(JULY�2015�‒�OCTOBER�2015)

SAFES 2014-16

(JULY�2015�‒�OCTOBER�2015)

SAFES 2014-16

Module I: Introduction to Diabetes in Pregnancy

Disclaimer

Public Health Foundation of India (PHFI) and Dr. Mohan’s Diabetes Education

Academy (DMDEA) do not recommend or provide individualized medical

diagnosis, treatment or advice, nor do they recommend specific therapies

or prescribe medication for anyone using or consulting this publication. The

information contained in this publication is intended for general educational

and informational purposes only.

Medical information changes rapidly. Therefore, PHFI and DMDEA assume no

responsibility for how readers use the information contained in this publication

and hence assume no legal liability or responsibility arising out of use of this

information.

Contents included in this module are solely provided by designated experts and

represents their viewpoints entirely.

© Copyright 2015 Public Health Foundation of India, New Delhi & Dr. Mohan’s

Diabetes Education Academy, Chennai. All rights reserved.

This training material (including print material, CDs, Modules and presentations)

is the exclusive intellectual property right of PHFI and DMDEA. No part of this

training material may be reproduced, stored in a retrieval system, or transmitted

in any form or by any means, electronic, mechanical, photocopying, recording,

or otherwise, without the prior written permission of PHFI and DMDEA.

SAFES 2014-16

Layout, designed & printed by Fluorescence Communications Pvt. Ltd.UG 31-32, Suneja Tower-I, District Center, Janakpuri, New Delhi - 110058+911140595155 | www.fcommunications.in

2

Module I: Introduction to Diabetes in Pregnancy

Disclaimer

Public Health Foundation of India (PHFI) and Dr. Mohan’s Diabetes Education

Academy (DMDEA) do not recommend or provide individualized medical

diagnosis, treatment or advice, nor do they recommend specific therapies

or prescribe medication for anyone using or consulting this publication. The

information contained in this publication is intended for general educational

and informational purposes only.

Medical information changes rapidly. Therefore, PHFI and DMDEA assume no

responsibility for how readers use the information contained in this publication

and hence assume no legal liability or responsibility arising out of use of this

information.

Contents included in this module are solely provided by designated experts and

represents their viewpoints entirely.

© Copyright 2015 Public Health Foundation of India, New Delhi & Dr. Mohan’s

Diabetes Education Academy, Chennai. All rights reserved.

This training material (including print material, CDs, Modules and presentations)

is the exclusive intellectual property right of PHFI and DMDEA. No part of this

training material may be reproduced, stored in a retrieval system, or transmitted

in any form or by any means, electronic, mechanical, photocopying, recording,

or otherwise, without the prior written permission of PHFI and DMDEA.

SAFES 2014-16

Layout, designed & printed by Fluorescence Communications Pvt. Ltd.UG 31-32, Suneja Tower-I, District Center, Janakpuri, New Delhi - 110058+911140595155 | www.fcommunications.in

2

Introduction to Certificate Course in Gestational Diabetes Mellitus-Cycle III

Learning Objectives

Introduction to Diabetes in Pregnancy

Appendix

Presentations

Primer to Module II

4

6

7

12

15

36

Contents

4

Introduction to Certificate Course in Gestational Diabetes Mellitus (CCGDM) Cycle III

Introduction

On behalf of Public Health Foundation of India and Dr. Mohan’s Diabetes Education Academy, we wish

you a warm welcome to the Certificate Course in Gestational Diabetes Mellitus (CCGDM)-Cycle III. We

congratulate you on having been selected to undergo this course and thank you for agreeing to spare

your valuable time to ensure the success of this course.

The CCGDM is designed to equip general practitioners, physicians and obstetricians / gynecologists

with the information and tools needed to manage Gestational Diabetes Mellitus (GDM) and pre-existing

diabetes in pregnancy in a clinical setting. The Course will be delivered on a Modular basis. There are

four Modules, each of which will be delivered on a fixed Sunday every month.

The Modules consist of:

Pre-test

The day’s discussions start with listing of the learning objectives. You can help in making the session

more interactive by presenting interesting cases you have seen in your practice.

This is then followed by the pre-test. This consists of ten multiple choice questions (MCQs) based on

the topic to be covered during the particular session. This is designed to assess the trainees’ baseline

knowledge. The same set of MCQs will be administered as the post-test at the end of the session,

following which your facilitator will discuss the answers with you.

Primer to Next Module

Post test

Take home messages

Group work activity

Video

Case exercise

Case studies

Teaching slides

Learning objectives

Introduction to Certificate Course in Gestational Diabetes Mellitus-Cycle III

Learning Objectives

Introduction to Diabetes in Pregnancy

Appendix

Presentations

Primer to Module II

4

6

7

12

15

36

Contents

4

Introduction to Certificate Course in Gestational Diabetes Mellitus (CCGDM) Cycle III

Introduction

On behalf of Public Health Foundation of India and Dr. Mohan’s Diabetes Education Academy, we wish

you a warm welcome to the Certificate Course in Gestational Diabetes Mellitus (CCGDM)-Cycle III. We

congratulate you on having been selected to undergo this course and thank you for agreeing to spare

your valuable time to ensure the success of this course.

The CCGDM is designed to equip general practitioners, physicians and obstetricians / gynecologists

with the information and tools needed to manage Gestational Diabetes Mellitus (GDM) and pre-existing

diabetes in pregnancy in a clinical setting. The Course will be delivered on a Modular basis. There are

four Modules, each of which will be delivered on a fixed Sunday every month.

The Modules consist of:

Pre-test

The day’s discussions start with listing of the learning objectives. You can help in making the session

more interactive by presenting interesting cases you have seen in your practice.

This is then followed by the pre-test. This consists of ten multiple choice questions (MCQs) based on

the topic to be covered during the particular session. This is designed to assess the trainees’ baseline

knowledge. The same set of MCQs will be administered as the post-test at the end of the session,

following which your facilitator will discuss the answers with you.

Primer to Next Module

Post test

Take home messages

Group work activity

Video

Case exercise

Case studies

Teaching slides

Learning objectives

5

The teaching slides have been designed to be as interactive as possible. A number of case studies

have also been interspersed among the slides. Please remember that there may not be any “right” or

“wrong” answer for many of these; they are only meant to provoke thought and discussion.

In addition to the pre-test and post-test, you are also expected to submit a case exercise at the

beginning of module III and to make the course as interactive a possible, one group work activity have

been scheduled in module IV. Please distribute the handouts among the participants, get the activity

done and facilitate the discussion at the end of the activity.

There will also be an Exit Exam in the form of MCQs at the completion of Module IV, a minimum of

50 % marks is required to pass, which will be one of the criteria for award of the certificate. Further

details will be communicated to you closer to the date of the Exam.

The Curriculum for the CCGDM has been designed with inputs from eminent Endocrinologists,

Diabetologists and Obstetricians / Gynecologists who have agreed to act as the National Expert Panel

for this Course. We are thankful to them for sharing their valuable time and invaluable expertise in

designing this course. Even though all efforts have been made to ensure that the information provided

is accurate and up to date, you may occasionally come across instances where this is not so. We request

you to point these errors and omissions to us so that we can rectify them in time for the Cycle IV.

Further Reading

1. Seshiah V, Das AK, Balaji V, Joshi SR, Parikh MN, Gupta S for the Diabetes in Pregnancy Study Group (DIPSI).

Gestational diabetes mellitus- Guidelines. J Assoc Physicians India 2006;54:622-628.

2. Banerjee S, Seshiah V, Zargar AH. Diabetes in Pregnancy- ECAB. New Delhi, Elsevier India, 2012.

3. Hod M, Jovanovic L, Di Renzo GC, De Leiva A, Langer O (Eds.). Textbook of Diabetes and Pregnancy, 2nd

Edition. London, Informa Healthcare, 2008.

4. Metzger BE, Buchanan TA, Coustan DR, De Leiva A, Bunger DB, Hadden DR et al. Summary and recommendations

of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 2007;30

(Suppl.2):s251-s260.

5. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International

Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification

of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-689.

that you will find this Course

Interesting, Enjoyable

& Informative !

We are sure

Module I: Introduction to Diabetes in Pregnancy

6

Learning Objectives• Learn about the evolution of the concept of

diabetes in pregnancy

• Review the metabolic alterations occurring

in pregnancy and how these can lead to

diabetes

• Define GDM and discuss its epidemiology

• Learn about the consequences of GDM to

the mother and fetus

• Understand the great public health

importance of GDM

Certificate Course in Gestational Diabetes Mellitus

5

The teaching slides have been designed to be as interactive as possible. A number of case studies

have also been interspersed among the slides. Please remember that there may not be any “right” or

“wrong” answer for many of these; they are only meant to provoke thought and discussion.

In addition to the pre-test and post-test, you are also expected to submit a case exercise at the

beginning of module III and to make the course as interactive a possible, one group work activity have

been scheduled in module IV. Please distribute the handouts among the participants, get the activity

done and facilitate the discussion at the end of the activity.

There will also be an Exit Exam in the form of MCQs at the completion of Module IV, a minimum of

50 % marks is required to pass, which will be one of the criteria for award of the certificate. Further

details will be communicated to you closer to the date of the Exam.

The Curriculum for the CCGDM has been designed with inputs from eminent Endocrinologists,

Diabetologists and Obstetricians / Gynecologists who have agreed to act as the National Expert Panel

for this Course. We are thankful to them for sharing their valuable time and invaluable expertise in

designing this course. Even though all efforts have been made to ensure that the information provided

is accurate and up to date, you may occasionally come across instances where this is not so. We request

you to point these errors and omissions to us so that we can rectify them in time for the Cycle IV.

Further Reading

1. Seshiah V, Das AK, Balaji V, Joshi SR, Parikh MN, Gupta S for the Diabetes in Pregnancy Study Group (DIPSI).

Gestational diabetes mellitus- Guidelines. J Assoc Physicians India 2006;54:622-628.

2. Banerjee S, Seshiah V, Zargar AH. Diabetes in Pregnancy- ECAB. New Delhi, Elsevier India, 2012.

3. Hod M, Jovanovic L, Di Renzo GC, De Leiva A, Langer O (Eds.). Textbook of Diabetes and Pregnancy, 2nd

Edition. London, Informa Healthcare, 2008.

4. Metzger BE, Buchanan TA, Coustan DR, De Leiva A, Bunger DB, Hadden DR et al. Summary and recommendations

of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 2007;30

(Suppl.2):s251-s260.

5. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International

Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification

of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-689.

that you will find this Course

Interesting, Enjoyable

& Informative !

We are sure

Module I: Introduction to Diabetes in Pregnancy

6

Learning Objectives• Learn about the evolution of the concept of

diabetes in pregnancy

• Review the metabolic alterations occurring

in pregnancy and how these can lead to

diabetes

• Define GDM and discuss its epidemiology

• Learn about the consequences of GDM to

the mother and fetus

• Understand the great public health

importance of GDM

Certificate Course in Gestational Diabetes Mellitus

Module I: Introduction to Diabetes in Pregnancy

7

Introduction to Diabetes in Pregnancy

History of Diabetes in Pregnancy

Until the middle of the 19th century, diabetes was thought to be incompatible with successful pregnancy.

Blott, writing in Paris in 1856, concluded that “true diabetes was inconsistent with conception”. This

statement was probably linked to the short life expectancy of women with type 1 diabetes in the

days before insulin was discovered, meaning that their chances of surviving long enough to reach

reproductive age were negligible.

