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Transcript of Diabetes Mellitus And Pregnancy BY Mohammed shereif MD of Internal Medicine Endocrine unit Faculty...
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Diabetes Mellitus And Pregnancy
BY
Mohammed shereif MD of Internal Medicine
Endocrine unit
Faculty of Medicine-Mansoura University
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☻ AGENDA: Review On Diabetes Mellitus.
Endocrinology Of Pregnancy.
Diabetes Mellitus And Pregnancy.
Complications of Diabetes on
pregnancy.
Management.
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Review On Diabetes Mellitus
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DIABETES MELLITUS: DEFINED
Diabetes is a group of metabolic diseases
characterized by hyperglycemia.
Hyperglycemia resulting from defects in insulin
secretion, insulin action, or both.
The chronic hyperglycemia of diabetes is associated
with long-term damage, dysfunction, and failure of
different organs, especially the eyes, kidneys, nerves,
heart, and blood vessels
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DIABETES CLASSIFICATION:
♣ Type 1 (IDDM).
♣ Type 2 (NIDDM).
♣ Gestational diabetes.
♣ Other specific types.
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Criteria for the diagnosis of diabetes mellitus:
Symptoms of diabetes and rondam plasma glucose ≥ 200 mg/dl (11.1 mmol/l).
OR
FPG ≥ 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hours.
OR
2-h plasma glucose ≥ 200mg/dl (11.1 mmol/l) during an OGTT.
OR
A1C ≥ 7%.
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Endocrinology Of Pregnancy
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The placenta produces larger quantities of more
hormones than any other human organ.
Placental Diabetogenic Hormones are:
Progesterone, Cortisol, GH
Human Placental Lactogen (HPL), Prolactin
Placental hormones affect glucose and lipid
metabolism to ensure that fetus has ample
supply of nutrients.
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Changes in maternal metabolism during normal pregnancy:
♣ Decreased fasting plasma glucose level.♣ Increased post prandial plasma glucose.♣ Increased plasma insulin level and IR.♣ ß- cell hypertrophy and hyperplasia.♣ Increased fat metabolism.♣ Increased ketone production.♣ Decreased circulating amino acids.♣ Decreased glucose production in the liver.♣ renal threshold for glucose glycosuria.
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Pregnancy Pathophysiology: Insulin resistance occurs because the hormonal changes
associated with pregnancy partially block the effects of insulin.
Maternal pancreatic beta cells increase insulin secretion almost three fold to compensate for increased insulin resistance.
If the mother’s pancreas is unable to produce sufficient insulin to overcome insulin resistance, maternal glucose levels increase and GDM occurs.
GDM may disappears after pregnancy because the hormonal changes that caused insulin resistance are no longer present.
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Diabetes Mellitus And Pregnancy
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Diabetes in Pregnancy: Types Gestational Diabetes Mellitus (GDM)
♣ Type A1: abnormal (OGTT) but normal blood glucose levels during fasting and 1-2 hours after meals.
♣ Type A2: abnormal (OGTT) with abnormal glucose levels during fasting and/or after meals.
Pregestational Diabetes Mellitus♣ Type 1: autoimmune process that destroys pancreatic
B cells.♣ Type 2 (“lifestyle diabetes”): acquired insulin
resistance related to obesity.
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Criterion White Classification
Gestational diabetes, insulin not required A1
Gestational diabetes, insulin required A2
Onset at age 20 years or older and duration of less than 10 years B
Onset at age 10-19 years or duration of 10-19 years C
Age of onset < 10 years of age D1
Duration >= 20 years D2
Calcification of vessels of the leg (macrovascular disease), formerly called Class E
D3
Benign retinopathy (microvascular disease) or Hypertension (not preeclampsia)
D4
Proliferating retinopathy R
Nephropathy F
Criteria for both classes R and F RF
Many pregnancy failures G
Evidence of arteriosclerotic heart disease H
Renal transplant T
Diabetes in Pregnancy:Diabetes in Pregnancy: ClassificationClassification
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Pregestational Diabetes: Types 1 and 2
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Gestational Diabetes Mellitus:“Any degree of glucose intolerance with onset
or first recognition during pregnancy.”♣ The definition applied whether insulin or only The definition applied whether insulin or only
diet modification is used for treatment of GDM.diet modification is used for treatment of GDM.♣ It does not exclude the possibility It does not exclude the possibility
that unrecognized glucose intolerance that unrecognized glucose intolerance
may have antedated or begun may have antedated or begun
concomitantly with the pregnancy.concomitantly with the pregnancy.
