Gestational Diabetes Management case studies by diabetesasia.org

1. Objectives Discuss the safety of continuing pre-pregnancy medications Pharmacological Decide when antihyperglycemic medication is required during pregnancy Determine what antihyperglycemic medication to Management use Discuss initial dosing and adjustment of dose Discuss insulin administration, storage Lipids and Blood pressure Replacements Dyslipidemia Statins must be stopped § Reduction of saturated fat intake, no trans fat intake, § Preferably prior to pregnancy or cholesterol intake < 200mg/day § As soon as pregnancy determined § Weight control § Physical activity ACE inhibitors and ARBs (angiotensin II receptor blockers) must be stopped § Preferably prior to pregnancy or Hypertension § As soon as pregnancy determined § Reduce salt intake § Calcium channel blockers, labetalol, hydralazine and ACEI/ ARBs may cause renal failure in the methyldopa. fetus CDA, 2013 CDA, 2013 Kitzmiller, Block et al, 2008 51

2. Triglycerides Insulin Triglycerides may double by 20 weeks Indicated when target blood glucose levels not attained with diet and physical activity after 2 weeks Cholesterol, LDL and HDL may increase 10 -20% Human insulin should be used – less transfer of insulin Initiate treatment if triglycerides over 1000mg/dl antibodies § Intensive glycemic control § Fish oil supplement Rapid acting insulin analogues (lispro and aspart) have been shown to be safe in pregnancy Fibrates and niacin are best avoided during pregnancy § Improve postprandial levels § Lower risk of postprandial hypoglycemia Fetal outcomes the same with human insulin (soluble) Goldenberg, Benderly, Goldbourt, 2008 or rapid acting analogues Kitzmiller, Block et al, 2008 Insulin Starting insulin in GDM Long acting insulin analogues If fasting high – start NPH or detemir at bedtime • detemir has been approved for use in pregnancy If postprandial high – start soluble or rapid acting • glargine has not yet been approved before meal. Few studies on safety of long acting analogues in § Start with 4 units pregnancy § Titrate 1-2 units/every 2 days until targets are reached Usual recommendation is to use NPH or detemir Educate as basal insulin § Administration § Storage Premix insulins are an alternative but lack the flexibility of a basal bolus regimen § Hypoglycemia 52

3. Insulin Syringe • Correct syringe must be used for the strength of the insulin • if using 100u/1 ml insulin then must have a 100u/1ml syringe, • if using 40u/1ml insulin must have a 40u/1ml syringe. • Usually disposable – intended for 1 use only • Insulin pens are convenient alternatives to syringes but are more expensive • Easier to teach • Fewer mistakes with dosages 53

4. Insulin Practicalities Precautions Storage • Insulin strength may vary (U40, U100) • Ensure the syringe matches the strength! • One month at room temperature once the vial has been opened or • Clear insulins kept in fridge • Long acting insulin analogues • Must never be frozen • Regular/soluble insulin • Rapid acting insulin analogues • Store away from source of heat • Cloudy insulin (should not be used if clumps do not • If refrigerator not available, store in clay pot dissolve on mixing • May be damaged by direct sunlight or vigorous shaking • NPH or N • Premixed insulin • Pre-drawn syringes can be kept for one month in fridge (provided • Identify and differentiate insulin type power supply reliable) Glucose lowering medications Sulfonylurea – glibenclamide (glyburide) § Minimal transfer across the placenta § Not associated with neonatal hypoglycemia § Must be balanced with meals and snacks to prevent hypoglycemia § Higher incidence of pre-eclampsia Good control achieved…but Jacobson et al . 2005 54

5. However… Glucose lowering medications Latest evidence suggests: ? glibenclamide is associated with worse outcomes compared to insulin and metformin Metformin Need more studies in this area § Does cross the placenta Hence glibenclamide is not recommended in the routine management of GDM § Does not appear to have adverse effects on the fetus § May be used in polycystic ovarian syndrome to improve Feig, Moses, 2011 fertility and decrease spontaneous abortion rate Balsells et al, 2015 However… Metformin vs Insulin (MiG Trial) Neonatal complications did not vary between the 2 subject groups. What is the effect on the babies? • Less severe hypoglycemia in the infants of mothers on metformin. • Women on metformin gained less weight Unknown as to whether the use of metformin • Preterm birth was more common in the metformin group, but there during pregnancy is was no increase in other complications. § Beneficial • 76% of women who used metformin were more likely to say they would use metformin in a subsequent pregnancy than were women § Neutral on insulin (27.2%). § Deleterious 46.3% of women on metformin had to be on supplemental insulin as Need more studies in this area well. The conclusion of this study was that metformin Metformin is therefore not recommended as a first was a safe option for GDM, and it was more line therapy for GDM agreeable to the patient. Feig, Moses, 2011 Rowan Hague Gao et al. 2008 55