Even in those women who managed to conceive, death from uncontrolled diabetes during or soon

after pregnancy was exceedingly common. The dire outlook for women with pre-existing diabetes

did not change until a few years after the discovery of insulin, when the subspeciality of diabetes in

pregnancy was created following the efforts of Priscilla White and other pioneers.

The concept of “Gestational Diabetes” that is, diabetes occurring on account of the pregnancy itself,

dates back to the middle of the 19th century. In 1824 a German physician, Bennewitz, described a single

case in whom diabetes developed following conception, only to disappear after delivery (her baby

weighed 12 pounds at birth and was said to be “robust and healthy”).

The term “Gestational Diabetes” was first used by O’Sullivan in 1961, following the lead of Hoet from

Belgium who used the term “Metagestational Diabetes”.

Definition of Gestational Diabetes Mellitus (GDM)

Gestational diabetes is defined as “glucose intolerance of varying severity with onset or first recognition

during pregnancy”. This definition does not discount the possibility that diabetes could have existed

prior to the pregnancy. Therefore we can have different categories of women clubbed together under

this definition:

Normal glucose tolerance prior to pregnancy which becomes abnormal with pregnancy and returns to normal following delivery (“True GDM”)

Mild glucose intolerance (“pre-diabetes”) before pregnancy which worsens during pregnancy

Previously undiagnosed type 2 diabetes

Previously undiagnosed type 1 diabetes (rare)

Previously undiagnosed MODY or secondary forms of diabetes (rare)

As will be seen from the subsequent discussions, it is important to differentiate gestational diabetes from pre-existing diabetes in pregnancy. The classification of diabetes and the diagnostic criteria in non-pregnant individuals are described in the Appendix.

8

Pathogenesis of Diabetes in Pregnancy

Metabolic Alterations Occurring During Pregnancy

During pregnancy, maternal intermediary metabolism undergoes major changes, most of which are

designed to provide a continuous supply of energy and nutrients to the growing fetus while also

meeting the nutritional requirements of the mother.

From the metabolic standpoint, pregnancy can be divided into two distinct halves:

During the first half of pregnancy, there occur changes that promote storage of energy and nutrients. At this point, there is increased appetite combined with normal or increased insulin sensitivity. This promotes storage of energy in the form of fat. These accumulated energy reserves can then be used during the second half of pregnancy to meet the demands of the rapidly growing fetus.

In the second half of pregnancy, there develops a state of insulin resistance in the mother, facilitating preferential supply of glucose to the growing fetus. Insulin resistance reduces the uptake of glucose by maternal tissues such as white adipose tissue and skeletal muscle, and diverts glucose to the fetus. The mother’s energy requirements are met using alternate fuels such as free fatty acids and ketone bodies. Increased uptake of glucose by the fetus leads to low maternal fasting plasma glucose levels. Human Placental Lactogen (HPL) secreted by the placenta is the main driver of insulin resistance in pregnancy. Other hormones implicated include cortisol, prolactin and progesterone.

Intermediary metabolism in late pregnancy has been described as an exaggeration of the normal

swings between fed-state anabolism and fasting catabolism that occur in nonpregnant individuals.

During feeding, glucose and insulin concentrations increase rapidly as a result of the marked insulin

resistance and compensatory hyperinsulinemia. Following a period of no calorie intake, blood glucose

levels fall much more rapidly than in nonpregnant individuals and insulin release is suppressed. This

leads to accelerated lipolysis and ketone body formation (“accelerated starvation”)

Fig. 1.1: Schematic representation of maternal metabolic changes during gestation. Anabolism during feeding and catabolism during fasting are

exaggerated in a progressive fashion, reflecting the combined effects of placental hormones and nutrient use by the fetus. Ref: Buchanan TA, Coustan

DR. Diabetes mellitus. In: Burrows GN, Ferris TF, eds. Medical complications during pregnancy, 4th ed. Philadelphia: WB Saunders,1994:29–61.

Figure 1.1

Certificate Course in Gestational Diabetes Mellitus

Module I: Introduction to Diabetes in Pregnancy

7

Introduction to Diabetes in Pregnancy

History of Diabetes in Pregnancy

Until the middle of the 19th century, diabetes was thought to be incompatible with successful pregnancy.

Blott, writing in Paris in 1856, concluded that “true diabetes was inconsistent with conception”. This

statement was probably linked to the short life expectancy of women with type 1 diabetes in the

days before insulin was discovered, meaning that their chances of surviving long enough to reach

reproductive age were negligible.

Even in those women who managed to conceive, death from uncontrolled diabetes during or soon

after pregnancy was exceedingly common. The dire outlook for women with pre-existing diabetes

did not change until a few years after the discovery of insulin, when the subspeciality of diabetes in

pregnancy was created following the efforts of Priscilla White and other pioneers.

The concept of “Gestational Diabetes” that is, diabetes occurring on account of the pregnancy itself,

dates back to the middle of the 19th century. In 1824 a German physician, Bennewitz, described a single

case in whom diabetes developed following conception, only to disappear after delivery (her baby

weighed 12 pounds at birth and was said to be “robust and healthy”).

The term “Gestational Diabetes” was first used by O’Sullivan in 1961, following the lead of Hoet from

Belgium who used the term “Metagestational Diabetes”.

Definition of Gestational Diabetes Mellitus (GDM)

Gestational diabetes is defined as “glucose intolerance of varying severity with onset or first recognition

during pregnancy”. This definition does not discount the possibility that diabetes could have existed

prior to the pregnancy. Therefore we can have different categories of women clubbed together under

this definition:

Normal glucose tolerance prior to pregnancy which becomes abnormal with pregnancy and returns to normal following delivery (“True GDM”)

Mild glucose intolerance (“pre-diabetes”) before pregnancy which worsens during pregnancy

Previously undiagnosed type 2 diabetes

Previously undiagnosed type 1 diabetes (rare)

Previously undiagnosed MODY or secondary forms of diabetes (rare)

As will be seen from the subsequent discussions, it is important to differentiate gestational diabetes from pre-existing diabetes in pregnancy. The classification of diabetes and the diagnostic criteria in non-pregnant individuals are described in the Appendix.

8

Pathogenesis of Diabetes in Pregnancy

Metabolic Alterations Occurring During Pregnancy

During pregnancy, maternal intermediary metabolism undergoes major changes, most of which are

designed to provide a continuous supply of energy and nutrients to the growing fetus while also

meeting the nutritional requirements of the mother.

From the metabolic standpoint, pregnancy can be divided into two distinct halves:

During the first half of pregnancy, there occur changes that promote storage of energy and nutrients. At this point, there is increased appetite combined with normal or increased insulin sensitivity. This promotes storage of energy in the form of fat. These accumulated energy reserves can then be used during the second half of pregnancy to meet the demands of the rapidly growing fetus.

In the second half of pregnancy, there develops a state of insulin resistance in the mother, facilitating preferential supply of glucose to the growing fetus. Insulin resistance reduces the uptake of glucose by maternal tissues such as white adipose tissue and skeletal muscle, and diverts glucose to the fetus. The mother’s energy requirements are met using alternate fuels such as free fatty acids and ketone bodies. Increased uptake of glucose by the fetus leads to low maternal fasting plasma glucose levels. Human Placental Lactogen (HPL) secreted by the placenta is the main driver of insulin resistance in pregnancy. Other hormones implicated include cortisol, prolactin and progesterone.

Intermediary metabolism in late pregnancy has been described as an exaggeration of the normal

swings between fed-state anabolism and fasting catabolism that occur in nonpregnant individuals.

During feeding, glucose and insulin concentrations increase rapidly as a result of the marked insulin

resistance and compensatory hyperinsulinemia. Following a period of no calorie intake, blood glucose

levels fall much more rapidly than in nonpregnant individuals and insulin release is suppressed. This

leads to accelerated lipolysis and ketone body formation (“accelerated starvation”)

Fig. 1.1: Schematic representation of maternal metabolic changes during gestation. Anabolism during feeding and catabolism during fasting are

exaggerated in a progressive fashion, reflecting the combined effects of placental hormones and nutrient use by the fetus. Ref: Buchanan TA, Coustan

DR. Diabetes mellitus. In: Burrows GN, Ferris TF, eds. Medical complications during pregnancy, 4th ed. Philadelphia: WB Saunders,1994:29–61.

Figure 1.1

Certificate Course in Gestational Diabetes Mellitus

Module I: Introduction to Diabetes in Pregnancy

9

Pathogenesis of GDM

GDM develops when the maternal pancreatic beta cell is unable to compensate for the insulin resistance

of late pregnancy by increasing its output of insulin. While the exact nature of the beta cell defect

remains unknown, the following factors may play a role.

Genetic factors

Chronic insulin resistance preceding pregnancy (which would have already worn out the beta cell)

Subclinical inflammation

Since insulin resistance develops only during the second trimester of pregnancy, GDM is very

unlikely to develop before this time. Diabetes diagnosed during the first trimester usually

indicates pre-existing type 2 diabetes rather than GDM.

Risk Factors for GDM

The following have conventionally been considered to be risk factors for GDM:

Obesity

Metabolic syndrome/ diabetes in first degree relative

Previous macrosomic baby

Member of high risk ethnic group

Age > 25 years

Polycystic ovarian syndrome (PCOS)

Polyhydramnios in previous pregnancy

Previous unexplained perinatal loss / birth of malformed baby

From the above list it can be seen that many of the risk factors for GDM are also risk factors for type 2

diabetes. Also, women of Asian Indian origin are at high risk of GDM even if they do not have any of

the other risk factors.

Implications of GDM

GDM is associated with a host of adverse maternal and fetal implications.

Maternal Implications Fetal Implications

• Pre-eclampsia

• Polyhydramnios

• Operative delivery

• Perineal trauma

•

•

Risk of future diabetes

Ketosis

• Macrosomia

• Birth trauma

• Prematurity

• Respiratory distress syndrome (RDS) even without

prematurity

• Neonatal metabolic complications (Hypoglycemia,

hyperbilirubinemia, polycythemia, hypocalcemia)

• Future risk of diabetes and metabolic syndrome

10

Pre-eclampsia

Women with diabetes during pregnancy are at an increased risk of developing pre-eclampsia. This may be due to insulin resistance or may be associated with a combination of genetic factors, advanced age and high BMI. The rate of pre-eclampsia has been shown to be related to the severity of diabetes.

Risk of Future Diabetes in the Mother

GDM can be regarded as an unmasking of future type 2 diabetes. Following delivery, diabetes usually resolves in most women with GDM but it may persist in 5% to 10%. Another 35% to 60% of these women will develop type 2 diabetes within the next decade. Conversion to diabetes occurs more rapidly and more frequently in high risk ethnic groups such as Asian Indians.

Macrosomia

A macrosomic baby (or “large for gestational age”) is defined as one whose weight is above the 90th percentile for the gestational age. While the western guidelines use a cut-off birth weight of 4.5 kg to define macrosomia, 3.5 kg seems reasonable in the Indian setting.

There are two types of macrosomia- symmetrical and asymmetrical. Infants of mothers with GDM have asymmetrical macrosomia with abnormal thoracic and abdominal circumference, which is larger than the head circumference. Organomegaly is also present .

A macrosomic baby has a high risk of sustaining birth injury such as Erb’s palsy, facial palsy, clavicle fracture and humerus fracture. The risk of shoulder dystocia is also high. Women whose babies are large for gestational age are also more likely to go in for cesarean section. In the long run, individuals who were LGA at birth have a high risk of developing type 2 diabetes in later life.

