Diabetes in Diabetes in PregnancyPregnancy

Dr Thomas Paul MD Dr Thomas Paul MD DM (Endo)DM (Endo) Dr. Mathew John MD DM(Endo)Dr. Mathew John MD DM(Endo) Department of EndocrinologyDepartment of Endocrinology Christian Medical CollegeChristian Medical College VelloreVellore

Pregnancy may be complicated by diabetes

in two distinct forms: Gestational diabetes mellitus (GDM) is defined as glucose intolerance of varying severity with onset or first recognition during pregnancy. This subset constitutes 90% of women with pregnancies complicated by diabetes. The most important perinatal concern in this group is macrosomia with resulting birth trauma. More than 50% women ultimately develop diabetes in the ensuing 20 years and this is linked with obesity. Pre-gestational diabetes is diabetes that antedates pregnancy. Pregnancies which are complicated by pre-gestational diabetes, type-1 or type-2, carry an additional risk to both mother and fetus beyond the effects on fetal growth and development in mid and late pregnancy.

ClassificationClassification Pregestational diabetes: A lady with known diabetes who

conceives while on treatment with diet, oral hypoglycemic agents or insulin.

Type 1 DM, Type 2 DM, Secondary DM Gestational diabetes mellitus is defined as glucose

intolerance of variable degree with onset or first recognition during pregnancy. Some patients with fasting hyperglycemia detected early in pregnancy may be missed cases of diabetes that predated pregnancy. Women found early in pregnancy to have gestational diabetes are a high-risk subgroup.

GDM varies worldwide and among different racial and ethnic groups within a country. Variability is partly because of the different criteria and screening regimens Prevalence : India: 0.56% -6% (Ramachandran A et al 1994; Hill et al., 2005) USA: increased from 2.1–4.1% in the period 1994 to 2002 with significant increases in all racial/ethnic groups (Dabelea et al., 2005). Native Americans, Asians, Hispanics, African-American, Aboriginal women are at higher risk (Ferrara, 2007).

Magnitude of problem: GDM

Ramachandran A, Snehalatha C, Shymala P, Vijay V, Viswanathan M. Prevalence of diabetes in pregnant women--a study from southern India. Diabetes Res Clin Pract. 1994;25:71-74.

Hill JC, Krisgnaveni GV, Annamma I, Leary SD, Fall CH. Glucose tolerance in pregnancy in South India: relationships to neonatal anthropometry. Acta Obstet Gynecol Scand. 2005;84:159-65

Dabelea, D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS. Increasing Prevalence of Gestational Diabetes Mellitus (GDM) Over Time and by Birth Cohort. Diabetes Care 2005;28:579-584

Ferrara A: Increasing prevalence of gestational diabetes mellitus. Diabetes Care 2007;30:S141-S146

Risk Factors for gestational diabetes screening

1. Strong family history of diabetes

2. Women who have given birth to large infants (>4 kg; 8 lbs 13 oz)

3. History of recurrent fetal loss

4. Persistent glycosuria

5. Age > 25 years

6. Past history of glucose intolerance or diabetes in a previous pregnancy

Risk Factors for gestational diabetes screening

7. Obesity; overweight women (>15% of non-pregnant ideal body weight)

8. Ethnic group with a high prevalence of diabetes (e.g. Pima Indians, Asians, Hispanic)

9. History of stillbirth, unexplained neonatal death, congenital malformations, prematurity.

10. History of pre-eclampsia or polyhydraminos11. Chronic hypertension12. Recurrent severe moniliasis or urinary tract infection13. History of traumatic delivery with an associated neurological

disorder in the infant

Whom to screen? Risk stratification

Low risk: no screening Average risk: at 24-28 weeks

High risk: as soon as possible

Screening is ideally initiated between the 24th and 28th weeks of pregnancy or earlier if any of the risk factors are present.