6. Other oral agents Final word on oral agents There is insufficient data on the use of other If a woman is on oral agents when diagnosed with antidiabetic agents such as GDM • meglitinides, -Discontinue them • alpha glucosidase inhibitors, • thiazolidinediones, -Start diet and exercise plan • GLP-1 agonists and DPP-4 inhibitors -Monitor blood glucose The use of these agents in pregnancy cannot -Start insulin be recommended References Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 Clinical practice guidelines for the prevention and management of diabetes in Canada; Diabetes and pregnancy. Can J of Diabetes. 2013;37(suppl 1):S168-183. Feig DS, Moses RG. Metformin during pregnancy. Diabetes Care. 2011;34:2329 Goldenberg I, Benderly M, Goldbourt U. Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag. 2008 February;4(1):131–141. Jacobson et al - Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization, American Journal of Obstetrics and Gynecology 2005 Kitzmiller JL, Block JM, Catalano PM, et al. Managing preexisting diabetes for pregnancy: Summary of evidence and consensus recommendations for care. Diabetes Care. 2008;31(5):1060-1079. Rowan JA, Hague WM, Gao W. et al. Metformin versus Insulin for the Treatment of Gestational Diabetes. NEJM 2008;358:2003-15 56

7. Objectives Discuss causes, prevention strategies and Complications treatment of hypoglycemia for those women on insulin Hypoglycemia Discuss premature labour, recognizing Premature Labour contractions, and action to take Preeclampsia Discuss diagnosis and treatment of preeclampsia Definition of hypoglycemia Risk of hypoglycemia (1 of 3) 1. The development of autonomic or Only those taking glucose-lowering medicines neuroglycopenic symptoms or insulin are at risk 2. Low plasma glucose (less than 4.0 mmol/L or Risk increases with: 72 mg/dl) • Not enough carbohydrate consumption 3. Symptoms resolved by administration of • Late or missed meal carbohydrate • Fasting or malnourishment • Too much insulin • Prolonged or unplanned activity Cryer, Davis, Shamoon, 2003 57

8. Canadian Diabetes Association, 2013 Effect Of Hypoglycemia On Fetus Fetal heart rate, as well as fetal movements and placental perfusion appear to be unchanged during conditions of maternal hypoglycemia in the range of 2.5 – 3.0 mmol/L (45–55 mg/dL) Coustan, 2009 Diamond, Reece et al, 1992 Nisell, Persson, et al1994 Reece, Hagav, et al 1995 58

9. Treatment Severe • 20 g glucose • Glucagon 1ml SC or IM; increases BG by 3 -12 mmol/L (54-216 mg/dl) over 60 min • IV dextrose- 20 to 50 ml of 50% dextrose over 2 to 3 minutes; immediate response is seen • Manage seizure- place person on their side if not too agitated Canadian Diabetes Association, 2013 Premature Labour Follow-up management Preterm labour in GDM – can use steroids and • Meal or snack (15 to 20 g carbohydrate + a protein tocolysis as for other pregnancies source) Preferably avoid betamimetic as tocolytics • Next dose of insulin taken as usual if cause is known and hypo was mild Nifidepine is a good choice • Consider reducing next dose of insulin if hypo was Both steroids / tocolytics can push glucose up so severe need to monitor closely and cover with insulin / increasing dose of insulin • Assess cause and prevent recurrence • Avoid BG levels < 4 mmol/L (72 mg/dL) Rule out UTI as a risk factor for preterm labour 59

