2011 BEST OF IDF DIABETES AND PREGNANCY

Mesbah Sayed Kamel MD

AGENDA Gestational diabetes mellitus(GDM). Hyperglycemia and Adverse Pregnancy Outcomes

(HAPO) study. Shared Care of Diabetes with pregnancy. Pre-Conception Counseling to Women with

Diabetes. Diabetes in pregnancy: Future risks for mothers

and offspring. The practice of fasting among pregnant women

with diabetes during Ramadan. Oral Ant Diabetic Drugs (ADD) in Pregnancy and

Lactation. Fetal and neonatal Safety .

Challenges in gestational diabetes mellitus

Gestational diabetes (GDM) is common and affects approximately 1 in 25 pregnancies globally.

Undiagnosed or inadequately treated GDM can lead to larger than normal babies and higher rates of problems with the pregnancy and increased infant deaths and fetal abnormalities.

Women with GDM are at increased risk of developing diabetes and the offspring of GDM pregnancies are at increased risk of obesity and type 2 diabetes in later life.

Colagiuri Abst.108

Cytokine Profile and Markers Oxidative Stress in Women with GDM

Women with GDM have more risk to have increased CVD markers, expressed at higher levels of TNF-α, LPO and lower levels of catalase and SOD.

This unfavorable cytokine profile and increased

oxidative stress, which remains in the postpartum period, high serum levels of CRP, interleukin 6, HOMA-IR and LDL-C i.e a permanent state of metabolic dysfunction would make them more likely to develop DM and CVD in the future.

(B. Edalat etal., -Diosdado etal., Abstract: P-1365)

Screening for GDM

Predictor markers for GDM

Early pregnancy low βhCG is associated with the GDM and, secretory defect and insulin resistance.(R. Helal etal., Abstract: D-0655)

Serum Apo C-III(one of apolipoprotein synthesized in the liver and is markedly secreted in insulin-

resistant state) levels in GCT positive subjects and patients with GDM found to be higher than in

GCT negative subjects and non-pregnant women.

(T. Hiyoshi etal. Abstract: D-0656)

Screening for GDM

A woman may NOT need screening for GDM if she meets ALL of the following criteria:

less than 25 years old not a member of a racial or ethnic group

with a high prevalence of diabetes (eg, Hispanic, African, Native American, South or East Asian, or Pacific Islands ancestry)

a body mass index (BMI) 25 no history of abnormal glucose tolerance no previous history of adverse pregnancy

outcomes usually associated with GDM no known diabetes in first-degree relative

Hyperglycemia & Adverse Pregnancy Outcome (HAPO) Study

The objective of this study was to clarify associations of levels of maternal glucose lower than those diagnostic of diabetes with perinatal outcome.

This was accomplished by performing a 75-g

oral glucose tolerance test (OGTT) on a heterogeneous, multinational, multicultural, ethnically diverse cohort of >25,000 women in the third trimester of gestation.

(B. Metzger,Abstract 173)

HAPO study, revealed three principal findings

1-Strong associations exist between maternal glucose levels (fasting, 1-hour and 2-hour) during pregnancy and pre-eclampsia.

2-There are strong and continuous associations between maternal plasma glucose levels, increased birth weight and cord-blood serum C-peptide levels with no apparent thresholds.

3-Glucose levels during pregnancy are associated with primary caesarean section, premature delivery, birth injury (such as shoulder dystocia), intensive neonatal care, and jaundice.

In response to this and other studies, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) has formulated new guidelines for screening and diagnosis of diabetes in pregnancy.

Key components of the IADPSG guidelines include the recommendation to screen high-risk women at the first encounter for pre-gestational diabetes, to screen universally at 24–28 weeks’ gestation, and to screen with use of the 75-g oral glucose tolerance test interpreting abnormal fasting, 1-h, and 2-h plasma glucose concentrations as individually sufficient for the diagnosis of gestational diabetes.

Opponents to the IADPSG recommendations will likely be those who favor risk-based screening in addition to those who endorse the 50-g glucose challenge test followed by the 100-g oral glucose tolerance test as a more cost-effective, familiar, and possibly, well-validated screening tool.

American College of Obestetric and Gynaecology Committee on Obstetric Practice Recommendations Number 504, September 2011

All pregnant women should be screened for GDM, whether by patient history, clinical risk factors, or a 50-g, 1-hour loading test to determine blood glucose levels.

The diagnosis of GDM can be made based on the result of the 100-g, 3-hour oral glucose tolerance test, for which there is evidence that treatment improves outcome. A positive diagnosis requires that two or more thresholds be met or exceeded.

Diagnosis of GDM based on the one-step screening and diagnosis test outlined in the International Association of Diabetes in Pregnancy Study Group guidelines is not recommended at this time because there is no evidence that diagnosis using these criteria leads to clinically significant improvements in maternal or newborn outcomes and it would lead to a significant increase in health care costs.

