Diabetes mellitus during pregnancy

GYNE II

Objectives
Physiologic changes during pregnancy Types of Diabetes during pregnancy Pregestational diabetes
1. 2. 3. 4. Effects of pregnancy on diabetes Effects of diabetes on pregnancy Diagnosis Management

Gestational diabetes

Changes in glucose metabolism in pregnancy

Fasting hypoglycemia due to increased circulatory volume Progressive insulin resistance due to the release of anti-insulin hormones (hPL, cortisol, PRL and placental insulinase)

Increased insulin release (double the level of prepregnancy in the third trimester)

Normal glucose metabolism

Glucose enters bloodstream from food source Insulin aids in storage of glucose as fuel for cells Insulin resistance is defined as insensitivity of cells to insulin, therefore resulting in increased levels of insulin and glucose in the bloodstream

Metabolic changes in pregnancy

Caloric requirement for a pregnant woman is 300 kcal higher than the non-pregnant womans basal needs Placental hormones affect glucose and lipid metabolism to ensure that fetus has ample supply of nutrients

Metabolic changes in pregnancy

Lipid metabolism:
Increased lipolysis (preferential use of fat for fuel, in order to preserve glucose and protein)

Glucose metabolism:
Decreased insulin sensitivity Increased insulin resistance

Metabolic changes in pregnancy

Increased insulin resistance
Due to hormones secreted by the placenta that are diabetogenic:
Growth hormone Human placental lactogen Progesterone Corticotropin releasing hormone

Transient maternal hyperglycemia occurs after meals because of increased insulin resistance

Metabolic changes in pregnancy

Relative baseline hypoglycemia
Proliferation of pancreatic beta cells (insulin-secreting cells) leads to increased insulin secretion
Insulin levels are higher than in pregnant than nonpregnant women in fasting and postprandial states

Hypoglycemia between meals and at night because of continuous fetal draw

Blood glucose levels are 10-20% lower

Metabolic changes in pregnancy

Lipid metabolism
Increased serum triglyceride (300%) and cholesterol (50%) levels Spares glucose for fetus, since lipids do not cross the placenta Provides building blocks for increased steroid hormone synthesis

Preexisting diabetes mellitus (DM)

Size of the problem

Diabetes mellitus affects approximately 4 million women of childbearing age in the United States.
90% type II and 10% type I

 Either type 1 (iddm) or type 2 (niddm)

Type 1 occurs in younger age group and end organ complications is likely to be more. Hence they to have increased maternal and fetal risks
Type 2 usually occurs in obese patients and have less maternal and fetal risks compared to type 1. many will be using oral hypoglycemic drugs between pregnancies

Whites prognostic classification of DM with pregnancy

Class A1 Abnormal glucose tolerance test with normal fasting capillary (95 mg/dL) and postprandial (120 mg/dL) glucose levels Controlled with diet alone Class A2 Abnormal glucose tolerance test with abnormal fasting or postprandial glucose levels Treated with diet and insulin Background retinopathy

Class B Insulin-treated diabetic Onset over age 20 years Duration less than 10 years No vascular disease or retinopathy

Class C Insulin-treated diabetic Onset between ages 10 and 20 years Duration between 10 and 20 years Background retinopathy Class D Insulin-treated diabetic Onset under age 10 Duration more than 20 years

Class F Diabetic nephropathy Class H Cardiac disease Class R Proliferative retinopathy Class T Renal transplant

Diagnosis of Diabetes
Non Pregnant Fasting plasma BG >7.0mmol/l (126 mg/dL) Casual plasma BG >11.1mmol/l (200 mg/dL) Impaired Fasting Glucose FPG 6.1-7.0 mmol/l Impaired Glucose Tolerance normal FPG 2 h 75gOGTT test with BG 7.8 (140 mg/dL)-11.1 mmol/l (200 mg/dL)

Effects of pregnancy on DM
Increased insulin requirements (difficult control) More liability to fasting hypoglycemia More liable to DKA (type I) Nausea and vomiting may further complicate control Insulin requirements markedly drop after delivery

Effects of diabetes on the mother

First trimester: miscarriage Second trimester: polyhydramnios, hypertension Third trimester: polyhydramnios, hypertension, preeclampsia, preterm labor (spontaneous or induced) Delivery: increased risk of operative delivery and its resultant complications At all times, there is an increase risk of infection especially urinary tract, skin infections and monilial vulvovaginitis Deterioration of retinopathy, gastropathy, nephropathy and to a lesser extent; neuropathy

Effects of diabetes on the fetus

First trimester: miscarriage, malformation Second trimester: miscarriage (fetal demise) Third trimester: macrosomia (due to anabolic effect of insulin) growth retardation (in women with diabetic vasculopathy) fetal hypoxia or even fetal death

During delivery, the baby is liable to birth trauma and asphyxia and operative delivery.