10. Preeclampsia • Women with GDM are at increased risk of preeclampsia; this is partly due to the increased insulin resistance • It is possible that this increase could be Delivery accounted for by the fact that their age and BMI predispose them to GDM as well as hypertension. • Monitor BP & urine albumin every visit Hollander 2007 Timing of delivery – the same for all? • Women with diabetes before pregnancy are at Objectives increased risk • In GDM perinatal mortality rates lower Discuss when to deliver infant • If insulin requiring, best to use approach similar to pregestational DM Discuss options for inducing labour • GDM managed on diet and exercise alone possibly not Discuss implications of Caesarian section at any greater risk from baseline • Depends on severity and duration of diabetes as well as co morbidities 60

11. Timing of delivery Consider…. TOO LATE? Gestational specific risks for still birth continue to EARLY fall up to 38 weeks but increase slightly over 40 weeks LATE RDS IUFD In insulin dependent women most would plan delivery 38 - 39 weeks PREMATURITY MACROSOMIA Between 38 and 39 weeks § No difference in incidence of cesareans § More larger babies in one study § There is as yet not enough evidence that induction in diabetic pregnancies prevents fetal macrosomia In diet controlled GDM women most would be Mode of delivery comfortable to 40 weeks Matter of choice Withgood control and reassuring tests of well being some centres go on to 41 weeks High section rates – 30 – 80% averaging 50% in many centres Vaginal delivery is possible and safe § Previous obstetric history § EFW § Other clinical factors Induction of labour is a safe option Patel, Steer, Doyle et al. 2003 61

12. Monitoring labour References COMPLICATIONS Labour is a time of unpredictable glucose and insulin Canadian Diabetes Association Expert Committee. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diab 2013;37(suppl 1):S69-71 demands – risk of hypoglycemia Coustan, D, Glob. libr. women's med., (ISSN: 1756-2228) 2009; DOI 10.3843/GLOWM.10162 CryerP.E. Davis, S.N. Shamoon, H. Hypoglycemia in diabetes. Diabetes Care, 2003;26(6):1902 -1912 Sliding scale / infusion Diamond MP, Reece EA, Caprio S et al: Impairment of counterregulatory hormone responses to hypoglycemia in § Maintain plasma glucose below 110 mg/dl to avoid maternal pregnant women with insulin-dependent diabetes mellitus. Am J Obstet Gynecol 1992;166:70-77 hyperglycemia and subsequent foetal hypoglycemia Hollander M, Paarlberg KM, Huisjes AJM, 2007 Gestational Diabetes: A Review of the Current Literature and Guidelines Volume 62, Number 2 Obstetrical and Gynecological Survey Nisell H, Persson B, Hanson U, et al: Hormonal, metabolic and circulatory responses to insulin-induced hypoglycemia Careful intrapartum FHR monitoring in pregnant and nonpregnant women with insulin-dependent diabetes. Am J Perinatol 1994;11:231-236 Reece EA, Hagay Z, Roberts AB et al: Fetal Doppler and behavioral responses during hypoglycemia induced with the Pay attention to second stage – slow progress is a insulin clamp technique in pregnant diabetic women. Am J Obstet Gynecol 1995;172:151-155. red flag Saleh M., Grunberger, G. Hypoglycemia: A cause for poor glycemic control. Clinical Diabetes, 2001;19(4):161-167. DELIVERY Caution with instrumental delivery Jovanovic L, Knopp RH, Kim H, et al. Elevated pregnancy losses at high and low extremes of maternal glucose in early normal and diabetic pregnancy: evidence for a protective adaptation in diabetes. Diabetes Care 2005; 28:1113. Patel RR, Steer P, Doyle P, Little MP, Elliot P. Does gestation vary by ethnic group? A London-based study of over Be prepared for shoulder dystocia 122000 pregnancies with spontaneous onset of labour. Int J of Epid. 2003;33:107-113.DOI: 10.1093/ijc/dyg238. Jovanovic L. 2005 62

13. Objectives Discuss the immediate care of the infant Discuss the importance of breast feeding Post Partum Discuss follow up screening of the mother Discuss risk of IGT or diabetes in future Discuss follow up education for mother After delivery – the infant After delivery – the infant Watch for signs of hypoglycemia Usual care § Vital signs Check blood glucose – heel prick § Apgar scores § Within 1sthour after delivery § Pre-warmed incubator § After each of 1st4 feeds § Start breast feeding within 30 minutes for better latching Less than 2.6 mmol/L or 44 mg/dl defined as § Watch for jaundice – check bilirubin § If macrosomic, check calcium and magnesium on day 2 hypoglycemia Treatment of hypoglycemia § Topfeeding/glucose in water/ IV dextrose Seshiah, Balaji, 2006 Seshiah, Balaji, 2006 63