The pathogenesis of macrosomia is best explained by the Pedersen- Freinkel hypothesis. The maternal blood flowing through the placenta is the sole source of glucose and energy for the fetus. Glucose freely passess across the placental barrier down its concentration gradient. This means that higher the maternal blood glucose, more the glucose received by the fetus. The fetal pancreas responds to this excess supply of glucose and other nutrients (“mixed nutrients”) by secreting more insulin. Hyperinsulinemia, in association with plentiful supply of nutrients, leads to excess growth of fetal tissues and consequently, macrosomia.

It therefore follows that maintaining good control of blood glucose in the mother can limit nutrient

transfer to the fetus and minimize the risk of macrosomia.

Fig. 1.2: The Pedersen hypothesis (modified by Freinkel) suggests that macrosomia develops from excess supply of glucose and other nutrients

(“mixed nutrients”) to the fetus, and consequent hypersecretion of insulin by the fetal pancreas.

Figure 1.2

Certificate Course in Gestational Diabetes Mellitus

Module I: Introduction to Diabetes in Pregnancy

9

Pathogenesis of GDM

GDM develops when the maternal pancreatic beta cell is unable to compensate for the insulin resistance

of late pregnancy by increasing its output of insulin. While the exact nature of the beta cell defect

remains unknown, the following factors may play a role.

Genetic factors

Chronic insulin resistance preceding pregnancy (which would have already worn out the beta cell)

Subclinical inflammation

Since insulin resistance develops only during the second trimester of pregnancy, GDM is very

unlikely to develop before this time. Diabetes diagnosed during the first trimester usually

indicates pre-existing type 2 diabetes rather than GDM.

Risk Factors for GDM

The following have conventionally been considered to be risk factors for GDM:

Obesity

Metabolic syndrome/ diabetes in first degree relative

Previous macrosomic baby

Member of high risk ethnic group

Age > 25 years

Polycystic ovarian syndrome (PCOS)

Polyhydramnios in previous pregnancy

Previous unexplained perinatal loss / birth of malformed baby

From the above list it can be seen that many of the risk factors for GDM are also risk factors for type 2

diabetes. Also, women of Asian Indian origin are at high risk of GDM even if they do not have any of

the other risk factors.

Implications of GDM

GDM is associated with a host of adverse maternal and fetal implications.

Maternal Implications Fetal Implications

• Pre-eclampsia

• Polyhydramnios

• Operative delivery

• Perineal trauma

•

•

Risk of future diabetes

Ketosis

• Macrosomia

• Birth trauma

• Prematurity

• Respiratory distress syndrome (RDS) even without

prematurity

• Neonatal metabolic complications (Hypoglycemia,

hyperbilirubinemia, polycythemia, hypocalcemia)

• Future risk of diabetes and metabolic syndrome

10

Pre-eclampsia

Women with diabetes during pregnancy are at an increased risk of developing pre-eclampsia. This may be due to insulin resistance or may be associated with a combination of genetic factors, advanced age and high BMI. The rate of pre-eclampsia has been shown to be related to the severity of diabetes.

Risk of Future Diabetes in the Mother

GDM can be regarded as an unmasking of future type 2 diabetes. Following delivery, diabetes usually resolves in most women with GDM but it may persist in 5% to 10%. Another 35% to 60% of these women will develop type 2 diabetes within the next decade. Conversion to diabetes occurs more rapidly and more frequently in high risk ethnic groups such as Asian Indians.

Macrosomia

A macrosomic baby (or “large for gestational age”) is defined as one whose weight is above the 90th percentile for the gestational age. While the western guidelines use a cut-off birth weight of 4.5 kg to define macrosomia, 3.5 kg seems reasonable in the Indian setting.

There are two types of macrosomia- symmetrical and asymmetrical. Infants of mothers with GDM have asymmetrical macrosomia with abnormal thoracic and abdominal circumference, which is larger than the head circumference. Organomegaly is also present .

A macrosomic baby has a high risk of sustaining birth injury such as Erb’s palsy, facial palsy, clavicle fracture and humerus fracture. The risk of shoulder dystocia is also high. Women whose babies are large for gestational age are also more likely to go in for cesarean section. In the long run, individuals who were LGA at birth have a high risk of developing type 2 diabetes in later life.

The pathogenesis of macrosomia is best explained by the Pedersen- Freinkel hypothesis. The maternal blood flowing through the placenta is the sole source of glucose and energy for the fetus. Glucose freely passess across the placental barrier down its concentration gradient. This means that higher the maternal blood glucose, more the glucose received by the fetus. The fetal pancreas responds to this excess supply of glucose and other nutrients (“mixed nutrients”) by secreting more insulin. Hyperinsulinemia, in association with plentiful supply of nutrients, leads to excess growth of fetal tissues and consequently, macrosomia.

It therefore follows that maintaining good control of blood glucose in the mother can limit nutrient

transfer to the fetus and minimize the risk of macrosomia.

Fig. 1.2: The Pedersen hypothesis (modified by Freinkel) suggests that macrosomia develops from excess supply of glucose and other nutrients

(“mixed nutrients”) to the fetus, and consequent hypersecretion of insulin by the fetal pancreas.

Figure 1.2

Certificate Course in Gestational Diabetes Mellitus

Module I: Introduction to Diabetes in Pregnancy

11

Hypoglycemia

Neonatal hypoglycemia is a major metabolic problem faced by infants of women with poorly controlled

diabetes (GDM or pre-existing diabetes). As mentioned above, high levels of maternal blood glucose

promote hyperinsulinemia in the fetus, which persist for some time even after the umbilical cord has

been clamped and the supply of glucose terminated. This mismatch between glucose supply and

insulin levels can lead to hypoglycemia in the neonatal period, which is usually transient.

Other Metabolic Problems in the Neonate

Polycythemia occurs due to chronic intrauterine hypoxemia and placental insufficiency secondary to poor glycemic control

As these excess RBCs break down, hyperbilirubinemia occurs days to weeks after birth

The exact mechanism of hypocalcemia is unknown but may be related to functional

hypoparathyroidism

Respiratory Distress Syndrome

Infants of women with poorly controlled diabetes have delayed maturation of their lungs. Pulmonary

surfactant production is found to be decreased due to a combination of hyperglycemia and

hyperinsulinemia. Management of RDS in these babies is complicated by the fact that use of antepartum

steroids for accelerating lung maturity may worsen diabetes control in the mother.

Still Births

The rates of stillbirth are higher in GDM than in the non-diabetic population. The risk of stillbirth

depends on the severity of diabetes and adequacy of glycemic control. If the mean blood glucose

levels are kept between 105-110 mg/dl, the rate of stillbirth approximates that of the non-diabetic

population.

The main causes for stillbirth in GDM are:

Excess fetal growth secondary to hyperglycemia and hyperinsulinemia

Fetal growth restriction

Congenital anomalies are a rare cause of stillbirth in GDM

Congenital anomalies are rare in GDM, since organogenesis is complete by the time at which

GDM usually develops.

Risk of Future Diabetes in the Offspring

Studies in Pima Indians and other ethnic groups have shown that infants exposed to maternal

hyperglycemia during gestation have a high risk of developing type 2 diabetes in later life. Their risk of

developing other components of the metabolic syndrome, such as hypertension, central obesity and

low high density lipoprotein (HDL) cholesterol was also found to be high.

12

Epidemiology of GDM

It is difficult to give a single accurate figure for the worldwide prevalence of GDM, since data is lacking

from many parts of the world, and different authors have used different tests and varying criteria for

the diagnosis of the condition. Nevertheless, it is clear that the prevalence of GDM varies in direct

proportion to the prevalence of type 2 diabetes and impaired glucose tolerance (IGT) in a population.

From the available literature, the prevalence rates of GDM in different countries vary from <1% to more

than 15%.

Data on the prevalence of GDM in India is scanty, but the available literature shows a clear increasing

trend in prevalence. The prevalence rates increased from 2% in 1982 to 7.6% in 1991 and 16.5% in

2002. In a multicentric study from India, the highest prevalence of GDM was found in Tamil Nadu and

the lowest in Kashmir. With the increasing prevalence of type 2 diabetes and IGT in India, the numbers

of women with GDM (and pre-existing diabetes complicating pregnancy) can also be expected to go

up further.

APPENDIXThe criteria for diagnosing diabetes and states of “impaired glucose homeostasis” in non-pregnant

adults are given in Tables 1 and 2, while the currently accepted classification of diabetes is shown in

Table 3.

Table 1: Diagnostic criteria for diabetes in nonpregnant individuals

• Symptoms of diabetes + casual plasma glucose concentration > 200mg/dl (casual - any time of the day without regard to time since last meal)

• Fasting plasma glucose > 126mg/dl* (Fasting - no caloric intake for at least 8 hours)

• 2 Hour plasma glucose during OGTT > 200mg/dl* (OGTT according to WHO criteria)

• HbA1c > 6.5%*

* in the absence of unequivocal hyperglycemia, should be confirmed by retesting on a different day

Table 2: Criteria for diagnosis of states of impaired glucose homeostasis

• Impaired Fasting Glucose (IFG): Fasting Plasma Glucose > 110 and < 126 mg per dL

• Impaired Glucose Tolerance (IGT): 2hr Post Glucose load Plasma Glucose > 140 and < 199 mg per dL

Table 3: Etiologic classification of diabetes mellitus

I. Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)

A. Immune-mediated

B. Idiopathic

II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)

III. Other specific types

A. Genetic defects of beta-cell function

1. Chromosome 12, HNF-1α (MODY 1)

2. Chromosome 7, glucokinase (MODY 2)

3. Chromosome 20, HNF- 4α (MODY 3) Contd...

Certificate Course in Gestational Diabetes Mellitus

Module I: Introduction to Diabetes in Pregnancy

11

Hypoglycemia

Neonatal hypoglycemia is a major metabolic problem faced by infants of women with poorly controlled

diabetes (GDM or pre-existing diabetes). As mentioned above, high levels of maternal blood glucose

promote hyperinsulinemia in the fetus, which persist for some time even after the umbilical cord has

been clamped and the supply of glucose terminated. This mismatch between glucose supply and

insulin levels can lead to hypoglycemia in the neonatal period, which is usually transient.

Other Metabolic Problems in the Neonate

Polycythemia occurs due to chronic intrauterine hypoxemia and placental insufficiency secondary to poor glycemic control

As these excess RBCs break down, hyperbilirubinemia occurs days to weeks after birth

The exact mechanism of hypocalcemia is unknown but may be related to functional

hypoparathyroidism

Respiratory Distress Syndrome

Infants of women with poorly controlled diabetes have delayed maturation of their lungs. Pulmonary

surfactant production is found to be decreased due to a combination of hyperglycemia and

hyperinsulinemia. Management of RDS in these babies is complicated by the fact that use of antepartum

steroids for accelerating lung maturity may worsen diabetes control in the mother.

Still Births

The rates of stillbirth are higher in GDM than in the non-diabetic population. The risk of stillbirth

depends on the severity of diabetes and adequacy of glycemic control. If the mean blood glucose

levels are kept between 105-110 mg/dl, the rate of stillbirth approximates that of the non-diabetic

population.

The main causes for stillbirth in GDM are:

Excess fetal growth secondary to hyperglycemia and hyperinsulinemia

Fetal growth restriction

Congenital anomalies are a rare cause of stillbirth in GDM

Congenital anomalies are rare in GDM, since organogenesis is complete by the time at which

GDM usually develops.

