternal mixture of metabolites gain Abnormal maternal mixture of metabolites gain access to the developing fetus in-utero, modifying the access to the developing fetus in-utero, modifying the phenotypic gene expression in newly forming cells, phenotypic gene expression in newly forming cells, which in turn may lead to short and long-term effects in which in turn may lead to short and long-term effects in the offspring.the offspring.

The fetal tissues most likely to be affected are The fetal tissues most likely to be affected are neural cells, adipocytes, muscle cells and pancreatic neural cells, adipocytes, muscle cells and pancreatic ββ--cells. cells.

Pathophysiology of GDM Pathophysiology of GDM

Pathophysiology of GDM Pathophysiology of GDM contdcontd

Screening and Diagnosis: GDM-Risk Screening and Diagnosis: GDM-Risk AssessmentAssessment

RationaleRationale

If diagnosed and treated early and appropriately, the risk If diagnosed and treated early and appropriately, the risk of in-utero fetal death is no higher than for the general of in-utero fetal death is no higher than for the general population of pregnant women.population of pregnant women.

Among women with GDM, fetal morbidity is lower in Among women with GDM, fetal morbidity is lower in those who achieve optimal glucose concentration than in those who achieve optimal glucose concentration than in those who do not.those who do not.

Identification of those women early in pregnancy with Identification of those women early in pregnancy with previously undiagnosed type 2 diabetes.previously undiagnosed type 2 diabetes.

Maternal hyperglycaemia influences the future health of Maternal hyperglycaemia influences the future health of the child.the child.

Screening and Diagnosis Screening and Diagnosis Low riskLow riskGCT is unnecessary in patients meeting the following criteria: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, Belonging to an ethnic group that is not at risk of diabetes (ethnic groups at risk are Hispanics,

Africans, South or South-East Asians)Africans, South or South-East Asians) No history of diabetes in first –degree relativesNo history of diabetes in first –degree relatives Age < 25 yearsAge < 25 years Normal body weight before pregnancyNormal body weight before pregnancy No personal history of metabolic imbalanceNo personal history of metabolic imbalance No history of adverse pregnancy outcomeNo history of adverse pregnancy outcomeAverage riskAverage riskGCT should be performed in weeks 24-28 using one of the following two methods: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 Two stage testing: GCT with 50 g glucose, followed, if the results warrant, by an OGTT (75g or

100g, according to accepted criteria)100g, according to accepted criteria) One-stage testing: OGTT only (75g or 100g)One-stage testing: OGTT only (75g or 100g)High riskHigh riskTesting should be performed as soon as feasible in women who meet the following criteriaTesting should be performed as soon as feasible in women who meet the following criteria:: ObeseObese Family history of type 2 diabetesFamily history of type 2 diabetes Personal history of GDMPersonal history of GDM Glucose intolerance or glycosuria Glucose intolerance or glycosuria If findings are negative, testing should be repeated in weeks 24-28 of pregnancy or at the first signs If findings are negative, testing should be repeated in weeks 24-28 of pregnancy or at the first signs

of diabetes .of diabetes .

PARAMETERPARAMETER DMDM IGTIGT IFGIFG GDMGDM

FASTINGFASTING ≥≥7.0 7.0 mmol/Lmmol/L

<7.0 mmol/L<7.0 mmol/L ≥≥6.1 6.1 mmol/Lmmol/L

and <7.0 and <7.0 mmol/Lmmol/L

≥≥7.0 mmol/L (126 mg/dl)7.0 mmol/L (126 mg/dl)

2HPP2HPP ≥≥11.1 11.1 mmol/Lmmol/L

7.8 & <11.1 7.8 & <11.1 mmol/Lmmol/L

11.1 mmol/L (200 mg/dl)11.1 mmol/L (200 mg/dl)

OGTT-75gOGTT-75g

FASTINGFASTING 5.3 mmol/L (95 mg/dl)5.3 mmol/L (95 mg/dl)

1-HR1-HR 10.0 mmol/L (180 mg/dl)10.0 mmol/L (180 mg/dl)


OGTT-100gOGTT-100g

FASTINGFASTING 5.3 mmol/L (95 mg/dl)5.3 mmol/L (95 mg/dl)



3-HR3-HR 7.8 mmol/L (140mg/dl)7.8 mmol/L (140mg/dl)

VALUES FOR DIAGNOSIS OF DIABETES AND OTHER CATEGORIES OF HYPERGLYCAEMIA

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.

ReclassificationReclassification

Fasting glucose levelFasting glucose level 75g OGTT 75g OGTT

Normal Normal <110(6.1)<110(6.1) <140 after 2h (7.8) <140 after 2h (7.8)

Glucose intolerance 110-25(6.1-6.9)Glucose intolerance 110-25(6.1-6.9) 140-199 after 2h(7.8- 140-199 after 2h(7.8-11.1)11.1)

Diabetes Diabetes >126(7.0)>126(7.0) >200 after 2 h (11.1) >200 after 2 h (11.1)

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

Treatment Treatment A.A. Glycaemic Targets (Glycaemic Targets (? Optimal levels)? Optimal levels)

FBG FBG ≤ 95mg/dl (5.3mmo/l)≤ 95mg/dl (5.3mmo/l)

1-Hr Postprandial<140mg/dl (7.8)1-Hr Postprandial<140mg/dl (7.8)

2-Hr Postprandial <120mg/dl (6.7)2-Hr Postprandial <120mg/dl (6.7)

Glucose and insulin levels in the fetus need to be measured.Glucose and insulin levels in the fetus need to be measured.