Neonatal complications
After delivery, the infant of diabetic mother is liable to hypoglycemia (due to increased fetal insulin production secondary to increased glucose loads from the mother hypocalcemia Polycythemia jaundice (polycythemia) Hypomagnesemia Respiratory distress syndrome (decreased surfactant)

Congenital anomalies of infants of diabetic mothers.

Skeletal and central nervous system Caudal regression syndrome (200 times increased risk) Neural tube defects (2-10 times increased risk) Microcephaly Cardiac (4 times increased risk) Transposition of the great vessels Ventricular septal defects and Atrial septal defects Coarctation of the aorta defects or patent ductus arteriosus Cardiomegaly Renal (10 times increased risk) Hydronephrosis Renal agenesis Ureteral duplication Gastrointestinal (3-10 times increased risk) Duodenal atresia Anorectal atresia Small left colon syndrome Other Single umbilical artery

Management
Before pregnancy During pregnancy: Medical management During pregnancy: obstetric management Delivery Puerperium

Before pregnancy
Women with diabetic nephropathy (albuminuria, Creatinine >250 micromol/L or impaired creatinine clearance), cardiopathy (coronary artery disease), and gastropathy should avoid pregnancy Counsel women with proliferative retinopathy about possible deterioration Optimize glycemic control Type II to switch to Insulin if not on Insulin Stop ACE inhibitors Assess HBA1c (<6%)

Before pregnancy (2)

Assess fundus, urea and creatinine, protein in urine, ECG Do laser coagulation before pregnancy if proliferative retinopathy FOLIC ACID 5 MG BEFORE PREGNANCY Counsel about the need for tighter control, more frequent hypoglycemia, need for frequent maternal and fetal monitoring and increased rate of operative delivery and diabetes in the offspring (6% if mother has DM, 10% if father has DM)

 Glycosylated Hemoglobin A1C (Hgb A1C) level should be less than or equal to 6%
Levels between 5 and 6% are associated with fetal malformation rates comparable to those observed in normal pregnancies (2-3%) Goal of normal or near-normal glycosylated hemoglobin (Hgb A1C) level for at least 3 months prior to conception

Hgb A1C concentration near 10% is associated with fetal anomaly rate of 20-25%

During pregnancy
Diet: Three meals and three snacks 30-35 Kcal/Kg ideal body weight, 25 if obese No more than 10-12 Kg weight gain 50% of energy carbohydrates (unrefined), 30% fat and 20% proteins Review diet history to identify major areas of reduction of caloric intake Alert the patients and relatives about the possibility of hypoglycemia and measures to counteract

Insulin
Starting dose (0.6-0.8 U/Kg body weight in 1st trimester, 0.7-0.9 U/kg body weight in the 2nd trimester and 0.9-1.1 U/kg body weight in the 3rd trimester) Which types of insulin to give (short acting and intermediate [long acting stopped before pregnancy]) Dosage schemes twice daily or three times or four times. The more frequent, the tighter the control but increased inconvenience and less compliance

Glycemic targets Fasting: 60 90 mg/dL Preprandial: 80 95 mg/dL Postprandial: < 120 mg/dL Monitoring of glycemic control (clinically by symptoms of hyper and hypoglycemia, glucose profile weekly, HBA1c every 1-2 months) Glucose profile is home based assessment of glucose 7 times/day; fasting, 2 h after breakfast, before lunch, 2h after lunch, before dinner, 2 h after dinner and at midnight. This should be done weekly or at any time glucose control is suspected. Dose adjustment is undertaken according to the profile

Diabetic Ketoacidosis
5-10% of pregnant Type 1 pts Risk factors New onset DM Infection Steroids B mimetics Fetal mortality 10%

Management
Assess BG, ketones electrolytes Insulin 0.2-0.4U/Kg loading and 2-10U/h maintenance Begin 5% dextrose when BG is 14 mmol/l Potassium replacement Rehydration isotonic NaCl Replace Bicarb and phosphate as needed