Age <25 years

Weight normal before pregnancy

Member of an ethnic group with a low prevalence of GDM

No known diabetes in first-degree relatives

No history of abnormal glucose tolerance

No history of poor obstetric outcome

Low risk for GDM

High risk for GDM

Marked obesity Prior GDM Glycosuria Strong family history Ethnic group with high diabetes prevalence

Intermediate risk for GDM

Must exhibit one risk factor from the list in slide 5.

All Indian women and women of Indian origin should be screened for gestational diabetes mellitus

as they belong to a high risk ethnicity

Screening test Glucose Challenge Test (GCT): An excellent screening test for gestational diabetes is the measurement of plasma glucose 1 hour after ingesting 50 g of glucose.

A plasma glucose level obtained one hour after a 50 g glucose load administered at any time of the day without regard to the time since the last meal, has become a well validated and widely applied screening procedure for women between 24 and 28 weeks of gestation.

Using a cut-off value > 140 mg/dl identifies 80% women with GDM

Using a cut-off value > 130 mg/dl identifies 90% women with GDM

Women with elevated GCT values require a diagnostic oral glucose tolerance test

Screening testOral Glucose Tolerance Test (OGTT): Measurement of plasma glucose after ingesting 100 g of glucose.

Timing of Timing of measurementmeasurement

National Diabetes National Diabetes Data Group (1979)Data Group (1979)

Carpenter and Carpenter and Coustan (CC) 1982Coustan (CC) 1982

FastingFasting 105 mg/dl105 mg/dl 95 mg/dl95 mg/dl

1 hour1 hour 190 mg/dl190 mg/dl 180 mg/dl180 mg/dl

2 hour2 hour 165 mg/dl165 mg/dl 155 mg/dl155 mg/dl

3 hour3 hour 145 mg/dl145 mg/dl 140 mg/dl140 mg/dl

Classification: and diagnosis of diabetes mellitus and other categories of glucose intolerance: National Diabetes Data Group. Diabetes 1979;28:1039–1057Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol. 1982;144:768-73.

> 2 values must be abnormal; for at least 3 days prior to the test, the patient should have an unrestricted diet and unlimited physical activity. The patient should fast for 8 hours before the test. The CC criteria detects 54% more women with GDM than the NDDG criteria

Urine monitoring

Urine glucose monitoring is not useful in gestational diabetes Urine glucose monitoring is not useful in gestational diabetes mellitusmellitus

Urine ketone monitoring may be useful in detecting insufficient Urine ketone monitoring may be useful in detecting insufficient caloric or carbohydrate intake in women treated with calorie caloric or carbohydrate intake in women treated with calorie restrictionrestriction

Congenital abnormalities Neonatal hypoglycemia Macrosmia (big baby syndrome > 4 Kg or >8 lb 13 oz) Jaundice Polycythemia / hyperviscosity syndrome Hypocalcemia, hypomagnesemia Birth trauma (due to macrosmia and shoulder dystocia) Prematurity Hyaline membrane disease Apnea and bradycardia

The risk of fetal anomalies is not increased in GDM patients. However, the risks of unexplained still births (during the last 4-8 weeks of gestation) are similar to pre-gestational diabetes.

Effects of GDM on the fetusEffects of GDM on the fetus

Effects of GDM on neonates

Respiratory distress

Hypoglycemia

Hypocalcemia

Hyperbilirubinemia

Cardiac Hypertrophy

Long term effects on cognitive development

Macrosomic infant

Macrosomia (large for gestational age or big baby syndrome)

(birth weight >90% percentile for gestational age)

Macrosomia is a result of persistent maternal hyperglycemia leading to fetal hyperglycemia and prolonged fetal hyperinsulinism. This stimulates excessive somatic growth mediated by insulin-like growth factors (IGFs). Macrosomia affects all organs except the brain.