14. Breast feeding Encourage for all After delivery - mother Protects infant from over or undernutrition during early childhood Exogenous insulin not required after placenta is delivered May lower risk of § Obesity Blood glucose usually returns to normal § Hypertension Check fasting within 48 hours to rule out type 1 or § Cardiovascular disease type 2 diabetes § Diabetes Gunderson, 2007 Future pregnancies Post partum period Should be planned Education regarding birth control is needed Encourage mother to achieve healthy weight. • Healthy eating Encourage achieving healthy weight prior to • Adequate intake to sustain breast feeding conceiving again • Regular activity Check blood glucose levels well ahead of conception allowing time to normalize if necessary 64

15. Glucose tolerance testing Contraception Should be done 6-12 weeks post partum Fasting glucose testing is not sufficient to Any method of contraception can be safely used in identify all who have IGT or type 2 diabetes a woman with history of GDM § Only 34% of women with IGT or type 2 had elevated • Intrauterine devices are commonly used fasting glucose levels § 44% of those with type 2 had fasting less than 5.5 mmol/L (100 mg/dL) Progesterone-only oral contraceptives are the best choice within the first 6 weeks post partum OGTT should be done • They have the lowest risk of thrombosis • Preferred during breastfeeding Metzger, Buchanan, Coustan et al. 2007 CVD risk Postpartum education is key OGTT at 6-12 weeks Women with GDM may have many of characteristics of metabolic syndrome Managing risk factors § Obesity Hypertension, dyslipidemia, obesity, IGT should all § Hypertension be evaluated and treated § Dyslipidemia Birth control Preconception screening Annual screening for diabetes – 35-60% risk of type 2 within 10 years Metzger, Buchanan, Coustan et al. 2007 Metzger, Buchanan, Coustan et al. 2007 65

16. References Gunderson EP. Breastfeeding after gestational diabetes pregnancy. Diabetes Care. 2007;30(suppl 2):S161-168. Metzger BE, Buchanan TA, Coustan DR, De Leiva A, Hadden DR, Hod M. Summary and recommendations of the fifth international workshop-conference on gestational diabetes mellitus, Diabetes Care. 2007; 30(suppl 2):S251-260. Seshiah V, Balaji V, et al. Gestational Diabetes Mellitus – Guidelines. J Assoc Physic of India 2006;54:622-28. 66

17. Case study #1: Mrs. C Mrs. C is a 22 year old primigravida coming for her first antenatal checkup at 12 weeks of gestation. On examination, she is 152 cm tall and weighs 69 kg. BMI, 30 kg/m2 CASE STUDIES She does not have a family history of diabetes. •Does she need to be screened for diabetes? •If so, when? •What screening test is to be used? Mrs. C. Mrs. C Mrs. C had a fasting blood glucose done Mrs. C undergoes repeat testing at 26 weeks’ gestation. Her results are as follows. Her results on the 75 gm glucose load (fasting) are as follows. Time 0 hr (Fasting) Time 0 hr (Fasting) 1 hour 2 hour Glucose 4.7 (86) Glucose 4.8 (88) 10.3 (186) 8.9 (161) mmol/L(mg/dL) mmol/L(mg/dL) •Does she have GDM? •Does she have diabetes? •If yes, what treatment is indicated? •Does she have GDM? •When will you review her and using what tests? •Does she need to be tested again? •If so, when? 67