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Risk Risk AssessmentAssessment
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Risk factors for developing Risk factors for developing GDM:GDM:
A family history.A family history.
Gestation diabetes in a previous pregnancy.Gestation diabetes in a previous pregnancy.
Obesity and BMI > 30 kg/m2Obesity and BMI > 30 kg/m2
Older maternal age > 30 y.Older maternal age > 30 y.
Previous still birth or spontaneous miscarriage.Previous still birth or spontaneous miscarriage.
A previous delivery of a large baby ( > 9 bounds).A previous delivery of a large baby ( > 9 bounds).
Women of hispanic, or African American.Women of hispanic, or African American.
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Low risk for GDM:♣ Age less than 25 years. ♣ Normal weight before pregnancy (BMI less
than 25 kg/m2). ♣ Member of an ethnic group with a low
prevalence of GDM♣ No first degree relative with diabetes mellitus.♣ No history of abnormal glucose tolerance.♣ No history of poor obstetric outcome.
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Screening For GDM
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SelectiveUniversal
Obesity
Age Age 25 years 25 years
Familial diabetes
Poor obstetric outcome
Abnormal glucose metabolism
based on
Clinics in laboratory medicine, 21.1 March 2001, 173-192
Diabetes Care 23.1, ADA clinical practice recommendation 2000
High GDM prevalence ethnic groups
Performing GCT in all pregnant women
Screening StrategyScreening Strategy
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Whom to Screen for GDM ? Low Risk Group
♣ No screening required for GDM
Intermediate Risk Group♣ Screen around 24–28 weeks of gestation
High Risk Group♣ As soon as possible after conception♣ Must - before 24–28 weeks of gestation♣ Better do a full 3 hr OGTT for GDM♣ If negative screening in 2nd & 3rd trimester
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Screening strategies for GDM
☻The approach
One-step approach
Two-step approach
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☻One step approach:♣ Perform a diagnostic oral glucose
tolerance test (OGTT) without prior
plasma or serum glucose testing.
♣ Cost effective in high risk patients or
population.
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☻Two step approach:
Initial screening plasma or serum glucose 1h after
50gm oral glucose load.
Exceeding the Glucose threshold value or the GCT
Diagnostic OGTT
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♣ Two step approach glucose threshold
> 140 mg 80% of women with GDM
and the yield is further increased to 90%
by using a cutoff of > 130 mg/dl.
POSITIVE SCREEN DOES NOT
ESTABLISH THE DIAGNOSIS OF
GESTATIONAL DIABETES!!!
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50-g oral glucose challenge The screening test for GDM, may be performed
in the fasting or fed state. Sensitivity is improved if the test is performed in the fasting state.
A plasma value above 130 - 140 mg/dl one hour after is commonly used as a threshold for performing a 3-hour OGTT.
If initial screening is negative, repeat testing is performed at 24 to 28 weeks.
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Diagnosis Of GDM
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3 hour Oral glucose tolerance testPrerequisites:
♣ Normal diet for 3 days before the test.
♣ At least 10 hours fast.
♣ Test is done in the morning at rest.
Giving 75 gm (100 gm by other authors) glucose in 250 ml water orally.
2 or more values greater than or equal to the following cutoffs is diagnostic of GDM.
single abnormal value indicates CHO intolerance.
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♣ For ADA criteria 2 or more values from either 100 or 75 g OGTT must be met or exceeded to make the diagnosis of GDM
♣ For WHO criteria, one of the 2 values must be met or exceeded to make the diagnosis of GDM
OGTT GTT 100gr GTT 75gr
Criteria ADA ADA
Sample Plasma
(mg/dl)
Plasma
(mg/dl)
Fasting 95 95
1 h 180 180
2 h 155 155
3 h 140 ---
Diagnostic Criteria for GDMDiagnostic Criteria for GDM
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Complications of
Diabetes on pregnancy
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NEONATAL COMPLICATIONS:
Congenital anomalies.
Premature delivery.
Perinatal asphyxia.
Macrosomia and Shoulder Dystocia.
Respiratory distress syndrome.
Hyperbilirubinemia.
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Cardiomyopathy.
Polycythemia and hyperviscosity syndrome.
Metabolic complications.
Late effects on the offspring:
Increased risk of IGT.
Future risk of T2DM.
Risk of Obesity.
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Macrosomic Newborn (4.2kg)
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Shoulder Dystocia
Erb’s palsy
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Maternal COMPLICATIONS:♣ Difficult diabetic control (Ketoacidosis).