Congenital abnormalities due to GDM Cardiac (most common): transposition of great vessels, Cardiac (most common): transposition of great vessels,

Ventricular septal defect, Atrial septal defectVentricular septal defect, Atrial septal defect Central nervous system (7.2%): spina bifida, Anencephaly, Central nervous system (7.2%): spina bifida, Anencephaly,

hydrocephalushydrocephalus Skeletal: cleft lip/palate, caudal regression syndromeSkeletal: cleft lip/palate, caudal regression syndrome Genitourinary tract: ureteric duplicationGenitourinary tract: ureteric duplication Gastrointestinal: anorectal atresiaGastrointestinal: anorectal atresia Renal agenesis, Duplex ureters, Cystic KidneyRenal agenesis, Duplex ureters, Cystic Kidney Situs inversusSitus inversus

Poor glycemic control at time of conception: risk factor

Caudal regression syndrome (abnormal development of lower spine)

Caudal regression syndrome

Pre-eclampsia: affects 10-25% of all pregnant women with GDM Infections: high incidence of chorioamnionitis and postpartum endometritis Postpartum bleeding: high incidence caused by exaggerated uterine distension Cesarian section more common due to fetal macrosmia and cephalo-pelvic disproportion Weight gain Hypertension MiscarriagesThird trimester fetal deaths Long term risk of type-2 diabetes mellitus

Effects of GDM on the mother

Effect of pregnancy on diabetes

More insulin is necessary to achieve metabolic control

Progression of retinopathy: esp. severe proliferative retinopathy

Progression of nephropathy: especially if renal failure +

Increased risk of Coronary artery disease, and a high risk of maternal death in post MI patients

Cardiomyopathy

Patient educationPatient educationCornerstone in GDM managementCornerstone in GDM management

Instruct mother about maternal and fetal complicationsInstruct mother about maternal and fetal complications Medical Nutrition therapyMedical Nutrition therapy Glycemic monitoring: teach mother about self monitored blood Glycemic monitoring: teach mother about self monitored blood

glucose measurement and glycemic targetsglucose measurement and glycemic targets Pre-conception counselingPre-conception counseling Fetal monitoring: ultrasoundFetal monitoring: ultrasound Planning on deliveryPlanning on delivery Long term risksLong term risks

Glycemic control targets Tight glycemic control can reduce fetal risk. But, stringent glycemic control puts the mother at increased risk of hypoglycemic events and the fetus at risk of being small-for-gestational age.

American Diabetes Association Recommendations:

Fasting whole blood glucoseFasting whole blood glucose <95 mg/dl<95 mg/dl

1 hr postprandial blood glucose1 hr postprandial blood glucose <140 mg/dl<140 mg/dl

2 hr postprandial blood glucose2 hr postprandial blood glucose <120 mg/dl<120 mg/dl

These are venous plasma targets, not glucometer targets

Why these tight glycemic targets?Why these tight glycemic targets?

Prospective study in type-1 patients with pregnancyProspective study in type-1 patients with pregnancy

Fasting blood sugarFasting blood sugar MacrosomiaMacrosomia

>105 mg/dl>105 mg/dl 28.6 %28.6 %

95-105 95-105 10%10%

<95 mg/dl <95 mg/dl 3%3%

Self monitored blood glucose (SBMG)Self monitored blood glucose (SBMG)

4 4 times/day minimum, fasting and 1 to 2 hours after start of times/day minimum, fasting and 1 to 2 hours after start of mealsmeals

Maintain log bookMaintain log book Use a memory meterUse a memory meter Calibrate the glucometer frequentlyCalibrate the glucometer frequently

Medical Nutrition and Exercise therapy

Current weight in relation to Current weight in relation to ideal body weightideal body weight

Daily caloric intakeDaily caloric intake(kcal/kg)(kcal/kg)

Recommended pregnancy Recommended pregnancy weight gain (kg)weight gain (kg)

<80-90%<80-90% 36-4036-40 28-4028-40

80-120% (ideal)80-120% (ideal) 3030 25-3525-35

120-150%120-150% 2424 15-2515-25

>150% >150% 12-1812-18 15-2515-25

provide necessary nutrients for mother and fetus to ensure adequate gestational weight gain control glucose levels prevent starvation ketosis aerobic exercise, exercise that does not stress the trunk