18. Mrs. C Mrs. C Mrs. C is put on 4 units of rapid acting insulin before After 2 weeks, her results were as follows breakfast and advised to monitor her blood glucose daily. She does well. Fasting blood glucose mmol/L 5.2 (93) (mg/dL 2 hour postprandial blood 8.6 (156) After 2 weeks, her reports are as follows. glucose mmolL (mg/dL) breakfast Fasting blood glucose mmol/L (mg/dl) 6.5 (118) 2 hour postprandial blood glucose 7 (126) •Is her glycemic control adequate? mmol/L(mg/dl) breakfast •What is the next line of treatment? •What other test can help assess level of glycemic control? •Is her glycemic control adequate? •What is the next line of treatment? Mrs. C Mrs. C Her insulin dose has stabilized Mrs. C is now on 6 units of NPH insulin at bedtime in § NPH 8 units at bedtime addition to 4 units of rapid acting insulin before breakfast. § rapid acting insulin 6 u before breakfast, 4 units before lunch She starts complaining of excess hunger during the early and 4 units before evening meal. hours of the morning. Mrs. C goes into labour at 39 weeks. Her reports are as follows. Should she have been induced earlier? mmol/L (mg/dL) Should a C-Section be considered? Fasting BG 3.3 (61) 2 hour postprandial BG 5.6 (102) How should her insulin be managed during labour •Are these values acceptable? and delivery? •What is the next line of treatment? 68

19. Case study #2: Mrs. S Mrs. C Mrs. S is a 35 year old nulliparous lady and has suffered Following delivery, blood glucose levels normalised and two miscarriages in the last three years. she was able to stop insulin. After the last miscarriage she was diagnosed with PCOS and has been on metformin since. After 6 weeks, she underwent an OGTT, the results of which are as follows. She did not test her blood glucose levels during either of Time 0 hour (Fasting) 2 hours her previous pregnancies. Glucose mmol/L 4.5 (82) 7.0 (127) (mg/dl) Her mother has diabetes. •What is the diagnosis? She presents at 12 weeks gestation •What is her risk of developing diabetes in the future? •When should she be tested next? What else do you need to know? Mrs. S Mrs. S Mrs S has an OGTT at 13 weeks gestation • Does she need to be screened for diabetes? Fasting 2 hour • If so, when? Glucose 6.0 (108) 9.0 (162) mmol/L(mg/dl) • What screening test is to be used? Are these results ok? • Should the metformin be continued? Should she be retested? When? • What is the purpose of metformin? What management strategies should be considered? 69

20. Mrs M Case Study #3: Mrs M Fasting BG at 6 weeks Fasting Mrs. M, 30/F – Primigravida 8.8 mmol/L (160 mg/dL) LMP: 13/10/12 EDC : 28/07/13 Regular cycles What would you advise now? Trial of MNT or medications right away? Spontaneous conception 10 months after marriage Any other tests? No family history of DM What risks to the pregnancy will you discuss with this lady? Mrs M MRS M – Blood glucose record Normal scan at 12 weeks with a low risk of Downs Gestational FBS mmol/L 1 h PPBS A1c Medication age (mg/dL) mmol/L(mg/dL) % 19- 20 week scan plus fetal echo was normal 15 5.9 (107) 6.9 (125) 8.1 Premix 70/30 18 - 0 - 18 + When will you advise next scan? Metformin 500 BD 18 7.1 (129) 10.1 (183) 7.2 22 - 0 - 22 + Metformin BD 19 5.3 (97) 9.6 (173) 26 - 0 - 20 + Glucose results as in next slide. Patient not very Metformin BD regular with SMBG and not following the meal 5.8 (105) 8.7 (157) 6.5 plan 70

21. Mrs M Mrs M She comes in with c/o discomfort and 29 week scan abdominal pain at 30 weeks How will you manage her now? Uterus is irritable with some tightening on and Ask to comment off Mrs M Uterine contractions settle. UTI picked up and treated with appropriate antibiotics Mrs M She is now 37 weeks FBS 5.5mmol/L (100mg/dL) 1 hr PPBS 8.3 mmol/L (150 Tocolytic – which drug and dose mg.dL) on Regular (soluble) 26-10-14 + NPH 0-0-12 Steroids – dose / concerns in GDM Comes in with decreased movements What would your approach be? 71

22. Case Study #4 Mrs. C, a 32 year old primigravida Reports for the first antenatal checkup. She is obese with a body mass index of 35 kg/m2, both her parents have diabetes. Her OGTT results are as follows. Time 0 hr (Fasting) 1 hour 2 hour Glucose 10.6 (192) 16.0 (288) 14.6 (263) mmol/L(mg/dL) Her HbA1c is 9.2%. • What type of diabetes does this patient have? • What is the ideal line of treatment? • What is the prognosis for the pregnancy and for future resolution of diabetes? 72