Glucose self monitoring better than laboratory monitoring.Glucose self monitoring better than laboratory monitoring.

No place in management of GDM for urine glucose monitoring.No place in management of GDM for urine glucose monitoring.

During delivery During delivery -plasma glucose 80-120mg/dl (4.4-6.7mm/L)-plasma glucose 80-120mg/dl (4.4-6.7mm/L)-Whole blood glucose 70-110mg/dl (ie 3.9-6.1mm/L)-Whole blood glucose 70-110mg/dl (ie 3.9-6.1mm/L)? Glycated Haemoglobin ? Glycated Haemoglobin

Treatment contdTreatment contd

B. DietB. Diet Cornerstone of treatment Cornerstone of treatment Individualized depending Individualized depending

Personal needsPersonal needs Weight status (BMI)Weight status (BMI) Level of daily physical activityLevel of daily physical activity? Daily minimum caloric allowance (25kcals/kg body wt)? Daily minimum caloric allowance (25kcals/kg body wt)_ Carbohydrate composition 35-55%_ Carbohydrate composition 35-55%_ Complex carbohydrates are recommended._ Complex carbohydrates are recommended.Weight gain Weight gain

- 7kg in women who were overweight before - 7kg in women who were overweight before pregnancy (BMI pregnancy (BMI ≥ 29kg/m≥ 29kg/m22))- up to 18kg in women who were underweight BMI - up to 18kg in women who were underweight BMI ≤19.9kg/m≤19.9kg/m22).).

Treatment contdTreatment contd

C. C. Pharmacological TreatmentPharmacological Treatment If diet alone fails to maintain:If diet alone fails to maintain:

FBG < 5.5 mmo/LFBG < 5.5 mmo/L

1hr post meal < 8.0mmo/L1hr post meal < 8.0mmo/L

2hr post meal < 7.0mmo/L2hr post meal < 7.0mmo/L

Then insulin should be givenThen insulin should be given

Long-term Effects and Long-term Effects and Post-natal CarePost-natal Care GDM women are at a high risk of acquiring type 2 GDM women are at a high risk of acquiring type 2

diabetes mellitus after delivery.diabetes mellitus after delivery.

Reassess 2-6 wks after delivery.Reassess 2-6 wks after delivery.

Those with negative findings should undergo repeat Those with negative findings should undergo repeat testing 1year later.testing 1year later.

After delivery should maintain regular physical activity After delivery should maintain regular physical activity and appropriate weight.and appropriate weight.

Counseling before next pregnancy Counseling before next pregnancy

Recommend folic Acid to reduce possibility of fetal Recommend folic Acid to reduce possibility of fetal nervous system abnormalities (neural tube defects). nervous system abnormalities (neural tube defects).

The futureThe future (The HAPO STUDY)(The HAPO STUDY)

RationaleRationale

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

Design and Time-lineDesign and Time-line

This is a 5year investigator-initiated prospective, observational study.This is a 5year investigator-initiated prospective, observational study.

Recruited 25,000 pregnant women of different ethnic-racial backgrounds Recruited 25,000 pregnant women of different ethnic-racial backgrounds undergoing treatment in 16 leading obstetric centres in different geographic undergoing treatment in 16 leading obstetric centres in different geographic areas worldwide (10 Countries).areas worldwide (10 Countries).

Primary outcome indicators:Primary outcome indicators:- Caeserian delivery- Caeserian delivery- Increased fetal size- Increased fetal size- Neonatal morbidity (hypoglycaemia)- Neonatal morbidity (hypoglycaemia)- Fetal hyperinsulinaemia- Fetal hyperinsulinaemia

--Findings will be published in 2005,Findings will be published in 2005,

ConclusionConclusionGDM definitely merits our attention as a distinct disease GDM definitely merits our attention as a distinct disease

with significant prevalence by all standards of diagnostic criteria.with significant prevalence by all standards of diagnostic criteria.

It is associated with a defined set of maternal and perinatal It is associated with a defined set of maternal and perinatal complications that adversely affect pregnancy outcome and also complications that adversely affect pregnancy outcome and also have long-term implications e.g. an increased risk of future diabetes have long-term implications e.g. an increased risk of future diabetes for both mother and offspring.for both mother and offspring.

However the following remain unresolvedHowever the following remain unresolved:-:-- what degree of maternal hyperglycaemia is - what degree of maternal hyperglycaemia is

associated, with a measurable risk to the fetus?associated, with a measurable risk to the fetus?- At what level of maternal hyperglycaemia should - At what level of maternal hyperglycaemia should

we intervene to prevent the known maternal and perinatal morbidity we intervene to prevent the known maternal and perinatal morbidity and mortality?and mortality?

The HAPO study will hopefully answer these questions and The HAPO study will hopefully answer these questions and more and establish an international consensus on the controversial more and establish an international consensus on the controversial issue of Diagnosis and management of GDM. issue of Diagnosis and management of GDM.

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Gestational Diabetes Mellitus