Risk of Future Diabetes in the Offspring

Studies in Pima Indians and other ethnic groups have shown that infants exposed to maternal

hyperglycemia during gestation have a high risk of developing type 2 diabetes in later life. Their risk of

developing other components of the metabolic syndrome, such as hypertension, central obesity and

low high density lipoprotein (HDL) cholesterol was also found to be high.

12

Epidemiology of GDM

It is difficult to give a single accurate figure for the worldwide prevalence of GDM, since data is lacking

from many parts of the world, and different authors have used different tests and varying criteria for

the diagnosis of the condition. Nevertheless, it is clear that the prevalence of GDM varies in direct

proportion to the prevalence of type 2 diabetes and impaired glucose tolerance (IGT) in a population.

From the available literature, the prevalence rates of GDM in different countries vary from <1% to more

than 15%.

Data on the prevalence of GDM in India is scanty, but the available literature shows a clear increasing

trend in prevalence. The prevalence rates increased from 2% in 1982 to 7.6% in 1991 and 16.5% in

2002. In a multicentric study from India, the highest prevalence of GDM was found in Tamil Nadu and

the lowest in Kashmir. With the increasing prevalence of type 2 diabetes and IGT in India, the numbers

of women with GDM (and pre-existing diabetes complicating pregnancy) can also be expected to go

up further.

APPENDIXThe criteria for diagnosing diabetes and states of “impaired glucose homeostasis” in non-pregnant

adults are given in Tables 1 and 2, while the currently accepted classification of diabetes is shown in

Table 3.

Table 1: Diagnostic criteria for diabetes in nonpregnant individuals

• Symptoms of diabetes + casual plasma glucose concentration > 200mg/dl (casual - any time of the day without regard to time since last meal)

• Fasting plasma glucose > 126mg/dl* (Fasting - no caloric intake for at least 8 hours)

• 2 Hour plasma glucose during OGTT > 200mg/dl* (OGTT according to WHO criteria)

• HbA1c > 6.5%*

* in the absence of unequivocal hyperglycemia, should be confirmed by retesting on a different day

Table 2: Criteria for diagnosis of states of impaired glucose homeostasis

• Impaired Fasting Glucose (IFG): Fasting Plasma Glucose > 110 and < 126 mg per dL

• Impaired Glucose Tolerance (IGT): 2hr Post Glucose load Plasma Glucose > 140 and < 199 mg per dL

Table 3: Etiologic classification of diabetes mellitus

I. Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)

A. Immune-mediated

B. Idiopathic

II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)

III. Other specific types

A. Genetic defects of beta-cell function

1. Chromosome 12, HNF-1α (MODY 1)

2. Chromosome 7, glucokinase (MODY 2)

3. Chromosome 20, HNF- 4α (MODY 3) Contd...

Certificate Course in Gestational Diabetes Mellitus

Module I: Introduction to Diabetes in Pregnancy

13

Take Home Messages

Pregnancy is a diabetogenic state

GDM results when the beta cell is unable to adapt to the diabetogenic milieu of pregnancy

The prevalence of GDM is high in India

Diabetes in pregnancy is associated with serious consequences to the baby as well as the mother, if early detection and appropriate treatment are not offered

Table 3: Etiologic classification of diabetes mellitus

4. Chromosome 13, IPF-1 (MODY 4)

5. Chromosome 17, HNF-1β (MODY 5)

6. Chromosome 2, NeuroD1 (MODY 6)

7. Mitochondrial DNA

8. Others

B. Genetic defects in insulin action

1. Type A insulin resistance

2. Leprechaunism

3. Rabson- Mendenhall syndrome

4. Lipoatrophic diabetes

5. Others

C. Diseases of exocrine pancreas

Pancreatitis

Trauma/pancreatectomy

Neoplasia

Cystic fibrosis

Hemochromatosis

Fibrocalculous pancreatopathy

Others

D. Endocrinopathies

Acromegaly

Cushing’s syndrome

Glucagonoma

Pheochromocytoma

Hyperthyroidism

Somatostatinoma

Aldosteronoma

Others

E. Drug- or chemical-induced

Vacor

Pentamidine

Nicotinic acid

F. Infections

G. Uncommon forms of immune-mediated diabetes

H. Other genetic syndromes sometimes associated with diabetes

IV. Gestational diabetes

14

Module I: Introduction to Diabetes in Pregnancy

13

Take Home Messages

Pregnancy is a diabetogenic state

GDM results when the beta cell is unable to adapt to the diabetogenic milieu of pregnancy

The prevalence of GDM is high in India

Diabetes in pregnancy is associated with serious consequences to the baby as well as the mother, if early detection and appropriate treatment are not offered

Table 3: Etiologic classification of diabetes mellitus

4. Chromosome 13, IPF-1 (MODY 4)

5. Chromosome 17, HNF-1β (MODY 5)

6. Chromosome 2, NeuroD1 (MODY 6)

7. Mitochondrial DNA

8. Others

B. Genetic defects in insulin action

1. Type A insulin resistance

2. Leprechaunism

3. Rabson- Mendenhall syndrome

4. Lipoatrophic diabetes

5. Others

C. Diseases of exocrine pancreas

Pancreatitis

Trauma/pancreatectomy

Neoplasia

Cystic fibrosis

Hemochromatosis

Fibrocalculous pancreatopathy

Others

D. Endocrinopathies

Acromegaly

Cushing’s syndrome

Glucagonoma

Pheochromocytoma

Hyperthyroidism

Somatostatinoma

Aldosteronoma

Others

E. Drug- or chemical-induced

Vacor

Pentamidine

Nicotinic acid

F. Infections

G. Uncommon forms of immune-mediated diabetes

H. Other genetic syndromes sometimes associated with diabetes

IV. Gestational diabetes

14

Powerpoint Presentations

LEARNING OBJECTIVES

• Learn about the evolution of the concept of diabetes in pregnancy

• Review the metabolic alterations occurring in pregnancy and how these can lead to diabetes

• Define GDM and discuss its epidemiology

• Learn about the consequences of GDM to the mother and fetus

• Understand the great public health significance of GDM

Slide 2

Slide 1

15

HISTORICAL PERSPECTIVE

OF GDM

Slide 3

Notes:

Notes:

Notes:

INTRODUCTION TO

DIABETES IN PREGNANCY

SAFES 2014-16

SAFES 2014-16

Certificate Course in Gestational Diabetes Mellitus

16

Slide 4

DIABETES IN PREGNANCY

The Early Days

Pre-insulin era

• Pregnancy in untreated diabetes was almost unknown

• “True diabetes was inconsistent with conception” (Blott, Paris, 1856)- a

statement probably prompted by the short lifespan of women with type

1 diabetes (the major cause of pre-gestational diabetes in women of

reproductive age in that era)

• Abortion and IUD were quite frequent

• Major risk was the death of the mother during, or soon after, pregnancy

due to uncontrolled diabetes

• Overall maternal mortality was also high in that era

PRISCILLA WHITE (1900-1989)

The Doyenne of Diabetic Pregnancy

• Identified the link between diabetes

duration, vascular complications and

outcomes in pre-existing diabetes

complicating pregnancy

• Introduced the world-famous White

classification of diabetes in pregnancy in

1949

• However, this classification did not

include GDM as a separate entity until

1980

Slide 5

DIABETES AND PREGNANCY

The Concept of Gestational Diabetes

While the first case of “GDM” was reported by Bennewitz

in Germany in 1853 (he considered diabetes a “symptom of

pregnancy” and noted that glycosuria resolved after delivery),

the concept itself is relatively recent

Contd…

Slide 6

Notes:

Notes:

Notes:

Powerpoint Presentations

LEARNING OBJECTIVES

• Learn about the evolution of the concept of diabetes in pregnancy

• Review the metabolic alterations occurring in pregnancy and how these can lead to diabetes

• Define GDM and discuss its epidemiology

• Learn about the consequences of GDM to the mother and fetus

• Understand the great public health significance of GDM

Slide 2

Slide 1

15

HISTORICAL PERSPECTIVE

OF GDM

Slide 3

Notes:

Notes:

Notes:

INTRODUCTION TO

DIABETES IN PREGNANCY

SAFES 2014-16

SAFES 2014-16

Certificate Course in Gestational Diabetes Mellitus

16

Slide 4

DIABETES IN PREGNANCY

The Early Days

Pre-insulin era

• Pregnancy in untreated diabetes was almost unknown

• “True diabetes was inconsistent with conception” (Blott, Paris, 1856)- a

statement probably prompted by the short lifespan of women with type

1 diabetes (the major cause of pre-gestational diabetes in women of

reproductive age in that era)

• Abortion and IUD were quite frequent

• Major risk was the death of the mother during, or soon after, pregnancy

due to uncontrolled diabetes

• Overall maternal mortality was also high in that era

PRISCILLA WHITE (1900-1989)

The Doyenne of Diabetic Pregnancy

• Identified the link between diabetes

duration, vascular complications and

outcomes in pre-existing diabetes

complicating pregnancy

• Introduced the world-famous White

classification of diabetes in pregnancy in

1949

• However, this classification did not

include GDM as a separate entity until

1980

Slide 5

DIABETES AND PREGNANCY

The Concept of Gestational Diabetes

While the first case of “GDM” was reported by Bennewitz

in Germany in 1853 (he considered diabetes a “symptom of

pregnancy” and noted that glycosuria resolved after delivery),

the concept itself is relatively recent

Contd…

Slide 6

Notes:

Notes:

Notes:

• 1999 - WHO criteria for diagnosis of GDM introduced

• 2005 - ACHOIS Study underlined the benefits of treating GDM

• 2006 - DIPSI Guidelines published

• 2008 - HAPO Study findings published

• 2010 - IADPSG revises the diagnostic criteria for GDM

• 2012 - ADA endorses IADPSG Criteria

• 2013 - NIH states that more evidence is needed before

IADPSG criteria are adopted

2014 - WHO has adopted IADPSG criteria and dropped

their own 1999 criteria.

Slide 8

• 1940s - First recognition that maternal hyperglycemia

influences pregnancy outcomes

• 1952 - Jorgen Pedersen puts forward the hyperglycemia -

hyperinsulinemia hypothesis to explain fetal macrosomia

(later termed the Pedersen Hypothesis)

• 1961 - John B. O’Sullivan introduced the term “Gestational

Diabetes Mellitus” (GDM)

• 1964 - O’Sullivan and Mahan criteria for diagnosing GDM

introduced; these were later modified by Carpenter and

Coustan

• Early 1970s - Norbert Freinkel introduces the terms “facilitated

anabolism” and “accelerated starvation”Contd…

Slide 7

DIAGNOSTIC CRITERIA FOR DIABETES

(in nonpregnant adults)

• Symptoms of diabetes + casual plasma glucose concentration > 200mg/dl

(casual - any time of the day without regard to time since last meal)

• Fasting plasma glucose > 126mg/dl* (Fasting - no caloric intake for at least 8 hours)

• 2 Hour plasma glucose during OGTT > 200mg/dl* (OGTT according to WHO criteria)

• HbA1c > 6.5%*

*In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing

Slide 9

17

Module I: Introduction to Diabetes in Pregnancy

Notes:

Notes:

Notes:

•

CRITERIA FOR THE DIAGNOSIS OF

IMPAIRED GLUCOSE HOMEOSTASIS

Impaired glucose homeostasis

Impaired Fasting Glucose (IFG):

Fasting Plasma Glucose > 110 and < 126 mg per dL

Impaired Glucose Tolerance (IGT):

2hr Post Glucose load Plasma Glucose > 140 and < 199 mg per dL

World Health Organisation, 2006

Slide 10

18

CASE STUDY 2

A 35 year old nongravid female with a strong family history

of diabetes undergoes an OGTT. The following are her results

Time 0 hr (Fasting) 2 hour

Glucose (mg/dl) 98 177

What is the diagnosis?