Approximately 30 kcal/kg of ideal body weightApproximately 30 kcal/kg of ideal body weight

> 40-45% should be carbohydrates> 40-45% should be carbohydrates

6-7 meals daily (3 meals, 3-4 snacks). Bed time snack to prevent ketosis 6-7 meals daily (3 meals, 3-4 snacks). Bed time snack to prevent ketosis

Calories guided by fetal well being/maternal weight gain/blood sugars/ Calories guided by fetal well being/maternal weight gain/blood sugars/ ketonesketones

Energy requirements during the first 6 months of lactation require an Energy requirements during the first 6 months of lactation require an additional 200 calories above the pregnancy meal plan additional 200 calories above the pregnancy meal plan

Medical nutrition therapyMedical nutrition therapy

Insulin in GDM

Insulin used if fasting blood glucose >105 mg/dl or 1 hr postprandial blood glucose >120 mg / dl on a diet

Use basal bolus regime or pre-mixed insulin

Short acting insulins (e.g. Lispro and Aspart) can be used to achieve postprandial control

Long acting insulins (Glargine and Determir) are NOT licensed in pregnancy

Insulin requirements increase by 50% from 20-24 weeks to 30-32 weeks, after which insulin needs often stabilize.

Oral Hypoglycemic agents

Glyburide is a clinically effective alternative to insulin in GDM (Langer et al. 2000)

Metformin may be effective in GDM (Ratner et al., 2008; Coustan, 2007)

Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 2000;343:1134-8

Ratner RE, Christophl CA, Metzger BE, Dabalea D, Bennett PH, Pi-Sunyer X, Fowler S, Kahn SE, Diabetes Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab. 2008;93:4774-9

Coustan DR Pharmacological management of gestational diabetes: an overview. Diabetes Care. 2007;30 Suppl 2:S206-8.

Preconception counselingAll women with pre-existing type-1 or type-2 diabetes, when planning on pregnancy, should receive pre-conception counseling so that they understand the importance of achieving near-normal blood glucose before conception to reduce the risk of congenital malformations and spontaneous abortions.

Assess maternal and fetal risk Mother should learn self-administration of insulin and regular monitoring of blood glucose. Target: HbA1c < 7% Emphasize diet and exercise Folic acid supplementation: 5 mg/day Ensure no transmissible diseases: HBsAg, HIV, rubella Try and achieve normal body weight: diet/exercise Stop drugs: oral hypoglycemic drugs, ACE inhibitors, beta blockers and potentially teratogenic drugs

Clinical parameters checked at each visit

MedicationsMedications Pre-pregnancy weight Pre-pregnancy weight Weight gainWeight gain EdemaEdema PallorPallor Thyroid enlargementThyroid enlargement Blood pressure Blood pressure Fundal height Fundal height

Laboratory parameters to be

monitored at each visit

Hemoglobin

Blood Sugar

HbA1C (first trimester only)

Urine microscopy and albumin

Thyroid function (if goiter present)

Fetal monitoringFetal monitoring Baseline ultrasound : fetal sizeBaseline ultrasound : fetal size Ultrasound evaluation of neural tube defects and other Ultrasound evaluation of neural tube defects and other congenital malformations should begin by 15-21 weeks of congenital malformations should begin by 15-21 weeks of At 18-22 weeks: fetal anatomic survey, major malformationsAt 18-22 weeks: fetal anatomic survey, major malformations At 20-22 weeks: fetal echocardiogram for cardiac defectsAt 20-22 weeks: fetal echocardiogram for cardiac defects At 26 weeks onwards: ultrasound to evaluate fetal growth and At 26 weeks onwards: ultrasound to evaluate fetal growth and amniotic fluid volumeamniotic fluid volume Third trimester: Fetal surveillance to reduce risk of still birth: Third trimester: Fetal surveillance to reduce risk of still birth: include non-stress test, biophysical profile, maternal monitoring include non-stress test, biophysical profile, maternal monitoring of fetal activity, frequent USG for accelerated growthof fetal activity, frequent USG for accelerated growth abdominal: head circumference abdominal: head circumference