Obstetric management
First trimester: aggressively manage nausea and vomiting Ultrasound (viability, nuchal fold thickness) Second trimester: Anomaly scan 16-20 w Fetal echo 24-26 w Third trimester Serial assessment of fetal growth Serial assessment of fetal wellbeing (start at 32 weeks) Start earlier at 28 w if growth restriction is suspected (women with vascular disease, nephropathy or hypertension) Women with poor control and IUGR are likely to have abnormal results of tests of fetal wellbeing

Delivery
If everything is OK, deliver at 38-40 weeks Route of delivery depends on fetal size, past obstetric performance and associated factors Keep a high threshold for CS Vaginal delivery should be conducted by a senior obstetrician trained to deal with accidents such as shoulder entrapment Women with proliferative retinopathy should not bear down If preterm termination is required and corticosteroids are given to accelerate lung maturation, an increased insulin requirement over the next 5 days should be anticipated, and the patients glucose levels must be closely monitored

Fluid and insulin management during and after delivery

Stop subcutaneous insulin once labor starts 5% dextrose at 100 ml/hour 50 unit short acting insulin/500 cc normal saline (2-3 units/hour) Measure capillary glucose hourly and serum glucose/4 h Maintain glucose <110 mg/dL Infuse Half the rate after delivery Give the prepregnancy dose once the patient is able to eat and drink normally

NEW BORN MANAGEMENT

SERIALLY ASSESS CAPILLARY GLUCOSE OF THE NEONATE ESPECIALLY IN THE FIRST 12 HOURS. REPLACE GLUCOSE IF THE GLUCOSE LEVEL IS LESS THAN 45 MG/DL IF THE HEMATOCRIT VALUE EXCEEDS 70, EXCHANGE TRANSFUSION SERIALLY MONITOR BILIRUBIN LEVEL

Gestational diabetes mellitus

Definition Glucose intolerance of variable severity first diagnosed in Pregnancy Prevalence 2-4% Risk Factors A family history of diabetes, especially in first degree relatives Prepregnancy weight more than 90 kg. Age >29 years A previous large baby (>9 pounds [4.1 kg]) History of abnormal glucose tolerance A previous unexplained perinatal loss or birth of a malformed child Polycystic ovary syndrome Glycosuria (repeated twice) at the first prenatal visit Current use of glucocorticoids

Effects on the mother and fetus

Increased liability to infections Preterm labor Polyhydramnios Preeclampsia Operative delivery All the effects of DM on the fetus except anomalies (why???) GDM is liable to recurrence 50-60% of women with GDM will develop type II DM later in life

GDM IS ASYMPTOMATIC. IT IS DETECTED BY SCREENING

Screening approaches Universal screening at 24-28w Screening high risk only Screening most women with few exception at 24-28w and earlier screening of women with risk factors

Criteria for avoiding laboratory screening for gestational diabetes

All criteria must be met for a patient to be considered low-risk and glucose testing avoided Age less than 25 years

Prepregnancy Body mass index of 25

No prior history of glucose intolerance (GDM, DM, IGT, or IFG) No prior history of obstetric outcomes associated with GDM (macrosomia, stillbirth, polyhydramnios, malformations) No known diabetes in a first-degree relative

Risk Factors
A family history of diabetes, especially in first degree relatives

pre-pregnancy weight more than 90 kg or more

Age >25 years A previous large baby (>9 pounds [4.1 kg]) History of abnormal glucose tolerance A previous unexplained perinatal loss or birth of a malformed child Polycystic ovary syndrome Glycosuria (repeated twice) at the first prenatal visit Current use of glucocorticoids

Criteria of the 1h, 50 g tolerance screening 1h >140 = GDM 1h <120 = no GDM 120-140 = glucose tolerance test (75 g or 100 g)

The 3-hour 100-g glucose tolerance test. * If two or more values meet or exceed these thresholds, the diagnosis of gestational diabetes is made.

Time Thresholds* Fasting 105 1-hour 190 2-hour 165 3-hour 145

Medical Management
Diet Insulin (indications) Oral hypoglycemic agents (promising) Peripartum management. Insulin can usually be withheld during labor delivery Infusion of normal saline is usually sufficient to maintain normoglycemia.

Obstetric Management
Similar to third trimester management of DM except: no need to deliver at 38 weeks if controlled diabetes especially on diet alone Antepartum fetal surveillance restricted to those with poor control, those on insulin or other associated obstetric factors that will necessitate fetal monitoring such as preeclampsia, hypertension or abnormal fetal movements

Do not forget Perform OGTT at 6 weeks to confirm disappearance of impaired glucose tolerance

Thank you