1. Diabetes in Pregnancy Dr. Priyanka Kalra Resident Dr. C. P. Kachchwa Assoc. Prof. Dr. (Mrs.) H. V. Singh Prof. Dr. (Mrs.) Sumitra Bora Prof. & Head Ob. & Gyn. Department Dr. S. N. Medical College Jodhpur, Rajasthan, India Jodhpur, Rajasthan, India

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 patient 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 degrees 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.  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

5. 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

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 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. Carbohydrate Metabolism in Early Pregnancy  In early pregnancy, carbohydrate metabolism is affected promptly by a rise in serum levels of estrogen and progesterone that results in pancreatic cell hyperplasia and increased insulin secretion, resulting in hypoglycemia.  These alterations are anabolic and promote storage of glycogen.

8. In late pregnancy, there are raised levels of hormones like human placental lactogen(hpl), prolactin and cortisol, all of which are diabetogenic. Human placental lactogen [HPL] has insulinotropic and lipolytic properties owing to which it causes lipolysis of fat, sparing glucose and amino acid to the fetus. In late pregnancy, there are raised levels of hormones like human placental lactogen(hpl), prolactin and cortisol, all of which are diabetogenic. Human placental lactogen [HPL] has insulinotropic and lipolytic properties owing to which it causes lipolysis of fat, sparing glucose and amino acid to the fetus.

9. In late pregnancy, if there is inadequate insulin reserve, the interaction between placental HPL and insufficient maternal insulin result in impaired glucose tolerance for the mother. Estrogen, Progesterone and Cortisol all promote gluconeogenesis and impair peripheral utilization of glucose. Lastly, placenta contains enzyme insulinase, which degrades insulin. In late pregnancy, if there is inadequate insulin reserve, the interaction between placental HPL and insufficient maternal insulin result in impaired glucose tolerance for the mother. Estrogen, Progesterone and Cortisol all promote gluconeogenesis and impair peripheral utilization of glucose. Lastly, placenta contains enzyme insulinase, which degrades insulin.

10. Who 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 24 th and 28 th weeks of pregnancy or earlier if any of the risk factors are present.

11. 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

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

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

14. Effect of GDM on the Fetus  Congenital abnormalities  Neonatal hypoglycemia  Macrosomia (big baby syndrome > 4 Kg or >8 lb 13 oz)  Jaundice  Polycythemia / hyperviscosity syndrome  Hypocalcemia, hypomagnesemia  Birth trauma (due to macrosomia and shoulder dystocia)  Prematurity  Hyaline membrane disease  Apnea and bradycardia

15. Complications in 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

16. Effects of GDM on Neonates  Respiratory distress  Hypoglycemia  Hypocalcemia  Hyperbilirubinemia  Cardiac Hypertrophy  Long term effects on cognitive development

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. 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

19. 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

20. Screening Test Oral Glucose Tolerance Test (OGTT): Measurement of plasma glucose after ingesting 100 g of glucose. 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;144:768-73. > 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

21. *2 or more criteria met = positive diagnosis (cutoff points in mg/dl) † 1 or more criteria met = positive diagnosis

22. The Drawbacks to This Criteria  1) Number of blood samples drawn are too many for screening for subsequent Oral GTT to confirm diagnosis  2)They had to visit the centre on 2 occasions a) for screening b) diagnostic procedure  Due to the requirement of two visits, the phenomenon of no show occurs. Therefore a single step procedure is preferred.

23. WHO Procedure To standardize the diagnosis of GDM, WHO devised the 75 gm oral 2 hr glucose tolerance test (GTT) with a threshold plasma glucose concentration of >140 mg% at 2 hours

25. 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

26. 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: These are venous plasma targets, not glucometer targets.

27. Why These Tight Glycemic Targets? Prospective study in type-1 patients with pregnancy Prospective study in type-1 patients with pregnancy

28. 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

29. 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

30.  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 Medical Nutrition Therapy

31. 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.

32. Aims and Objectives 1) Early detection of GDM, by screening all the pregnant women attending the antenatal outdoor. 2) Reduced incidence of the many fetal complications, eg Macrosomia (7-17%), fetal hyperbilirubinemia, hypoglycemia, hypocalcemia, hypomagnesemia, etc. 3) Study the effect of GDM on the onset of labor, be it spontaneous or induced, and on the progress of labor.

33. 4 4) Reduced maternal morbidity and mortality. 5) Role in preventive medicine: it is well established that, of the women diagnosed with GDM, a number are predisposed to develop type 2 DM later in their lives. So these women can be educated to modify their lifestyles so as to prevent or postpone the occurrence of type 2 DM.

34. Method In the antenatal clinic, after undergoing the preliminary clinical examination, the patient is to be given a 75 gm oral glucose load (without regard given to the time of last meal). A venous blood sample is collected at 2 hrs for estimating plasma glucose level by the GOD-POD method. GDM is diagnosed if the 2 hr plasma glucose level is greater than or equal to 140 mg%.

35.  All women found to have 2 hr plasma glucose levels > or = 140 mg% will be diagnosed as having GDM. Those having plasma glucose levels> 200 mg% will be considered i preGDM or DM.  Those with plasma glucose levels between 140 and 199 mg% are considered to be cases of GDM; these women will be given nutrition therapy for 2 weeks. If the nutrition therapy fails to achieve control (that is, if fasting plasma glucose levels are more than 90 mg% and post meals greater than 200 mg%), the patient will be started on Insulin.

36. 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

37. Fetal Monitoring  Baseline ultrasound: fetal size  Ultrasound evaluation of neural tube defects and other congenital malformations should begin by 15-21 weeks  At 18-22 weeks: fetal anatomic survey, major malformations  At 20-22 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

38. 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

39.  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: 80-120 mg/dl (capillary: 70-110mg/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 Management of Labor and Delivery

40.  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

41. 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

42.  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