Timing of deliveryTiming of delivery

Small risk of late intra-uterine death even with good Small risk of late intra-uterine death even with good glycemic controlglycemic control

Delivery usually at 38 weeksDelivery usually at 38 weeks Beyond 38 weeks, increased risk of intrauterine death Beyond 38 weeks, increased risk of intrauterine death

without an increase in RDSwithout an increase in RDS

Vaginal delivery: preferredVaginal delivery: preferred Cesarian section only for routine obstetric indicationCesarian section only for routine obstetric indication

GDM alone is not an indication !GDM alone is not an indication ! >> 4.5 Kg fetus: Cesarean delivery may reduce the likelihood 4.5 Kg fetus: Cesarean delivery may reduce the likelihood

of brachial plexus injury in the infantof brachial plexus injury in the infant Unfavorable condition of the cervix is a problemUnfavorable condition of the cervix is a problem Maintain euglycemia during laborMaintain euglycemia during labor Maternal hyperglycemia in labor: fetal hyperinsulinemia and Maternal hyperglycemia in labor: fetal hyperinsulinemia and

worsen fetal acidosisworsen fetal acidosis Maintain sugars: 80-120 mg/dl (capillary: 70-110mg/dl )Maintain sugars: 80-120 mg/dl (capillary: 70-110mg/dl ) Feed patient the routine GDM diet Feed patient the routine GDM diet Maintain basal glucose requirementsMaintain basal glucose requirements Monitor sugars 1-4 hrly intervals during labourMonitor sugars 1-4 hrly intervals during labour Give insulin only if blood sugar >120 mg/dlGive insulin only if blood sugar >120 mg/dl

Management of labor and deliveryManagement of labor and delivery

Glycemic management during labour

Later stages of labour: start dextrose to maintain basal nutritional requirements: 150-200 ml/hr of 5% dextrose

Elective Cesarian section: check fasting blood sugar; if within target range no insulin is needed; start dextrose drip

Continue hourly self monitored blood glucose Post delivery keep patients on dextrose-normal saline till fed No insulin unless sugars more than normal ( not GDM

targets ! )

Check blood sugars before discharge Breast feeding: helps in weight loss Lifestyle modification: exercise, weight reduction Oral glucose tolerance test at 6-12 weeks

postpartum: classify patients into normal/impaired glucose tolerance and diabetes

Preconception counseling for next pregnancy

Increased risk of cardiovascular disease,future diabetes and dyslipidemia

Post partum follow up

Hypoglycemia: 50 % of macrosomic infants 5–15 % optimally controlled GDM Starts when the cord is clamped Exaggerated insulin release secondary to pancreatic ß-cell

hyperplasia Increased risk: blood glucose during labor and delivery

exceeds 90 mg/dl

Anticipate and treat hypoglycemia in the infant

Immediate management of neonate

Management of neonateManagement of neonate

Hypoglycemia <40 mg/dl Encourage early breast feeding If symptomatic give a bolus of 2- 4 ml/kg, IV, 10% dextrose Check after 30 minutes, start feeding IV dextrose : 6-8 mg/kg/min infusion Check for calcium, if seizure/irritability/RDS Examine infant for other congenital abnormalities

Long term risk: offspring

Increased risk of obesity and abnormal glucose Increased risk of obesity and abnormal glucose tolerance due to changes in fetal islet cell function tolerance due to changes in fetal islet cell function

Encourage breast feeding: less chance of obesity in Encourage breast feeding: less chance of obesity in later lifelater life

Lifestyle modificationLifestyle modification

Gestational diabetes is a common problem in worldwide

Risk stratification and screening is essential in all pregnant women, particularly those from ethnicities with increased risk

Tight glycemic targets are required for optimal maternal and fetal outcome

Patient education is essential to meet targets

Long term follow up of the mother and baby is essential

Conclusion

                                                                                                               

                

17 pound baby born to Brazilian diabetic mother Courtesy: MSNBC News ServicesJan. 24, 2005