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34. Original Article jk"Vªh; LokLF; fe'ku WORLD DIABETES FOUNDATION WORLD DIABETES FOUNDATION Can the management of blood sugar levels in gestational diabetes mellitus cases be an indicator of maternal and fetal outcomes? The results of a prospective cohort study from India. 1 2 1 1 Rajesh Jain, Sanjeev Davey , Anuradha Davey , Santosh K. Raghav , Jai V. Singh 1 Gestational Diabetes, Prevention Control Project, Jain Hospital, Kanpur, Department of Community Medicine, 2 Muzaffarnagar Medical College and Hospital, Muzaffarnagar, Department of Community Medicine, Subharti Medical College, Meerut, Uttar Pradesh, India. BACKGROUND: Gestational diabetes mellitus (GDM) is emerging as an important public health problem in India owing to its increasing prevalence since the last decade. The issue addressed in the study was whether the management of blood sugar levels in GDM cases can predict maternal and fetal outcomes. A prospective cohort study was done for 2 year from October1, 2012, to September 31, 2014, at 198 diabetic screening units as a part of the Gestational Diabetes Prevention and Control Project approved by the Indian Government in the district of Kanpur, state of Uttar Pradesh. A total of 57,108 pregnant women were screened during their 24-28th weeks ofpregnancy by impaired oral glucose test. All types of maternal and perinatal outcomes were followed up in both GDM and non-GDM categories in the 2nd year (2013-2014) after blood sugar levels were controlled. differences between GDM cases and non-GDM cases were highly significant (P < 0.0001, relative risk > 1 in every case). Moreover, perinatal mortality also increased significantly from 5.7% to 8.9% when blood sugar levels increased from 199mg/dl and above. Perinatal and maternal outcomes in GDM cases were also significantly related to the control of blood sugar levels (P < 0.0001). Blood sugar levels can be an indicator of maternal and perinatal morbidity and mortality in GDM cases, provided unified diagnostic criteria are used by India laboratories. However, to get an accurate picture on this issue, all factors need further study. MATERIALS AND METHODS: It was seen that for all kinds of maternal and fetal outcomes, the RESULTS: CONCLUSION: It was seen that for all kinds of maternal outcomes suchas cesarean section, pregnancy-induced bypertension (PIH), premature baby unit (PBU) care, family H/O DM and antepartum hemorrhage / postpartum hemorrhage (APH / PPH), the differences between GDM and non-GDM cases were highly statistically significant (P < 0.0001, RR > 1 in every case). This was also seen in the outcomes of neonates in terms of perinatal death, stillbirth, neonatal death, congenital malformations, low gestation for age (LGA), low birth weight (LBW), jaundice. Here also the differences between GDM and non-GDM case were statistically significant (P < 0.0001, RR > 1 in every case) [Table 1]. In terms of H/O previous birth complication, again in the category of stillbirths and perinatal deaths both in GDM and non-GDM cases, the differences were statistically significant (P < 0.0001). However, in neonatal deaths, it was not significant