Shared care in management of diabetes with pregnancy

The effective management of pregnancies

complicated by diabetes is a shared responsibility—an equal partnership between health care professionals and a responsible woman, so as pregnancy outcomes for women with diabetes would be similar to the outcomes for women without diabetes.

Unfortunately this has not been realized with the risk of congenital malformations, stillbirths, and neonatal death remaining as high as 3–10 times that of the background population .

Proper approach to pregnancy management in diabetes can be successfully implemented even in low-to-middle income countries.

(X. Yang, Abstract: P-1724)

Pre-Conception Counseling to Women with Diabetes

Preconception counseling was associated with better glycemic control 3 months preconception.

Rates of preconception counseling in women with diabetes remain low despite the recognized importance of adequate preparation for pregnancy.(27%-37%).

A high proportion of pregnancies in women with diabetes, however, are known to be unplanned and this is a challenge to achieving high rates of attendance for preconception counseling.

Diabetes Care March 2010 vol. 33 no. 3 586-588

PRECONCEPTION CARE PROGRAM

To prevent excess spontaneous abortions and congenital malformations in infants of diabetic mothers, diabetes care and education must begin before conception. This is best accomplished by a multidisciplinary team that includes a diabetologist, internist, or family practice physician skilled in diabetes management; an obstetrician familiar with the management of high-risk pregnancies; diabetes educators, including a nurse, dietitian, and social worker; and other specialists, as deemed necessary.

(C. Rasmussen, Abstract: P-1738)

The model of diabetes preconception and early pregnancy health care is interactive. It includes four main elements:

1) patient education about the interaction of diabetes, pregnancy, and family planning;

2) education in diabetes self-management skills; 3) physician-directed medical care and laboratory

testing; 4) counseling by a mental health professional when

indicated to reduce stress and improve adherence to the diabetes treatment plan.

All four elements are important for patients to achieve the level of sustained glycemic control necessary to prevent excess congenital malformations and spontaneous abortions.

Diabetes in pregnancy: Future risks for mothers and offspring

1 - Evaluated evidence that maternal diabetes plays a role in offspring diabetes

2 - Consider potential mechanisms to explain the trans-generational risk.

3 - Consider directions to reduce the risk to mother and foetus.

Maternal contributions to subsequent metabolic disease in her offspring (P. Gluckman, Abstract: 389)

These relationships operate through epigenetic processes. They may also operate over more than one generation through direct and indirect forms of non-genomic (epigenetic) inheritance.

A variety of maternal circumstances can affect the offspring's metabolic phenotype including variation in maternal; nutrition across the range of intakes both in early and late pregnancy.

Evolved constraints on the transduction of environmental information from mother to fetus in humans resulting first born children to be at greater risk of obesity because of greater constraint on their intrauterine development.

Maternal obesity, gestational diabetes and premature weaning also have long term effects of disease risk through altering developmental trajectories.

The practice of fasting among pregnant women with diabetes during Ramadan

An improvement in overall blood sugar control

was noted in the fasting group with the HbA1c dropping more in fasting than in the non-fasting group.

Weight gain more in non-fasting than in the fasting pregnant ones

.

Patients with type 2 diabetes or gestational diabetes may safely fast in pregnancy if provided with adequate medical support.

Mahmood etal. , Abstract: P-1546).

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What does the evidence say about the fetal and neonatal safety about the use of Oral Ant Diabetic Drugs (ADD) in

Pregnancy and Lactation (Y. Masood etal., Abstract: D-0760)

Corniche hospital experience with Metformin

in pregnancy (Salih etal., Abstract: P-1542)

Results & Conclusions: • Glyburide and metformin are not teratogenic in

humans when used in clinically recommended doses.

• Glyburide may be used for treatment of gestational diabetes in some women.

• Metformin may be used safely for ovulation in women with PCOS.

• Metformin reduces the development of GDM, was not teratogenic and did not affect birth length, weight, growth motor or social development in children in first 18 months of life

•

Tolbutamide, Chloropropamide cross into the breast milk

• None of the glyburides pass in the breast milk samples.

• METFORMIN: Excreted in the breast milk at very low levels

• No differences in weight, height or motor-social development of the newborn or in the infants up to 3-6 months of age are reported.

Conclusions:

• There is evidence that certain oral hypoglycemic drugs might be safe in pregnancy, or at least, are significantly less dangerous to the developing fetus than poorly controlled diabetes.

• Metformin, Glyburide and Glypizide are compatible with breast feeding

• If the patient needs intervention but refuses insulin therapy, Patient must be made aware of potential or probable risks in Pregnancy of oral Hypoglycemic drugs

Thank you all For

Sparing your valuable time

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Patient listening