Slide 12

CASE STUDY 1

A 28 year old nongravid female has an OGTT performed as

part of insurance screening. The following are her results

Time 0 hr (Fasting) 2 hour

Glucose (mg/dl) 115 208

What is the diagnosis?

Slide 11

Notes:

Notes:

Notes:

Certificate Course in Gestational Diabetes Mellitus

• 1999 - WHO criteria for diagnosis of GDM introduced

• 2005 - ACHOIS Study underlined the benefits of treating GDM

• 2006 - DIPSI Guidelines published

• 2008 - HAPO Study findings published

• 2010 - IADPSG revises the diagnostic criteria for GDM

• 2012 - ADA endorses IADPSG Criteria

• 2013 - NIH states that more evidence is needed before

IADPSG criteria are adopted

2014 - WHO has adopted IADPSG criteria and dropped

their own 1999 criteria.

Slide 8

• 1940s - First recognition that maternal hyperglycemia

influences pregnancy outcomes

• 1952 - Jorgen Pedersen puts forward the hyperglycemia -

hyperinsulinemia hypothesis to explain fetal macrosomia

(later termed the Pedersen Hypothesis)

• 1961 - John B. O’Sullivan introduced the term “Gestational

Diabetes Mellitus” (GDM)

• 1964 - O’Sullivan and Mahan criteria for diagnosing GDM

introduced; these were later modified by Carpenter and

Coustan

• Early 1970s - Norbert Freinkel introduces the terms “facilitated

anabolism” and “accelerated starvation”Contd…

Slide 7

DIAGNOSTIC CRITERIA FOR DIABETES

(in nonpregnant adults)

• Symptoms of diabetes + casual plasma glucose concentration > 200mg/dl

(casual - any time of the day without regard to time since last meal)

• Fasting plasma glucose > 126mg/dl* (Fasting - no caloric intake for at least 8 hours)

• 2 Hour plasma glucose during OGTT > 200mg/dl* (OGTT according to WHO criteria)

• HbA1c > 6.5%*

*In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing

Slide 9

17

Module I: Introduction to Diabetes in Pregnancy

Notes:

Notes:

Notes:

•

CRITERIA FOR THE DIAGNOSIS OF

IMPAIRED GLUCOSE HOMEOSTASIS

Impaired glucose homeostasis

Impaired Fasting Glucose (IFG):

Fasting Plasma Glucose > 110 and < 126 mg per dL

Impaired Glucose Tolerance (IGT):

2hr Post Glucose load Plasma Glucose > 140 and < 199 mg per dL

World Health Organisation, 2006

Slide 10

18

CASE STUDY 2

A 35 year old nongravid female with a strong family history

of diabetes undergoes an OGTT. The following are her results

Time 0 hr (Fasting) 2 hour

Glucose (mg/dl) 98 177

What is the diagnosis?

Slide 12

CASE STUDY 1

A 28 year old nongravid female has an OGTT performed as

part of insurance screening. The following are her results

Time 0 hr (Fasting) 2 hour

Glucose (mg/dl) 115 208

What is the diagnosis?

Slide 11

Notes:

Notes:

Notes:

Certificate Course in Gestational Diabetes Mellitus

19

Module I: Introduction to Diabetes in Pregnancy

ETIOLOGIC CLASSIFICATION OF

DIABETES MELLITUS(ADA Expert Committee- 1997)

Includes four clinical classes

• Type 1 diabetes ( cell destruction, usually leading to absolute insulin deficiency )

a. Immune mediated b. Idiopathic

• Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)

Contd…

Slide 13

ETIOLOGIC CLASSIFICATION OF

DIABETES MELLITUS

• Other specific types

▪ Genetic defects of cell function (e.g. MODY) ▪ Genetic defects in insulin action

▪ Diseases of the exocrine pancreas

▪ Endocrinopathies

▪ Drug - or chemical induced

▪ Infections

▪ Uncommon forms of immune-mediated diabetes

▪ Other genetic syndromes sometimes associated with diabetes

• Gestational Diabetes Mellitus (GDM)

Slide 14

GESTATIONAL DIABETES MELLITUS

Definition

“Glucose intolerance of any severity with onset or first

recognition during pregnancy”

Metzger BE et al. Diabetes Care, 1998

Contd...

Slide 15

Notes:

Notes:

Notes:

GESTATIONAL DIABETES MELLITUS

Definition

• This definition is applicable irrespective of whether insulin is used or not for treatment

• It is also applicable irrespective of whether the condition resolves after delivery

• It does not exclude the possibility that diabetes could have antedated the pregnancy

Contd…

Slide 16

Notes:

Notes:

Notes:

20

GESTATIONAL DIABETES MELLITUS

Definition

Women diagnosed with GDM might have:

• Normal glucose tolerance prior to pregnancy which becomes abnormal with pregnancy and returns to normal following delivery

• Mild glucose intolerance (“pre-diabetes”) before pregnancy which worsens during pregnancy

• Previously undiagnosed type 2 diabetes

• Previously undiagnosed type 1 diabetes (rare)

• Previously undiagnosed MODY and secondary diabetes (rare)

Slide 17

PATHOGENESIS OF GDM

Slide 18

Certificate Course in Gestational Diabetes Mellitus

SAFES 2014-16

19

Module I: Introduction to Diabetes in Pregnancy

ETIOLOGIC CLASSIFICATION OF

DIABETES MELLITUS(ADA Expert Committee- 1997)

Includes four clinical classes

• Type 1 diabetes ( cell destruction, usually leading to absolute insulin deficiency )

a. Immune mediated b. Idiopathic

• Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)

Contd…

Slide 13

ETIOLOGIC CLASSIFICATION OF

DIABETES MELLITUS

• Other specific types

▪ Genetic defects of cell function (e.g. MODY) ▪ Genetic defects in insulin action

▪ Diseases of the exocrine pancreas

▪ Endocrinopathies

▪ Drug - or chemical induced

▪ Infections

▪ Uncommon forms of immune-mediated diabetes

▪ Other genetic syndromes sometimes associated with diabetes

• Gestational Diabetes Mellitus (GDM)

Slide 14

GESTATIONAL DIABETES MELLITUS

Definition

“Glucose intolerance of any severity with onset or first

recognition during pregnancy”

Metzger BE et al. Diabetes Care, 1998

Contd...

Slide 15

Notes:

Notes:

Notes:

GESTATIONAL DIABETES MELLITUS

Definition

• This definition is applicable irrespective of whether insulin is used or not for treatment

• It is also applicable irrespective of whether the condition resolves after delivery

• It does not exclude the possibility that diabetes could have antedated the pregnancy

Contd…

Slide 16

Notes:

Notes:

Notes:

20

GESTATIONAL DIABETES MELLITUS

Definition

Women diagnosed with GDM might have:

• Normal glucose tolerance prior to pregnancy which becomes abnormal with pregnancy and returns to normal following delivery

• Mild glucose intolerance (“pre-diabetes”) before pregnancy which worsens during pregnancy

• Previously undiagnosed type 2 diabetes

• Previously undiagnosed type 1 diabetes (rare)

• Previously undiagnosed MODY and secondary diabetes (rare)

Slide 17

PATHOGENESIS OF GDM

Slide 18

Certificate Course in Gestational Diabetes Mellitus

SAFES 2014-16

21

Module I: Introduction to Diabetes in Pregnancy

MATERNO - FETAL NUTRIENT TRANSFER

• The fetus is dependent on the maternal supply of nutrients for all it’s requirements

• Nutrients from the maternal circulation cross the placental barrier and reach the fetus

• This process is primarily dependent on the materno-fetal concentration gradient of the nutrient in question

Slide 20

EFFECT OF PREGNANCY ON

BLOOD GLUCOSE

• Pregnancy is characterised by profound metabolic alterations in the mother

• The main purpose of these changes is to ensure adequate nutrition (in the form of glucose) to the growing fetus during times of plenty as well as times of scarcity

• At the same time, the metabolic demands of the mother also need to be met

Slide 19

MATERNO - FETAL NUTRIENT TRANSFER

Glucose

Mother Placenta Fetus

Glucose

Amino Acids Amino Acids

Ketones Ketones

Triglycerides Fatty Acids

Insulin

Glucagon

Glucose and amino acids traverse the placenta while insulin does not

Freinkel N. Diabetes, 1980

Slide 21

Notes:

Notes:

Note: A schematic representation of

maternal-fetal nutrient and hormone

exchange across the placenta in pregnancy.

Glucose, amino acids, and ketones move

freely into the fetal circulation, whereas

insulin does not. Glucose travels down its

concentration gradient while amino acids

are transported against their concentration

gradient (their levels are higher in fetal

blood than in maternal blood).Maternal

hyperglycemia and ketosis are thus

reflected in the fetal circulation. (Freinkel N,

Diabetes, 1980)

22

Metabolism during pregnancy is best described as a

combination of “facilitated anabolism” and “accelerated

starvation (catabolism)”

Buchanan TA, Coustan DR. Diabetes mellitus. In: Medical complications during pregnancy, 4th ed.

Philadelphia: WB Saunders,1994

Slide 22

Notes:

Note: The figure schematically represents

maternal metabolic changes during

gestation. Anabolism during feeding and

catabolism during fasting are exaggerated in

a progressive fashion, reflecting the

combined effects of placental hormones and

nutrient use by the fetus

EARLY PREGNANCY

Facilitated Anabolism

Increased glycogenesisReduced hepatic glucose output

This leads to a reduction in fasting plasma glucose levels in early pregnancyContd…

Increased peripheral glucose uptake Increased lipid synthesis

Hyperinsulinism Increased insulin sensitivity

Slide 24

EARLY PREGNANCY

Facilitated Anabolism

• Main hormones involved are estrogen and progesterone

• These hormones cause hyperinsulinemia by promoting beta cell hyperplasia and increased insulin release

• During early pregnancy, the first phase insulin secretion is found to be augmented when compared to pre-gravid state; however, second phase secretion remains unchanged

Contd…

Slide 23

Note: During early pregnancy, insulin

resistance is low while beta cell function is

normal or increased. This leads to low plasma

glucose levels as well as HbA1c till around the

20th week of pregnancy. The placental

transfer of glucose to the growing fetus is

another important reason for lowering of

maternal glucose levels

Certificate Course in Gestational Diabetes Mellitus

21

Module I: Introduction to Diabetes in Pregnancy

MATERNO - FETAL NUTRIENT TRANSFER

• The fetus is dependent on the maternal supply of nutrients for all it’s requirements

• Nutrients from the maternal circulation cross the placental barrier and reach the fetus

• This process is primarily dependent on the materno-fetal concentration gradient of the nutrient in question

Slide 20

EFFECT OF PREGNANCY ON

BLOOD GLUCOSE

• Pregnancy is characterised by profound metabolic alterations in the mother

• The main purpose of these changes is to ensure adequate nutrition (in the form of glucose) to the growing fetus during times of plenty as well as times of scarcity

• At the same time, the metabolic demands of the mother also need to be met

Slide 19

MATERNO - FETAL NUTRIENT TRANSFER

Glucose

Mother Placenta Fetus

Glucose

Amino Acids Amino Acids

Ketones Ketones

Triglycerides Fatty Acids

Insulin

Glucagon

Glucose and amino acids traverse the placenta while insulin does not

Freinkel N. Diabetes, 1980

Slide 21

Notes:

Notes:

Note: A schematic representation of

maternal-fetal nutrient and hormone

exchange across the placenta in pregnancy.