in both GDM and non-GDM category (P > 0.05) [Table 2] As the blood sugar level rose above 120 mg/dl, perinatal mortality rose significantly as compared to previous perinatal loss (P < 0.0001). This increased significantly from (5.7% to 8.9%) when blood sugar level was >199 mg/dl [Table 3 and Figure 1]. significantly from (5.7% to 8.9%) when blood sugar level was >199 mg/dl [Table 3 and Figure 1]. It was seen that for all kinds of maternal outcomes suchas cesarean section, pregnancy-induced bypertension (PIH), premature baby unit (PBU) care, family H/O DM and antepartum hemorrhage / postpartum hemorrhage (APH / PPH), the differences between GDM and non-GDM cases were highly statistically significant (P < 0.0001, RR > 1 in every case). This was also seen in the outcomes of neonates in terms of perinatal death, stillbirth, neonatal death, congenital malformations, low gestation for age (LGA), low birth weight (LBW), jaundice. Here also the differences between GDM and non-GDM case were statistically significant (P < 0.0001, RR > 1 in every case) [Table 1]. In terms of H/O previous birth complication, again in the category of stillbirths and perinatal deaths both in GDM and non-GDM cases, the differences were statistically significant (P < 0.0001). However, in neonatal deaths, it was not significant in both GDM and non-GDM category (P > 0.05) [Table 2] As the blood sugar level rose above 120 mg/dl, perinatal mortality rose significantly as compared to previous perinatal loss (P < 0.0001). This increased Table 1 : Maternal and fetal outoomes of gestational diabetes mellitus and nongestational diabetes mellitus pregnant women Outcomes GDM cases (n=7641) N (%) Non-GDM cases (n=8000) N (%) p-value RR 95% CI Stillbirth 247 (3.2) 102 (1.3) 2.53 2.0-3.1 <0.44 Neonatal death 128 (1.7) 56 (0.7) 2.39 1.75-3.27 <0.0001 Perinatal death 375 (4.9) 158 (1.97) 2.48 2.0-2.9 <0.0001 Congenital malformation 382 (5) 82 (1.03) 4.87 3.8-6.1 <0.0001 Cesarean section 2242 (29.3) 1814 (22.67) 1.21 1.2-1.3 <0.0001 PBU Care 234 (3.06) 85 (1.06) 2.88 2.25-3.68 <0.0001 LGA 684 (9) 67 (.83) 10.6 8.3-13.7 <0.0001 LBW 863 (11.3) 758 (9.4) 1.19 1.1-1.3 <0.0002 PIH 1.83 686 (9) 483 (6) 1.6-2.0 <0.0001 Jaundice 4.76 382 (5) 84 (1) 3.7-6.0 <0.0001 Family history of DM 1372 (17.9) 546 (6.8) 2.62 2.3-2.8 <0.0001 APH/PPH 64 (.0.84) 26 (0.32) 2.57 1.6-4.0 <0.0001 APH : Antepartum hemorrhage, PPH : Postpartum hemorrhage; PIH : Pregnancy-Induced hypertension; LBW: Low birth weight; LGA: Low gestaion for age; PBU: Premature baby unit; OR : Odds ratio, RR : Relative risk; DM : Diabetes mellitus; GDM : Ges : Gestational diabetes mellitus Table 2 : Fetal outoomes in gestational diabetes mellitus versus nongestational diabetes mellitus and its relationship with history of previous birth complications GDM absent GDM cases Previous fetal loss Previous fetal loss Outcomes in p- value p- value (n=8000) neonate (n=7641) present present N (%) N (%) N (%) N (%) Stillbirth 247 (3.2) 916 (12) <0.0001 102 (1.2) 212 (2.6) <0.0001 Neonatal death 128 (1.7) 156 (2) <0.09 56 (0.7) 62 (9.8) <0.5 Perinatal death 375 (4.9) 1072 (14) <0.0001 158 (1.9) 274 (3.4) <0.0001 GDM : Gestational diabetes mellitus

