1. Diabetes in Pregnancy Dr Thomas Paul MD DM (Endo)
Dr. Mathew John MD DM(Endo)
Department of Endocrinology
Christian Medical College
Vellore

2. 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.

3. Classification
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.

4. Magnitude of problem: GDM
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).
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:
Ferrara A: Increasing prevalence of gestational diabetes mellitus. Diabetes Care 2007;30:S141-S146

5. Risk Factors for gestational diabetes screening
Strong family history of diabetes
Women who have given birth to large infants (>4 kg; 8 lbs 13 oz)
History of recurrent fetal loss
Persistent glycosuria
Age > 25 years
Past history of glucose intolerance or diabetes in a previous pregnancy

6. 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 polyhydraminos
11. Chronic hypertension
12. Recurrent severe moniliasis or urinary tract infection
13. History of traumatic delivery with an associated neurological disorder in the infant

7. Whom to screen? Low risk: no screening Average risk: at 24-28 weeks
Risk stratification
Low risk: no screening
Average risk: at 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.

8. Low risk for GDM 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

9. Intermediate risk for GDM
Must exhibit one risk factor from the list in slide 5.
High risk for GDM
Marked obesity
Prior GDM
Glycosuria
Strong family history
Ethnic group with high diabetes prevalence

10. as they belong to a high risk ethnicity
All Indian women and women of Indian origin should be screened for gestational diabetes mellitus
as they belong to a high risk ethnicity

11. 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

12. Screening test
Oral Glucose Tolerance Test (OGTT): Measurement of plasma glucose after ingesting 100 g of glucose.
Timing of measurement
National Diabetes Data Group (1979)
Carpenter and Coustan (CC) 1982
Fasting
105 mg/dl
95 mg/dl
1 hour
190 mg/dl
180 mg/dl
2 hour
165 mg/dl
155 mg/dl
3 hour
145 mg/dl
140 mg/dl
> 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
Classification: and diagnosis of diabetes mellitus and other categories of glucose intolerance: National Diabetes Data Group. Diabetes 1979;28:1039–1057
Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol. 1982;144:

13. Urine monitoring
Urine glucose monitoring is not useful in gestational diabetes mellitus
Urine ketone monitoring may be useful in detecting insufficient caloric or carbohydrate intake in women treated with calorie restriction

14. Effects of GDM on the fetus
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.

15. Effects of GDM on neonates
Respiratory distress
Hypoglycemia
Hypocalcemia
Hyperbilirubinemia
Cardiac Hypertrophy
Long term effects on cognitive development

16. 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.

17. Congenital abnormalities due to GDM
Cardiac (most common): transposition of great vessels, Ventricular septal defect, Atrial septal defect
Central nervous system (7.2%): spina bifida, Anencephaly, hydrocephalus
Skeletal: cleft lip/palate, caudal regression syndrome
Genitourinary tract: ureteric duplication
Gastrointestinal: anorectal atresia
Renal agenesis, Duplex ureters, Cystic Kidney
Situs inversus
Poor glycemic control at time of conception: risk factor

18. Caudal regression syndrome (abnormal development of lower spine)

19. Caudal regression syndrome

20. Effects of GDM on the mother
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
Miscarriages
Third trimester fetal deaths
Long term risk of type-2 diabetes mellitus

21. 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

22. Patient education Cornerstone in GDM management
Instruct mother about maternal and fetal complications
Medical Nutrition therapy
Glycemic monitoring: teach mother about self monitored blood glucose measurement and glycemic targets
Pre-conception counseling
Fetal monitoring: ultrasound
Planning on delivery
Long term risks

23. 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 glucose
<95 mg/dl
1 hr postprandial blood glucose
<140 mg/dl
2 hr postprandial blood glucose
<120 mg/dl
These are venous plasma targets, not glucometer targets

24. Why these tight glycemic targets?
Prospective study in type-1 patients with pregnancy
Fasting blood sugar
Macrosomia
>105 mg/dl
28.6 %
95-105
10%
<95 mg/dl 3%

25. Self monitored blood glucose (SBMG)
4 times/day minimum, fasting and 1 to 2 hours after start of meals
Maintain log book
Use a memory meter
Calibrate the glucometer frequently

26. Medical Nutrition and Exercise therapy
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
Current weight in relation to ideal body weight
Daily caloric intake
(kcal/kg)
Recommended pregnancy weight gain (kg)
<80-90%
36-40
28-40
80-120% (ideal) 30
25-35 % 24
15-25
>150%
12-18

27. Medical nutrition therapy
Approximately 30 kcal/kg of ideal body weight
> 40-45% should be carbohydrates
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/ ketones
Energy requirements during the first 6 months of lactation require an additional 200 calories above the pregnancy meal plan

28. 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 weeks to weeks, after which insulin needs often stabilize.

29. 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.

30. Preconception counseling
All 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

31. Clinical parameters checked at each visit
Medications
Pre-pregnancy weight
Weight gain
Edema
Pallor
Thyroid enlargement
Blood pressure
Fundal height

32. Laboratory parameters to be monitored at each visit
Hemoglobin
Blood Sugar
HbA1C (first trimester only)
Urine microscopy and albumin
Thyroid function (if goiter present)

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

34. Timing of delivery
Small risk of late intra-uterine death even with good glycemic control
Delivery usually at 38 weeks
Beyond 38 weeks, increased risk of intrauterine death without an increase in RDS

35. Management of labor and delivery
Vaginal delivery: preferred
Cesarian section only for routine obstetric indication
GDM alone is not an indication !
> 4.5 Kg fetus: Cesarean delivery may reduce the likelihood of brachial plexus injury in the infant
Unfavorable condition of the cervix is a problem
Maintain euglycemia during labor
Maternal hyperglycemia in labor: fetal hyperinsulinemia and worsen fetal acidosis
Maintain sugars: mg/dl (capillary: mg/dl )
Feed patient the routine GDM diet
Maintain basal glucose requirements
Monitor sugars 1-4 hrly intervals during labour
Give insulin only if blood sugar >120 mg/dl

36. Glycemic management during labour
Later stages of labour: start dextrose to maintain basal nutritional requirements: 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 ! )

37. Post partum follow up 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

38. Immediate management of neonate
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

39. Management 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

40. Long term risk: offspring
Increased risk of obesity and abnormal glucose tolerance due to changes in fetal islet cell function
Encourage breast feeding: less chance of obesity in later life
Lifestyle modification

41. Conclusion 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

42. 17 pound baby born to Brazilian diabetic mother
                                                                                                                               
17 pound baby born to Brazilian diabetic mother
Courtesy: MSNBC News Services
Jan. 24, 2005