Glucose, amino acids, and ketones move

freely into the fetal circulation, whereas

insulin does not. Glucose travels down its

concentration gradient while amino acids

are transported against their concentration

gradient (their levels are higher in fetal

blood than in maternal blood).Maternal

hyperglycemia and ketosis are thus

reflected in the fetal circulation. (Freinkel N,

Diabetes, 1980)

22

Metabolism during pregnancy is best described as a

combination of “facilitated anabolism” and “accelerated

starvation (catabolism)”

Buchanan TA, Coustan DR. Diabetes mellitus. In: Medical complications during pregnancy, 4th ed.

Philadelphia: WB Saunders,1994

Slide 22

Notes:

Note: The figure schematically represents

maternal metabolic changes during

gestation. Anabolism during feeding and

catabolism during fasting are exaggerated in

a progressive fashion, reflecting the

combined effects of placental hormones and

nutrient use by the fetus

EARLY PREGNANCY

Facilitated Anabolism

Increased glycogenesisReduced hepatic glucose output

This leads to a reduction in fasting plasma glucose levels in early pregnancyContd…

Increased peripheral glucose uptake Increased lipid synthesis

Hyperinsulinism Increased insulin sensitivity

Slide 24

EARLY PREGNANCY

Facilitated Anabolism

• Main hormones involved are estrogen and progesterone

• These hormones cause hyperinsulinemia by promoting beta cell hyperplasia and increased insulin release

• During early pregnancy, the first phase insulin secretion is found to be augmented when compared to pre-gravid state; however, second phase secretion remains unchanged

Contd…

Slide 23

Note: During early pregnancy, insulin

resistance is low while beta cell function is

normal or increased. This leads to low plasma

glucose levels as well as HbA1c till around the

20th week of pregnancy. The placental

transfer of glucose to the growing fetus is

another important reason for lowering of

maternal glucose levels

Certificate Course in Gestational Diabetes Mellitus

23

EARLY PREGNANCY

Facilitated Anabolism

• Main purpose is to prepare the mother for the increased energy demands expected during later pregnancy

• During early pregnancy, energy demands from the fetus are relatively low since linear growth is not as rapid as it will be subsequently

Slide 25

EARLY PREGNANCY

Since insulin sensitivity is normal or raised during early

pregnancy and insulin secretion is increased, GDM is rare

during this period

Women diagnosed to have “GDM” during early pregnancy may

have had hitherto undiagnosed type 2 diabetes

Slide 26

LATER PREGNANCY

Stage of Insulin Resistance

• After 20 weeks of gestation, the placental hormones start playing an increasingly important role

• The main placental hormone contributing to insulin resistance is human placental lactogen (HPL)

• Other hormones involved are prolactin, cortisol, progesterone and growth hormone

• All of these hormones antagonise the effect of insulin and bring about a state of physiological insulin resistance

Contd...

Slide 27

Notes:

Notes:

Notes:

Module I: Introduction to Diabetes in Pregnancy

LATER PREGNANCY

Stage of Insulin Resistance

Increased levels of placental hormonesInsulin resistance

Facilitated diffusion following a meal

Higher blood glucose levels- enable free diffusion to fetus to

meet its increased demands

Accelerated starvation in the fasting state

High levels of free fatty acids and ketone bodies to provide

fuel for the mother, so that glucose is spared for the fetus

Slide 28

First-phase insulin response (minutes 1–10 of intravenous

glucose tolerance test) in normal women and women who

developed GDM

Buchanan TA et al, Diabetes Rev, 1995

Slide 29

Insulin sensitivity during different stages of pregnancy in

women with and without GDM

Catalano PM et al, Am J Obstetr Gynecol, 1999

Slide 30

Notes:

Note: Buchanan and Catalano used

euglycemic, hyperinsulinemic clamps and

intravenous glucose tolerance tests to

measure insulin sensitivity and secretion in

normal women and in those with GDM

before and during early and late pregnancy.

Their results demonstrate increasing insulin

secretion in both groups, but a much flatter

slope in the women with GDM [despite the

fact that insulin resistance was somewhat

greater in the women with GDM]

Note: Although insulin secretory defect

(failure of compensation) underlies most

cases of GDM, it is also noteworthy that

women with GDM tend to have lower insulin

sensitivity during all stages of pregnancy as

well as in the pre-gravid state.

Certificate Course in Gestational Diabetes Mellitus

24

23

EARLY PREGNANCY

Facilitated Anabolism

• Main purpose is to prepare the mother for the increased energy demands expected during later pregnancy

• During early pregnancy, energy demands from the fetus are relatively low since linear growth is not as rapid as it will be subsequently

Slide 25

EARLY PREGNANCY

Since insulin sensitivity is normal or raised during early

pregnancy and insulin secretion is increased, GDM is rare

during this period

Women diagnosed to have “GDM” during early pregnancy may

have had hitherto undiagnosed type 2 diabetes

Slide 26

LATER PREGNANCY

Stage of Insulin Resistance

• After 20 weeks of gestation, the placental hormones start playing an increasingly important role

• The main placental hormone contributing to insulin resistance is human placental lactogen (HPL)

• Other hormones involved are prolactin, cortisol, progesterone and growth hormone

• All of these hormones antagonise the effect of insulin and bring about a state of physiological insulin resistance

Contd...

Slide 27

Notes:

Notes:

Notes:

Module I: Introduction to Diabetes in Pregnancy

LATER PREGNANCY

Stage of Insulin Resistance

Increased levels of placental hormonesInsulin resistance

Facilitated diffusion following a meal

Higher blood glucose levels- enable free diffusion to fetus to

meet its increased demands

Accelerated starvation in the fasting state

High levels of free fatty acids and ketone bodies to provide

fuel for the mother, so that glucose is spared for the fetus

Slide 28

First-phase insulin response (minutes 1–10 of intravenous

glucose tolerance test) in normal women and women who

developed GDM

Buchanan TA et al, Diabetes Rev, 1995

Slide 29

Insulin sensitivity during different stages of pregnancy in

women with and without GDM

Catalano PM et al, Am J Obstetr Gynecol, 1999

Slide 30

Notes:

Note: Buchanan and Catalano used

euglycemic, hyperinsulinemic clamps and

intravenous glucose tolerance tests to

measure insulin sensitivity and secretion in

normal women and in those with GDM

before and during early and late pregnancy.

Their results demonstrate increasing insulin

secretion in both groups, but a much flatter

slope in the women with GDM [despite the

fact that insulin resistance was somewhat

greater in the women with GDM]

Note: Although insulin secretory defect

(failure of compensation) underlies most

cases of GDM, it is also noteworthy that

women with GDM tend to have lower insulin

sensitivity during all stages of pregnancy as

well as in the pre-gravid state.

Certificate Course in Gestational Diabetes Mellitus

24

WHY DOES THE BETA CELL FAIL TO ADAPT?

• Genetic factors

• Chronic insulin resistance antedating pregnancy (especially in obese women)

• Subclinical inflammation

Slide 32

PATHOGENESIS OF GDM

• In most women, the beta cell can compensate for the increased insulin resistance of pregnancy by hyperplasia and hypertrophy (Van Assche et al, 1978)

• Third trimester fasting insulin levels are 2 fold higher than pre-pregnant levels in normal pregnant women

• This results in fasting blood glucose levels that are 10 to 20 mg/dl lower than in the nonpregnant state, even in the last trimester (Kalhan SC, 1979; Metzger BE, 1982; Buchanan TA, 1990; Catalano PM, 1992)

GDM develops when the beta cell is unable to compensate for the increased insulin resistance

Slide 31

RISK FACTORS OF GDM

Slide 33

Module I: Introduction to Diabetes in Pregnancy

25

Notes:

Notes:

Notes:

SAFES 2014-16

CASE STUDY 3

Mrs. C is a 22 year old primigravida. She is 156 cm tall and weighs 51 Kg (BMI 20.9 Kg/m2). She has no family history of diabetes.

What is her risk of developing GDM?

Slide 34

GDM

Risk Factors

• Obesity (BMI >25) and Metabolic syndrome

• Diabetes in first degree relative

• Previous GDM or glucose intolerance

• Previous macrosomic baby

• Member of high risk ethnic group (all Indians fall in this category)

• Age >25

• Polycystic Ovarian Syndrome (PCOS)

• Previous polyhydramnios

• Previous unexplained perinatal loss or birth of a malformed infant

Slide 36

CASE STUDY 4

Mrs. C is 33 years old. She has suffered from two miscarriages in the last three years and has earlier delivered a baby weighing 4.1 Kg. She is 160 cm tall and weighs 81 Kg (BMI 31.6 Kg/m2). Both her parents have diabetes.

What is her risk of developing GDM?

Slide 35

Notes:

Notes:

Note: The risk factors for GDM are listed

above. It can be easily appreciated that

most pregnant women will have one or

more of these risk factors

Certificate Course in Gestational Diabetes Mellitus

26

WHY DOES THE BETA CELL FAIL TO ADAPT?

• Genetic factors

• Chronic insulin resistance antedating pregnancy (especially in obese women)

• Subclinical inflammation

Slide 32

PATHOGENESIS OF GDM

• In most women, the beta cell can compensate for the increased insulin resistance of pregnancy by hyperplasia and hypertrophy (Van Assche et al, 1978)

• Third trimester fasting insulin levels are 2 fold higher than pre-pregnant levels in normal pregnant women

• This results in fasting blood glucose levels that are 10 to 20 mg/dl lower than in the nonpregnant state, even in the last trimester (Kalhan SC, 1979; Metzger BE, 1982; Buchanan TA, 1990; Catalano PM, 1992)

GDM develops when the beta cell is unable to compensate for the increased insulin resistance

Slide 31

RISK FACTORS OF GDM

Slide 33

Module I: Introduction to Diabetes in Pregnancy

25

Notes:

Notes:

Notes:

SAFES 2014-16

CASE STUDY 3

Mrs. C is a 22 year old primigravida. She is 156 cm tall and weighs 51 Kg (BMI 20.9 Kg/m2). She has no family history of diabetes.

What is her risk of developing GDM?

Slide 34

GDM

Risk Factors

• Obesity (BMI >25) and Metabolic syndrome

• Diabetes in first degree relative

• Previous GDM or glucose intolerance

• Previous macrosomic baby

• Member of high risk ethnic group (all Indians fall in this category)

• Age >25

• Polycystic Ovarian Syndrome (PCOS)

• Previous polyhydramnios

• Previous unexplained perinatal loss or birth of a malformed infant

Slide 36

CASE STUDY 4

Mrs. C is 33 years old. She has suffered from two miscarriages in the last three years and has earlier delivered a baby weighing 4.1 Kg. She is 160 cm tall and weighs 81 Kg (BMI 31.6 Kg/m2). Both her parents have diabetes.

What is her risk of developing GDM?