35. Table 3 : Perinatal mortality as a function of blood sugar (mg/dl) vbalue and its comparison with a history of previous perinatal loss Blood gugar Perinatal mortality p-value Samples tested History of previous levels (mg/dl) present N (%) (n=57,018 perinatal mortality N (%) - - <100 n1=12,560 776 (2.4) 768 (2.5) 100-119 n2=31,075 <0.0001 137 (2.4) 214 (3.7) 120-139 n3= 5742 <0.0001 137 (3.5) 417 (10) 140-159 n4=3915 <0.0001 160-179 65 (4.4) 176 (12.1) n5=1451 <0.0001 180-199 54 (5.7) 168 (17.8) n6 = 940 <0.0001 119 (8.9) 311 (23.2) n7=1335 ‡ 200 <0.0001 The most important finding in our study was that as blood sugar levels rose above 120 mg/dl, there was significant perinatal mortality compared to previous perinatal loss (P <0.0001). This perinatal loss increased significantly from (5.7% to 8.9%), when blood sugar levels was‡ 199 mg/dl. This finding was also unique in contrast to many related [19-26] studies. It has been seen that the values of oral glucose tolerance test in the middle phase of pregnancy and [20] antenatal random glycemia can to some extent also predict PIH, preterm births, or stillbirths. DISCUSSION DISCUSSION DM is increasing worldwide and this rise is more prevalent in developing countries such as India, which is going to become the future "Diabetic-Capital," for which GDM is thought be a real contributor[12]. This emphasizes the importance of prevalence studies in India in pregnant women in order to reveal the exact prevalence of GDM. [12] Hence, GDM is emerging as a rising public health problem in pregnant women in India as many studies have indicated. [5,12-15] indicated. [5,12-15] DM is increasing worldwide and this rise is more prevalent in developing countries such as India, which is going to become the future "Diabetic-Capital," for which GDM is thought be a real contributor[12]. This emphasizes the importance of prevalence studies in India in pregnant women in order to reveal the exact prevalence of GDM. [12] Hence, GDM is emerging as a rising public health problem in pregnant women in India as many studies have 40 8 9 10 35.9 % of GDM Cases with Blood Sugar levels BS Controlled (in %) 35 8.9 BS Uncontrolled (in %) 30 Relative Risk 25 2 3 4 5 6 7 22.6 20 5.7 15.6 15 4.4 10 3.5 9.3 7.5 5 5.2 5.1 24 24 3.3 2.7 1.8 1.1 0.8 0 LGA PBU care Neonatyal death PIH Still birth 0 1 LBW Insulin Use Perinatal death Jaundice APH/PPH Family H/O DM Cesarean S 100-119 120-139 140-159 160-179 180-199 ‡ 200 Maternal & Neonatal Outoomes Figure 2 : Maternal and perinatal outcomes (in %) in gestations diabetes mellitus cases in relation to the Figure 2 : Maternal and perinatal outcomes (in %) in gestations diabetes mellitus cases in relation to the Figure 1 : Perinatal mortality (%) in gestational diabetes mellitus cases in relation to the Figure 1 : Perinatal mortality (%) in gestational diabetes mellitus cases in relation to the maternal blood sugar levels controlled by treatment (in g/dl). maternal blood sugar levels controlled by treatment (in g/dl). maternal blood sugar levels (in g/dl) maternal blood sugar levels (in g/dl) Jain, et al : Role of management of blood sugar in improving outcomes in GDM cases Table 4 : Post follow-up complications of gestational diabetes diagnosed in controlled and uncontrolled blood sugar after treatment Maternal and RR p-value BS-controlled (<140mg%) BS-uncontrolled (>140 mg%) 95% CI neonatal outcomes (n=4589) N (%) (n=454) N (%) 0.42 2.0-3.1 <0.0023 Stillbirth 64 (1.4) 15 (3.3) 0.04 30.28-0.98 <0.043 Neonatal death 37 (0.8) 8 (1.8) 0.43 0.28-0.68 <0.0002 Perinatal death 101 (2.19) 23 (5.1) 0.93 0.60-1.4 (<0.73 Congenital malformation 206 (4.5) 22 (4.8) 0.67 0.58-0.76 <0.0001 Cesarean section 1101 (24.0) 163 (35.9) 0.22 0.11-0.44 <0.0001 PBU Care 27 (0.59) 12 (2.75) 0.087 0.054-0.14 <0.0001 LGA 30 (.65) 34 (7.5) 0.57 0.46-0.73 <0.0001 LBW 413 (8.9) 71 (15.6) 0.32 0.23-0.45 <0.0001 PIH 137 (2.98) 42 (9.3) 0.11 0.062-0.18 <0.0001 Jaundice 26 (0.56) 24 (5.2) 0.34 0.28-0.41 <0.0001 Family history of DM 357 (7.7) 103 (22.6) 0.27 0.087-0.85 <0.025 APH/PPH 11 (0.23) 4 (0.88) 5.89 2.4-14.1 <0.0001 Insulin use 298 (6.4) 5 (1.1) APH : Antepartum hemorrhage, PPH : Postpartum hemorrhage; PIH : Pregnancy-Induced hypertension; LBW: Low birth weight; LGA: Low gestation for age; PBU: Prematurebaby unit; BS : Blood Sugar; OR: Odds ratio; RR: Relative risk; DM: Diabetes mellitus CONCLUSION Maternal and fetal outcomes in GDM cases are poor. Perinatal and maternal outcomes in GDM cases are also signficantly related to control or blood sugar levels. Therefore, blood sugar levels appear to be an important possible indicator of maternal and perinatal morbidity and mortality in Indian GDM cases. However, there is a need to unify diagnostic criteria in practices throughout the Indian subcontinent for a better validation of results from this study as well as other GDM studies conducted in India. th Presented at 7 World Congress of Diabetes DIABETESINDIA 2017 Hotel Pullman & Novotel, New Delhi, India.