Diabetes in Pregnancy Introduction Introduction Affects up to 3% of all pregnancies 90% due to gestational diabetes Perinatal mortality around 2-5%

Pathophysiology Normal pregnancy: glucose homeostasisis affected by increased estrogen, progesterone &HPL which lead to B cell hyperplasia and increased insulin secretion. Lower maternal fasting glucose levels. Increased: glycogen deposition, fatty acids, triglycerides & ketones Decreased: circulating amino acids Maternal response is to increase protein catabolism and accelerate renal gluconeogenesis

Pathophysiology Normal pregnancy: lipids become an important fuel as pregnancy advances, fat storage increases. With the rise of HPL, lipolysis is stimulated in adipose tissue. The release of glycerol and fatty acids reduces both maternal glucose and amino acid utilization and sparing them for the fetus This action of HPL is responsible for the “diabetogenic state of pregnancy”along with increased cortisol. Estrogen and progesterone. Fetal glucose level is similar to the mothers by facilitated diffusion, insulin dose not cross the placenta. Persistant elevated levels of glucose will stimulate the pancreas resulting in β-cell hyperplasia and fetal hyperinsulinemia

Maternal classification and risk assessment Modified white classification of pregnant diabetic women class Onset age duration Vascular dis Insulin need A1Anyany00 A2anyAny0+ B>20<100+ C D<10>20++ FAnyAny++ RAnyAny++ TAnyAny++ HanyAny++ Gestational diabetes Pre-gestational diabetes

Effect of pre-existing diabetes on pregnancy Pre-eclampsia and eclampsia Pre-eclampsia and eclampsia Diabetic ketoacidosis Diabetic ketoacidosis Worsening pre-existing nephropathy Worsening pre-existing nephropathy Worsening pre-existing retinopathy Worsening pre-existing retinopathy Infection: genital > monilial Infection: genital > monilial Polyhydramnios/ oligohydramnios Polyhydramnios/ oligohydramnios Cesarean delivery Cesarean delivery Post partum hemorrhage Post partum hemorrhage mortlaity mortlaity

Fetal Morbidity and Mortality 1-miscarriage 1-miscarriage 2-teratogenecity, drug related 2-teratogenecity, drug related 3- Congenital Malformation 3- Congenital Malformation Caudal regression Caudal regression Neural tube defect Neural tube defect CVS CVS 4- Macrosomia / IUGR 4- Macrosomia / IUGR 5-Fetal Death 5-Fetal Death

Diabetes Mellitus and Gestational Diabetes Summery of Management Options 1- Pre-Pregnancy 1- Pre-Pregnancy  Explain general risks and management of diabetes in pregnancy  Evaluate any additional risks with appropriate specialist referral (e.g. renal, ophthalmologic)  Optimize blood glucose control  Discuss effective contraception until good glucose control (avoid estrogen containing-preparations with vascular disease)  Folate supplementation(4-5 mg daily) for at least 2 months before or during first trimester

B- prenatal 1- Detection of Diabetes in Pregnancy 1- Detection of Diabetes in Pregnancy 2- Treatment of the Insulin-Dependent Patient 2- Treatment of the Insulin-Dependent Patient 3- Fetal Surveillance 3- Fetal Surveillance 4- Management of Gestational Diabetes 4- Management of Gestational Diabetes

Pregnancy is diabetogenic 1. Occurrence of GDM 2. Unmasking latent DM 3. Worsening of existing DM 4. Shift of GTT upward 5. Need of more insulin in pregnancy 6. Need of less insulin after labour 7. High female to male ratio

Now we screen all gravid women Now we screen all gravid women At booking At booking At 28 weeks At 28 weeks High risk patients High risk patients Positive family history (mother, father, siblings) Positive family history (mother, father, siblings) Maternal obesity (BMI > 30 kg/m2, trunkal obesity) Maternal obesity (BMI > 30 kg/m2, trunkal obesity) Aged gravida Aged gravida Poor obstetric history Poor obstetric history Persistent glycosuria Persistent glycosuria Macrosomia Macrosomia Hydramnios Hydramnios Screening for DM

high risk patients should undergo glucose testing high risk patients should undergo glucose testing A fasting plasma glucose level >125mg/dL or a casual plasma glucose >200 mg/dL meets the threshold for the diagnosis of diabetes In the absence of this degree of hyperglycemia, evaluation for gestational diabetes mellitus in women with average or high-risk characteristics is by glucose tolerance test. Risk assessment

Methods of screening MethodSensitivitySpecificity Family history Random glucose Glucose load (WHO) Glycated Hb 50 % 40 % 79 % 40 % 66 % 90 % 83 % 90 %

Fasting and 2 hours postprandial venous plasma sugar during pregnancy. Border line indicates glucose tolerance test mg/dl mg/dl Diabetic >200 mg/ dl. >125 mg/ dl Not diabetic < 145mg/ dl. <100 mg/dl Result 2h postprandial Fasting

50-g oral glucose challenge The screening test for GDM, a 50-g oral glucose challenge, 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 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 mg/dl

3 hour Oral glucose tolerance test Prerequisites : - Normal diet for 3 days before the test. - No diuretics 10 days before. - 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 Criteria for glucose tolerance test: The maximum blood glucose values during pregnancy: - fasting 90 mg/ dl, - one hour 165 mg/dl, - 2 hours 145 mg/dl, - 3 hours 125 mg/dl. If any 2 or more of these values are elevated, the patient is considered to have an impaired glucose tolerance test.