Slide 35

Notes:

Notes:

Note: The risk factors for GDM are listed

above. It can be easily appreciated that

most pregnant women will have one or

more of these risk factors

Certificate Course in Gestational Diabetes Mellitus

26

Module I: Introduction to Diabetes in Pregnancy

27

CONGENITAL MALFORMATIONS IN GDM

Congenital malformations are extremely uncommon in

GDM, since it usually develops in late pregnancy, long after

organogenesis is complete

Risk of malformation is similar to that in women with pre

existing diabetes if GDM is diagnosed in the first trimester

Slide 39

IMPLICATIONS OF GDM

Slide 37

Fetal and Neonatal implications

• Fetal macrosomia

• Birth trauma

• Prematurity

• RDS even without prematurity

• Neonatal metabolic complications (hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia)

• Obesity and diabetes in later life

Maternal implications

• Pre-eclampsia

• Polyhydramnios

• Operative delivery

• Perineal trauma

• Risk of future diabetes

Ketosis

Slide 38

Notes:

Notes:

Notes:

•

IMPLICATIONS OF GDM

SAFES 2014-16

28

MACROSOMIA

• A macrosomic baby is one whose weight is above the 90th

percentile for the gestational age

• Also termed “large for gestational age (LGA)”

• The American College of Obstetricians and Gynecologists prefers a cut off of 4.5 kg to define a macrosomic baby

• No validated cut offs for India - 3.5 kg seems reasonable (3.45 kg corresponds to the 90th percentile of birth weight for Indians)

Contd…

Slide 40

Certificate Course in Gestational Diabetes Mellitus

MACROSOMIA

• High risk of birth trauma (shoulder dystocia, clavicle fracture, humerus fracture, brachial palsy, facial palsy)

• Increased risk of C-section

• Increased risk of diabetes in later life

Slide 42

Notes:

Notes:

Notes:

MACROSOMIA

Slide 41

• Infants of mothers with GDM have asymmetrical macrosomia with abnormal thoracic and abdominal circumference which is larger than head circumference

• Organomegaly is also present

• In untreated GDM, the risk of macrosomia is as high as 40% (Persson and Hanson, Diabetes Care, 1998)

• Severe maternal diabetes (particularly type 1 DM) with vasculopathy and impaired renal function may be associated with intrauterine growth restriction and microsomia (Van Assche et al, Br Med Bull, 2001)

Contd…

Module I: Introduction to Diabetes in Pregnancy

27

CONGENITAL MALFORMATIONS IN GDM

Congenital malformations are extremely uncommon in

GDM, since it usually develops in late pregnancy, long after

organogenesis is complete

Risk of malformation is similar to that in women with pre

existing diabetes if GDM is diagnosed in the first trimester

Slide 39

IMPLICATIONS OF GDM

Slide 37

Fetal and Neonatal implications

• Fetal macrosomia

• Birth trauma

• Prematurity

• RDS even without prematurity

• Neonatal metabolic complications (hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia)

• Obesity and diabetes in later life

Maternal implications

• Pre-eclampsia

• Polyhydramnios

• Operative delivery

• Perineal trauma

• Risk of future diabetes

Ketosis

Slide 38

Notes:

Notes:

Notes:

•

IMPLICATIONS OF GDM

SAFES 2014-16

28

MACROSOMIA

• A macrosomic baby is one whose weight is above the 90th

percentile for the gestational age

• Also termed “large for gestational age (LGA)”

• The American College of Obstetricians and Gynecologists prefers a cut off of 4.5 kg to define a macrosomic baby

• No validated cut offs for India - 3.5 kg seems reasonable (3.45 kg corresponds to the 90th percentile of birth weight for Indians)

Contd…

Slide 40

Certificate Course in Gestational Diabetes Mellitus

MACROSOMIA

• High risk of birth trauma (shoulder dystocia, clavicle fracture, humerus fracture, brachial palsy, facial palsy)

• Increased risk of C-section

• Increased risk of diabetes in later life

Slide 42

Notes:

Notes:

Notes:

MACROSOMIA

Slide 41

• Infants of mothers with GDM have asymmetrical macrosomia with abnormal thoracic and abdominal circumference which is larger than head circumference

• Organomegaly is also present

• In untreated GDM, the risk of macrosomia is as high as 40% (Persson and Hanson, Diabetes Care, 1998)

• Severe maternal diabetes (particularly type 1 DM) with vasculopathy and impaired renal function may be associated with intrauterine growth restriction and microsomia (Van Assche et al, Br Med Bull, 2001)

Contd…

29

Module I: Introduction to Diabetes in Pregnancy

PATHOGENESIS OF MACROSOMIA

The Pedersen - Freinkel Hypothesis

Freinkel N. Diabetes, 1980

Slide 44

PATHOGENESIS OF MACROSOMIA

The Pedersen Hypothesis

Maternal hyperglycemia leads to excess exposure of the

fetus to maternal glucose, fetal hyperinsulinemia, and excess

growth

This concept was further refined by Freinkel, who added a

potential role of other nutrients (“mixed nutrients”) in fetal

overgrowth

Slide 43

Notes:

Notes:

OTHER METABOLIC PROBLEMS

IN THE NEONATE

Hypoglycemia

This occurs due to abrupt cessation of delivery of maternal

glucose to a neonate whose insulin levels are high following

exposure to chronic maternal hyperglycemia during pregnancy

Slide 45

Note: The Pedersen hypothesis, later modified by Freinkel, suggests that macrosomia results from excess supply of glucose and other nutrients (“mixed nutrients”) to the fetus, and consequent hypersecretion of insulin by the fetal pancreas. (Freinkel N, Diabetes, 1980)

NEONATAL HYPOGLYCEMIA IS INVERSELY RELATED TO

MATERNAL HYPERGLYCEMIA AT DELIVERY

Therefore good control of maternal diabetes can prevent neonatal hypoglycemia

Jovanovic L, Peterson CM. Am J Med, 1983

Slide 46

Note: In any form of diabetes in

pregnancy, the higher the maternal

plasma glucose levels at delivery, the

greater the risk of hypoglycemia in the

neonate. (Jovanovic L, Peterson CM. Am J

Med, 1983)

IMPAIRED FETAL LUNG MATURATION

Respiratory Distress Syndrome

• In a diabetic pregnancy, lung maturation is delayed due to reduced surfactant production secondary to hyperglycemia and hyperinsulinemia

• Poorly controlled diabetes in pregnancy is an important risk factor for RDS

Slide 48

OTHER METABOLIC PROBLEMS IN THE NEONATE

• Polycythemia occurs due chronic intrauterine hypoxemia and placental insufficiency secondary to poor glycemic control

• As these excess RBCs break down, hyperbilirubinemia occurs days to weeks after birth

• The exact mechanism of hypocalcemia is unknown but may be related to functional hypoparathyroidism (Tsang J et al, J Pediatr, 1975)

Slide 47

Notes:

Notes:

30

Certificate Course in Gestational Diabetes Mellitus

29

Module I: Introduction to Diabetes in Pregnancy

PATHOGENESIS OF MACROSOMIA

The Pedersen - Freinkel Hypothesis

Freinkel N. Diabetes, 1980

Slide 44

PATHOGENESIS OF MACROSOMIA

The Pedersen Hypothesis

Maternal hyperglycemia leads to excess exposure of the

fetus to maternal glucose, fetal hyperinsulinemia, and excess

growth

This concept was further refined by Freinkel, who added a

potential role of other nutrients (“mixed nutrients”) in fetal

overgrowth

Slide 43

Notes:

Notes:

OTHER METABOLIC PROBLEMS

IN THE NEONATE

Hypoglycemia

This occurs due to abrupt cessation of delivery of maternal

glucose to a neonate whose insulin levels are high following

exposure to chronic maternal hyperglycemia during pregnancy

Slide 45

Note: The Pedersen hypothesis, later modified by Freinkel, suggests that macrosomia results from excess supply of glucose and other nutrients (“mixed nutrients”) to the fetus, and consequent hypersecretion of insulin by the fetal pancreas. (Freinkel N, Diabetes, 1980)

NEONATAL HYPOGLYCEMIA IS INVERSELY RELATED TO

MATERNAL HYPERGLYCEMIA AT DELIVERY

Therefore good control of maternal diabetes can prevent neonatal hypoglycemia

Jovanovic L, Peterson CM. Am J Med, 1983

Slide 46

Note: In any form of diabetes in

pregnancy, the higher the maternal

plasma glucose levels at delivery, the

greater the risk of hypoglycemia in the

neonate. (Jovanovic L, Peterson CM. Am J

Med, 1983)

IMPAIRED FETAL LUNG MATURATION

Respiratory Distress Syndrome

• In a diabetic pregnancy, lung maturation is delayed due to reduced surfactant production secondary to hyperglycemia and hyperinsulinemia

• Poorly controlled diabetes in pregnancy is an important risk factor for RDS

Slide 48

OTHER METABOLIC PROBLEMS IN THE NEONATE

• Polycythemia occurs due chronic intrauterine hypoxemia and placental insufficiency secondary to poor glycemic control

• As these excess RBCs break down, hyperbilirubinemia occurs days to weeks after birth

• The exact mechanism of hypocalcemia is unknown but may be related to functional hypoparathyroidism (Tsang J et al, J Pediatr, 1975)

Slide 47

Notes:

Notes:

30

Certificate Course in Gestational Diabetes Mellitus

31

Module I: Introduction to Diabetes in Pregnancy

STILLBIRTHS

• Stillbirth rate in GDM is greater than that of the general population

• Majority occur even in the absence of congenital malformations

• Depends on the severity of diabetes and adequacy of metabolic control

• Rate of stillbirth is equal to that in the general population if mean blood glucose levels can be kept below 105-110 mg/dl

• Mainly related to excess fetal growth, consequent to hyperglycemia and hyperinsulinemia (Pettitt et al, Diabetes Care, 1980)

• May be due to osmotically induced edema of chorionic villi which decreases O

2 transport and leads to hypoxia and fetal acidemia

• However, fetal growth restriction can also contribute to stillbirths

Slide 49

Good control of glucose levels in the mother can significantly

reduce adverse pregnancy outcomes in GDM

This is one of the cornerstones of modern GDM management

Slide 50

GDM AND RISK OF FUTURE DIABETES IN THE OFFSPRING

Infants of mothers who had diabetes during pregnancy have

a higher risk of developing obesity, metabolic syndrome and

IGT/ type 2 diabetes in the future

Dabelea D, Diabetes Care, 2007

Offspring of women with GDM are at 4 to 8 times higher risk of

developing type 2 diabetes

Clausen TD, Diabetes Care, 2008

Contd…

Slide 51

Notes:

Notes:

Notes:

GDM AND RISK OF FUTURE DIABETES

IN THE OFFSPRING

Prevalence of type 2 diabetes, by mother’s diabetes during and after pregnancy in Pima Indians aged 5–34 years. , Offspring of nondiabetic mothers; , offspring of pre-diabetic mothers; offspring of diabetic mothers

Dabelea D, Pettitt DJ, J Pediatr Endocrinol Metab, 2001

Slide 52

Note: The Figure shows the prevalence of

type 2 diabetes by age-group in offspring of

diabetic (women who had diabetes before or

during pregnancy), pre-diabetic (those who

developed diabetes after pregnancy), and

nondiabetic mothers. By age 5–9 and 10–14

years, diabetes was present almost exclusively

among the offspring of diabetic women. In all

age-groups, there was significantly more

diabetes in the offspring of diabetic women

than in those of pre-diabetic and nondiabetic

women. There were much smaller differences

in diabetes prevalence between offspring of

pre-diabetic and nondiabetic women.