♣ Repeated infections during pregnancy and
puerperium.
♣ PET and eclampsia: 15-20%.
♣ Operative and difficult deliveries: increased CS
rate.
♣ Postpartum hemorrhage.
♣ Increase incidence of diabetic complications:
nephropathy, neuropathy and retinopathy.
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Management
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Prepregnancy Evaluation Of Diabetic Women
Complete history and physical examination.
Multidisciplinary team including obstetricians,
endocrinologists, dieticians, & midwives optimize
outcome.
To achieve normoglycemia as far as possible:
♣ FBS < 95 mg/dL.
♣ 1h PP < 140 mg/dL.
♣ 2h PP < 120 mg/dL.
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Monitoring:♣ SMBG intermittent office monitoring.
♣ For women treated by insulin 1h post -
prandial monitoring is superior to pre-prandial
monitoring.
♣ Urine glucose not useful in GDM.
♣ Urine ketone be useful in detecting insufficient caloric or carbohydrate intake in women treated with calorie restriction.
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Target Blood Glucose Values
Our blood glucose goals in pregnant diabetic
women are:
♣ ACOG:♥ Fasting glucose concentrations ≤ 95 mg/dL (5.3
mmol/L).
♥ Preprandial glucose concentrations no higher than
100 mg/dL (5.6 mmol/L).
♥ One-hour postprandial glucose concentrations no
higher than 140 mg/dL (7.8 mmol/L).
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♥ Two-hour postprandial glucose concentrations no
higher than 120 mg/dL (6.7 mmol/L).
♥ Mean capillary glucose 100 mg/dL (5.6 mmol/L)
and glycosylated A1C ≤ 6 percent (ACOG, 2005).
♣ ADA:
♥ Preprandial glucose concentrations 80 to 110 mg/dL
(4.4 to 6.1 mmol/L).
♥ Two-hour postprandial glucose concentrations no
higher than 155 mg/dL (8.6 mmol/L) (ADA, 2004).
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Nutritional counseling♣ Registered dietitian.
♣ Individualization of medical nutrition
therapy (MNT).
♣ Adequate calories and nutrients to meet
the needs of pregnancy.
♣ Non caloric sweeteners.
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Nutritional RecommendationsDistribution of total calories is:
♣ 35-45 % carbohydrates.♣ 20-25 % protein.♣ 35-40 % fat.
Most programs suggest three meals and three snacks, however, in overweight and obese women the snacks are often eliminated.
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Exercise !Moderate regular exercise
such as: walking, cycling
or swimming are excellent
forms of exercise for
pregnant women. Keeping
well-hydrated and
well-nourished is essential
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Medical Therapy: If normoglycemia cannot be maintained by
medical nutritional therapy, then anti-
hyperglycemic agents should be initiated.
Insulin.
Oral anti-hyperglycemic agents.
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Insulin: Insulin therapy is recommended when MNT fails to
maintain self monitored glucose at the following level (ACOG&ADA):♠ FBG < 95 mg/dl or
♠ 1h PPPG < 130-140mg/dl or
♠ 2h PPPG < 120 mg/dl.
Use of insulin preparations of low antigenicity will minimize the transplacental transport of insulin antibodies: human insulin is the least immunogenic of
the commercially available preparations.
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Regular insulin, which is often used in
pregnancy for the treatment of diabetes has
some drawbacks:
It starts its action from 30 to 60 min after
subcutaneous injection and it peaks too late (2-4 h
after injection) to be very effective in postprandial
control.
In addition, it lasts too long (duration of 6-8 h), with
an increased risk of postprandial hypoglycemia.
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Insulin molecules clump in hexamers that must
be broken up to dimers and monomers before
absorption, so delaying their effectiveness.
Therefore, in the last few years
insulin analogues started to be used
to optimize glucose control during
pregnancy.
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The New Insulin Analogues
Insulin LisproInsulin Lispro
Insulin AspartInsulin Aspart
Insulin GlulisineInsulin Glulisine
Insulin GlargineInsulin Glargine
Insulin DetemirInsulin Detemir
Rapidly Acting Long acting
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Insulin Lispro: There are various safety issues to consider:
Immunogenicity,Teratogenicity, Embryotoxicity, and Retinopathy.
The studies reported to date suggest that insulin lispro may be considered a treatment option in patients with GDM.
Insulin Aspart: Aspart insulin is now approved for use in
pregnancy and offers a valuable treatment option.
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Insulin Glulisine: At present no reports on glulisine use in
pregnancy are available.