Team care The patient is the most important member of the team by her compliance The patient

Control of diabetes in pregnancy Diet Exercise Insulin

Antenatal care Regular visits Regular visits Tight glucose control Tight glucose control Pre-meal glucometery Pre-meal glucometery Diet and insulin Diet and insulin Medical condition Medical condition Complications Complications Medical Medical Obstetric Obstetric Fetal assessment Fetal assessment Maturity Maturity Wellbeing Wellbeing Initial visit 1.Careful dating 2.White’s staging 3.Obstetric history 4.Funduscopy ** 5.Blood pressure 6.Urinalysis & culture ** 7.HbA1c **

3- Fetal Surveillance  Ultrasound scan  CTG  Biophysical Profile Starting 32 week gestation, weekly

Diet control kcal/kg ideal wt kcal/kg ideal wt 50% carbohydrate 50% carbohydrate 20% protein 20% protein 30% fat 30% fat Adjust for work Adjust for work 3 meals and 3 snacks 3 meals and 3 snacks Test for sugar before meals Test for sugar before meals Artificial sweeteners, high-fiber, low salt diet Artificial sweeteners, high-fiber, low salt diet What worsen diabetes 1.Infection 2.Lack of exercise 3.Drugs 4.Stress of life 5.Smoking Your aim is not weight reduction, but proper glycemic control Proper weight gain is 1 Ib/mo in first half & 1 Ib/wk in second half

Exercise for diabetics Advantage Exercising muscle utilizes glucose without insulin Exercising muscle utilizes glucose without insulin Synergistic with insulin Synergistic with insulin Improves metabolic control Improves metabolic control Improve the mood and well-being Improve the mood and well-beingDisadvantage Exercise-induced hypoglycemia Exercise-induced hypoglycemia Vigorous exercise worsen metabolic control precipitates lactic acidosis Vigorous exercise worsen metabolic control precipitates lactic acidosis Strenuous exercise diverts blood to the muscles; it can cause IUGR Strenuous exercise diverts blood to the muscles; it can cause IUGR Regular exercise improves the outcome of pregnancy in diabetics but strenuous one disproves it

Contraindication for exercise in pregnant diabetics Medical CVS diseases CVS diseases Retinopathy Retinopathy Nephropathy NephropathyObstetric PIH PIH Over distended uterus Over distended uterus History of premature labour History of premature labour

Insulin therapy Human insulin (Actrapid, Initard 1/1, Mixatard 2/1) Human insulin (Actrapid, Initard 1/1, Mixatard 2/1) Intermittent dosing Intermittent dosing Twice daily doses (Lewis) Twice daily doses (Lewis) Before breakfast 2/3 dose (NPH: Regular 2:1) Before breakfast 2/3 dose (NPH: Regular 2:1) Before dinner 1/3 dose (NPH: Regular is 1:1) Before dinner 1/3 dose (NPH: Regular is 1:1) Thrice daily doses (Jovanovic) Thrice daily doses (Jovanovic) Before breakfast 2/3 dose (NPH: Regular 2:1) Before breakfast 2/3 dose (NPH: Regular 2:1) Before lunch 1/6 dose (Regular) Before lunch 1/6 dose (Regular) Before dinner 1/6 dose (NPH) Before dinner 1/6 dose (NPH) Continuous insulin infusion pump (CII pump) Continuous insulin infusion pump (CII pump) Daily dosage is calculated according to gestational age, severity of diabetes and actual body weight.

2- Prenatal  Screen for gestational diabetes ideally in all pregnancies ( controversy over which test and whether just at weeks): OGTT is diagnostic test  Regular capillary glucose series  Avoid oral hypoglycemic agent  Appropriate diet  Amend insulin regimen to keep capillary glucose values as normal as possible  Instruct partners/relatives in glucagon use for hypoglycemic attacks

2- Prenatal  Baseline renal and possibly cardiac function  Randomized trials of low dose aspirin in women with vascular disease are awaited  Regular ophthalmologic review  Monitor for hypertensive disease  Fetal surveilance - Normality -Growth -Well-being(NST,BPS) - Umbilical artery blood flow - Normality -Growth -Well-being(NST,BPS) - Umbilical artery blood flow  Gestational diabetics: initially try to control with diet rather than insulin; otherwise, as for established diabetics

Vaginal Vaginal Spontaneous or induced Spontaneous or induced Shoulder dystocia develops at lower birth weights Shoulder dystocia develops at lower birth weights Caesarean section Caesarean section Planned Planned Urgent Urgent Neonatologist should be available Neonatologist should be available

Delivery Induction of labor at 38 weeks, as PNM starts to increase steadily afterward, for IDDM and GDM on treatment Induction of labor at 38 weeks, as PNM starts to increase steadily afterward, for IDDM and GDM on treatment If GDM on diet control with no complication allow till term If GDM on diet control with no complication allow till term Timing of delivery depends on Timing of delivery depends on MotherFetus Vascular disease Glycemic control Obstetric history MaturityEFWBPP

Intrapartum care Two infusion sets Two infusion sets G.I.K. 10% glucose + 10 I.U insulin + 10 mmol K G.I.K. 10% glucose + 10 I.U insulin + 10 mmol K 1-2 hourly blood sugar check and infusion adjustment according to level 1-2 hourly blood sugar check and infusion adjustment according to level keep the blood sugar mg/dl keep the blood sugar mg/dl CTG during labor & delivery CTG during labor & delivery

Post-partum care Readjust the dose of insulin Readjust the dose of insulin Encourage breast feeding Encourage breast feeding Reassess the glycemic status Reassess the glycemic status Give a suitable contraceptive Give a suitable contraceptive Weight reduction to delay NIDDM Weight reduction to delay NIDDM Follow-up for NIDDM Follow-up for NIDDM

 Hypoglycemia  Respiratory Distress Syndrome  Hypocalcemia  Hypomagnesemia  Jaundice Requiring admission to nursery for monitoring and Rx