(Dabelea D, Pettitt DJ. Pediatr Endocrinol

Metab, 2001)

GDM AND RISK OF METABOLIC SYNDROME

IN THE OFFSPRING

Moore TR. Am J Obstetr Gynecol, 2010

Slide 53

IMPLICATIONS TO THE MOTHER

Pre - Eclampsia

• Diabetic pregnancy is associated with a higher rate of hypertensive complications than normal pregnancy

• Risk of pre-eclampsia is increased in GDM (15%-20% vs. 5%-7% in non-GDM)

• This is due to a combination of insulin resistance, genetic factors, age and BMI

Sibai BM, Caritis S, Hauth J et al. Am J Obstet Gynecol , 2000

Slide 54

Note: Adult health outcomes and exposure

to maternal diabetes. The risk of developing

one or other of the components of metabolic

syndrome in adulthood is higher in infants

exposed to maternal diabetes in utero. Even

the presence of risk factor for GDM (without

overt hyperglycemia) confers excess risk.

(Moore TR. Am J Obstetr Gynecol, 2010)

Certificate Course in Gestational Diabetes Mellitus

32

Notes:

31

Module I: Introduction to Diabetes in Pregnancy

STILLBIRTHS

• Stillbirth rate in GDM is greater than that of the general population

• Majority occur even in the absence of congenital malformations

• Depends on the severity of diabetes and adequacy of metabolic control

• Rate of stillbirth is equal to that in the general population if mean blood glucose levels can be kept below 105-110 mg/dl

• Mainly related to excess fetal growth, consequent to hyperglycemia and hyperinsulinemia (Pettitt et al, Diabetes Care, 1980)

• May be due to osmotically induced edema of chorionic villi which decreases O

2 transport and leads to hypoxia and fetal acidemia

• However, fetal growth restriction can also contribute to stillbirths

Slide 49

Good control of glucose levels in the mother can significantly

reduce adverse pregnancy outcomes in GDM

This is one of the cornerstones of modern GDM management

Slide 50

GDM AND RISK OF FUTURE DIABETES IN THE OFFSPRING

Infants of mothers who had diabetes during pregnancy have

a higher risk of developing obesity, metabolic syndrome and

IGT/ type 2 diabetes in the future

Dabelea D, Diabetes Care, 2007

Offspring of women with GDM are at 4 to 8 times higher risk of

developing type 2 diabetes

Clausen TD, Diabetes Care, 2008

Contd…

Slide 51

Notes:

Notes:

Notes:

GDM AND RISK OF FUTURE DIABETES

IN THE OFFSPRING

Prevalence of type 2 diabetes, by mother’s diabetes during and after pregnancy in Pima Indians aged 5–34 years. , Offspring of nondiabetic mothers; , offspring of pre-diabetic mothers; offspring of diabetic mothers

Dabelea D, Pettitt DJ, J Pediatr Endocrinol Metab, 2001

Slide 52

Note: The Figure shows the prevalence of

type 2 diabetes by age-group in offspring of

diabetic (women who had diabetes before or

during pregnancy), pre-diabetic (those who

developed diabetes after pregnancy), and

nondiabetic mothers. By age 5–9 and 10–14

years, diabetes was present almost exclusively

among the offspring of diabetic women. In all

age-groups, there was significantly more

diabetes in the offspring of diabetic women

than in those of pre-diabetic and nondiabetic

women. There were much smaller differences

in diabetes prevalence between offspring of

pre-diabetic and nondiabetic women.

(Dabelea D, Pettitt DJ. Pediatr Endocrinol

Metab, 2001)

GDM AND RISK OF METABOLIC SYNDROME

IN THE OFFSPRING

Moore TR. Am J Obstetr Gynecol, 2010

Slide 53

IMPLICATIONS TO THE MOTHER

Pre - Eclampsia

• Diabetic pregnancy is associated with a higher rate of hypertensive complications than normal pregnancy

• Risk of pre-eclampsia is increased in GDM (15%-20% vs. 5%-7% in non-GDM)

• This is due to a combination of insulin resistance, genetic factors, age and BMI

Sibai BM, Caritis S, Hauth J et al. Am J Obstet Gynecol , 2000

Slide 54

Note: Adult health outcomes and exposure

to maternal diabetes. The risk of developing

one or other of the components of metabolic

syndrome in adulthood is higher in infants

exposed to maternal diabetes in utero. Even

the presence of risk factor for GDM (without

overt hyperglycemia) confers excess risk.

(Moore TR. Am J Obstetr Gynecol, 2010)

Certificate Course in Gestational Diabetes Mellitus

32

Notes:

Module I: Introduction to Diabetes in Pregnancy

33

IMPLICATIONS TO THE MOTHER

Pre - Eclampsia

The rate of pre-eclampsia depends on the severity of GDMYogev Y, Am J Obstetr Gynecol, 2004

Slide 55

IMPLICATIONS TO THE MOTHER

Risk of Future Diabetes

• Following delivery, diabetes persists in 5% to 10% of women diagnosed to have GDM

• 35% to 60% of women with GDM will develop type 2 diabetes within 10 years

• Conversion to diabetes occurs more frequently, and faster, in high risk ethnic groups (such as Asian Indians)

Tovar A et al. Prev Chronic Dis, 2011

Slide 56

Note: The figure shows the rate of pre-

eclampsia in relation to the severity of GDM,

as assessed by fasting plasma glucose. Higher

the FPG, more the prevalence of PET. (Yogev Y.

Am J Obstetr Gynecol, 2004)

Notes:

Notes:

EPIDEMIOLOGY OF GDM

Slide 57

SAFES 2014-16

34

Certificate Course in Gestational Diabetes Mellitus

EPIDEMIOLOGY OF GDM

Global Scenario

• Prevalence of GDM varies according to the population studied, test used, timing of testing and criteria used

• Global prevalence rates vary from 1% to >15%

• The prevalence rate of GDM in a population is proportional to that of diabetes and IGT in that population (King, Diabetes Care, 1998)

Slide 58

Notes:

EPIDEMIOLOGY OF GDM

Indian Scenario

• Prevalence of GDM is steadily rising in India

• The rates increased from 2% in 1982 (Agarwal and Gupta) to 7.6% in 1991 (Narendra) and 16.55% in 2002 (Seshiah)

• In a multicentric study in India, the highest prevalence of GDM was found in Tamil Nadu and the lowest in Kashmir (Seshiah et al, 2004)

Contd…

Slide 59

EPIDEMIOLOGY OF GDM

Indian Scenario

GDM is more prevalent in the urban areas and among older and more

obese womenSeshiah et al, J Assoc Physicians India, 2008

Slide 60

Notes:

Note: A study conducted in 11,256 pregnant

women in Tamil Nadu showed that the urban

areas had the highest prevalence rates of

GDM compared to semi-urban and rural

areas. The prevalence of GDM increased with

increasing age and BMI of the mother.

(Seshiah et al, J Assoc Physicians India, 2008)

Module I: Introduction to Diabetes in Pregnancy

33

IMPLICATIONS TO THE MOTHER

Pre - Eclampsia

The rate of pre-eclampsia depends on the severity of GDMYogev Y, Am J Obstetr Gynecol, 2004

Slide 55

IMPLICATIONS TO THE MOTHER

Risk of Future Diabetes

• Following delivery, diabetes persists in 5% to 10% of women diagnosed to have GDM

• 35% to 60% of women with GDM will develop type 2 diabetes within 10 years

• Conversion to diabetes occurs more frequently, and faster, in high risk ethnic groups (such as Asian Indians)

Tovar A et al. Prev Chronic Dis, 2011

Slide 56

Note: The figure shows the rate of pre-

eclampsia in relation to the severity of GDM,

as assessed by fasting plasma glucose. Higher

the FPG, more the prevalence of PET. (Yogev Y.

Am J Obstetr Gynecol, 2004)

Notes:

Notes:

EPIDEMIOLOGY OF GDM

Slide 57

SAFES 2014-16

34

Certificate Course in Gestational Diabetes Mellitus

EPIDEMIOLOGY OF GDM

Global Scenario

• Prevalence of GDM varies according to the population studied, test used, timing of testing and criteria used

• Global prevalence rates vary from 1% to >15%

• The prevalence rate of GDM in a population is proportional to that of diabetes and IGT in that population (King, Diabetes Care, 1998)

Slide 58

Notes:

EPIDEMIOLOGY OF GDM

Indian Scenario

• Prevalence of GDM is steadily rising in India

• The rates increased from 2% in 1982 (Agarwal and Gupta) to 7.6% in 1991 (Narendra) and 16.55% in 2002 (Seshiah)

• In a multicentric study in India, the highest prevalence of GDM was found in Tamil Nadu and the lowest in Kashmir (Seshiah et al, 2004)

Contd…

Slide 59

EPIDEMIOLOGY OF GDM

Indian Scenario

GDM is more prevalent in the urban areas and among older and more

obese womenSeshiah et al, J Assoc Physicians India, 2008

Slide 60

Notes:

Note: A study conducted in 11,256 pregnant

women in Tamil Nadu showed that the urban

areas had the highest prevalence rates of

GDM compared to semi-urban and rural

areas. The prevalence of GDM increased with

increasing age and BMI of the mother.

(Seshiah et al, J Assoc Physicians India, 2008)

35

Module I: Introduction to Diabetes in Pregnancy

PUBLIC HEALTH IMPORTANCE OF GDM

• GDM has public health importance far beyond its immediate effects on the mother and child

• 35% to 60% of women with GDM will develop type 2 diabetes within 10 years; therefore, GDM is a major driver of the type 2 diabetes epidemic

• Infants of women with GDM have a higher prevalence of overweight or obesity as young children and adolescents, and a higher risk of developing type 2 diabetes later in life

Proper management and follow-up of women with GDM and their offspring has the potential to prevent diabetes in two generations

Slide 61

TAKE - HOME MESSAGES

• Pregnancy is a diabetogenic state

• GDM results when the beta cell is unable to adapt to the diabetogenic milieu of pregnancy

• The prevalence of GDM is high in India

• Diabetes in pregnancy is associated with serious consequences to the baby as well as the mother, if early detection and appropriate treatment are not offered

Slide 62

Notes:

Notes:

Notes:

Certificate Course in Gestational Diabetes Mellitus

36

Primer to Module II

PRIMER TO MODULE II

Slide 63

Slide 64

MODULE II

Screening and Diagnosis of GDM

• Screening for GDM

• Diagnosis of GDM

• Pre-existing diabetes and pregnancy

Notes:

Notes:

SAFES 2014-16

35

Module I: Introduction to Diabetes in Pregnancy

PUBLIC HEALTH IMPORTANCE OF GDM

• GDM has public health importance far beyond its immediate effects on the mother and child

• 35% to 60% of women with GDM will develop type 2 diabetes within 10 years; therefore, GDM is a major driver of the type 2 diabetes epidemic

• Infants of women with GDM have a higher prevalence of overweight or obesity as young children and adolescents, and a higher risk of developing type 2 diabetes later in life

Proper management and follow-up of women with GDM and their offspring has the potential to prevent diabetes in two generations

Slide 61

TAKE - HOME MESSAGES

• Pregnancy is a diabetogenic state

• GDM results when the beta cell is unable to adapt to the diabetogenic milieu of pregnancy

• The prevalence of GDM is high in India

• Diabetes in pregnancy is associated with serious consequences to the baby as well as the mother, if early detection and appropriate treatment are not offered

Slide 62

Notes:

Notes:

Notes:

Certificate Course in Gestational Diabetes Mellitus

36

Primer to Module II

PRIMER TO MODULE II

Slide 63

Slide 64

MODULE II

Screening and Diagnosis of GDM

• Screening for GDM

• Diagnosis of GDM

• Pre-existing diabetes and pregnancy

Notes:

Notes:

SAFES 2014-16

Notes:

Module I: Introduction to Diabetes in Pregnancy

Notes:

Module I: Introduction to Diabetes in Pregnancy