Insulin Detemir: At present there are data on the use of detemir
in pregnancy with no difference from NPH
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Insulin Glargine:
At present the use of insulin glargine in
pregnancy is approved:
♣ Concerns have been raised about the high affinity of
glargine for the IGF-1 receptor and the potential
sequelae of macrosomia.
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Insulin TitrationThe starting insulin dose can be calculated
on the basis of the patient's weight
♣ The average insulin requirement in pregnant women
is 0.7 units/kg in the first trimester, often increasing to
0.8 U/kg for weeks 13 to 28, 0.9 U/kg for weeks 29 to
34, and 1.0 U/kg for weeks 35 to term.
♣ In a pregnant diabetic patient the rationale for insulin
therapy is based on mimicking the physiology of
insulin secretion.
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♣ The basal insulin is supplied by the administration of
NPH, lente, ultralente insulin at bedtime or both before
breakfast and at bedtime.
♣ The meal-related (glucose excursion) insulin includes
the use of insulin lispro or aspart before meals (0-15
min) or regular insulin before meals (30-45 min).
♣ This method characterized the intensified therapy
(multiple injections daily) versus conventional therapy
(one or two injection daily).
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Oral Anti Diabetic Drugs
The use of Acarbose, Thiazolidinediones,
Glinides and Glucagon-like peptide 1
agonists is contraindicated during
pregnancy
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Sulfonylureas are currently the only
drugs to be studied in GDM women in
randomized controlled trials.
Most data regarding oral antidiabetic
drug safety in pregnancy are
regarding Glyburide.
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Metformin Metformin is classified as a category B drug, which
implies that there is no evidence of animal or fetal
toxicity or teratogenicity.
Metformin does not stimulate insulin secretion and
does not cause hypoglycemia.
The concentration of metformin in breast milk is
generally low and mean infant exposure to the drug is
clearly below the 10% level. Therefore, use of
metformin by breast-feeding mothers is safe.
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In PCOS, use of Metformin is associated
with a tenfold reduction in gestational
diabetes (from 31 to 3%) and it is safely
associated with spontaneous abortion
reduction (from 73 to 10%).
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Although , most current studies demonstrate
that oral hypoglycemic agents, such as
Glyburide and Metformin, are safe to use in
pregnancy with maternal and perinatal
outcomes similar to insulin treatment.
But there is a need for a randomized controlled
trial with long-term follow up of both mothers
and children.
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Long-term therapeutic
considerations♫ At least six weeks after delivery, all women with
previous GDM should undergo an oral glucose tolerance test using a two-hour 75 gram oral glucose tolerance test.
♫ Reclassification of maternal glycemic status should be performed at least 6 weeks after delivery and according to the guidelines of the “Report of the Expert Comitte on the Diagnosis and Classification of DM”
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Criteria for the diagnosis of diabetes mellitus
Normoglycemia IFG and IGT Diabetes mellitus
FPG <100 mg/dl FPG 100 mg/dl and <126 mg/dl
(IFG) FPG > 126 mg/dl
2-h PG <140 mg/dl 2-h PG 140
mg/dl and <200 mg/dl (IGT)
2-h PG > 200 mg/dl
— —
Symptoms of DM and casual plasma glucose concentration > 200 mg/dl
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♣ Women with gestational diabetes rarely require
insulin in the postpartum period and
approximately 15% of those remain glucose
intolerant or demonstrate overt diabetes in the
postpartum state.
♣ If glucose level are normal post-partum,
reassessment of glycemia should be undertaken
at a minimum of 3-years intervals.
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♣ Women with IFG or IGT in the postpartum
period should be tested for DM annually.
These patients should receive intensive MNT
and should be placed on an exercise program.
♣ The patients should be educated to seek
medical attention if they develops symptoms
suggestive of hyperglycemia.
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Summary
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Diabetes in pregnancy may be gestational diabetes or
pregestational diabetes.
pregnancy is diabetogenic as it converts latent to
overt diabetes.
Adequate blood glucose levels during pregnancy,
reduces morbidity of both mother and child
Diet represents the mainstay for glycemic control.
Insulin aspart and lispro has been approved during
pregnancy.
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Insulin glargine,and detemir do not show any contraindications during pregnancy.
Insulin glulisine has no data regarding their use in pregnancy.
Glyburide and Metformin, are safe to use in pregnancy with maternal and perinatal outcomes similar to insulin treatment.
The routine use of oral antidiabetic drugs during pregnancy is not recommended because of the necessity of randomized clinical trials with long-term follow-up for both mother and child.
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