Presentation on theme: "Bashir Taha Salih MD Germany, FRCOG UK Consultant & Chief Obstetric Medicine Corniche Hospital Abu Dhabi Kuwait April 27 th 2014 Gestational Diabetes Gestational."— Presentation transcript:
Bashir Taha Salih MD Germany, FRCOG UK Consultant & Chief Obstetric Medicine Corniche Hospital Abu Dhabi Kuwait April 27 th 2014 Gestational Diabetes Gestational Diabetes
Contents Introduction Physiology What’s new in GDM ? In Screening In Management Conclusion
Introduction GDM increases the risk of complications for both mother and fetus during pregnancy, childbirth and beyond – increased risk of Type 2 diabetes International Association of Diabetes and Pregnancy Study Groups, Diabetes Care March 2010 vol. 33 no. 3 676-682
Introduction Current evidence suggests early detection and management of gestational diabetes: ◦ Improves outcomes for both mother and baby ◦ More cost effective by preventing the complications International Association of Diabetes and Pregnancy Study Groups, Diabetes Care March 2010 vol. 33 no. 3 676-682 National Collaborating Centre for Women's and Children's Health. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period. London, U.K., RCOG Press, 2008
Definition Gestational Diabetes Mellitus (GDM) is one of the most common medical disorders in pregnancy and is defined as “any degree of glucose intolerance with onset or first recognition during pregnancy” American Diabetes Association. Diagnosis and classification of diabetes mellitus (Position Statement). Diabetes Care 2009;32(Suppl. 1):S62–S67
Diabetes in pregnancy and risk of complications Pre-existing diabetes in pregnancy is associated with high rates of complications: ◦ Fetal/neonatal Congenital malformations Perinatal mortality Excess fetal growth Traumatic delivery Neonatal hypoglycaemia Hyperbilirubinaemia Diabetic fetopathy ◦ Maternal Pregnancy-induced hypertension/pre- eclampsia Polyhydramnios/large for gestational age Operative delivery Dunne et al. Diabetes Care 2009;32:1205–6
Diabetes in pregnancy and risk of complications Confidential Enquiry into Maternal and Child Health (CEMACH): Pregnancy in Women with Type 1 and Type 2 Diabetes in 2002–03, England, Wales and Northern Ireland. London: CEMACH; 2005 OutcomePregnant women with type 1 or type 2 diabetes National data (background population) Rate ratio Pre-term delivery37%7.3%5 Birth weight ≥90th percentile 52%10%5.2 Shoulder dystocia7.9%3%2.6 Erb’s palsy4.5/10000.42/100011 Neonatal unit admission 56%10%5.6 Term admission for special care 33%10%3.3
Blood glucose control is linked with outcomes in diabetic pregnancy Diabetes Control and Complications Trial. Am J Obstet Gynecol 1996;174(4):1343–53
Glycaemic thresholds for prevention of diabetic fetopathy complications? Langer. Diabetes Reviews 1996;4:2–10 LGA, large for gestational age Complication Mean blood glucose mmol/Lmg/dL Spontaneous abortion <8.9<160 Congenital anomalies <7.8<140 Stillborn<6.1<110 Lung maturation<6.1<110 Metabolic complications <6.1<110 Macrosomia/LGA<5.6<100
Physiology of Insulin resistance during pregnancy Physiology of Insulin resistance during pregnancy Increased insulin resistance is : the decreased biological response to given concentration of insulin at the target tissues, such as liver, muscle, or adipose tissue. Insulin resistance is implicated in (T2D) & (GDM) pathophysiology Strongly linked with metabolic syndrome and associated with increased risk of developing cardiovascular diseases (CVD) Over the course of normal pregnancy, insulin sensitivity decreases by 50 %–60 %. Level of insulin resistance achieved in late pregnancy comparable to the level observed in patients with impaired glucose tolerance (IGT) or newly diagnosed with T2D.
Physiology of Insulin resistance during pregnancy Physiology of Insulin resistance during pregnancy GDM results from an imbalance between increased insulin resistance and the capacity of pancreatic β -cells to face the demand increasing through pregnancy. Some of the mechanisms raising insulin resistance are likely the same during and outside of pregnancy, while other pathways are probably specific to gestational physiologic adaptations and hormonal regulation
Physiology of Insulin resistance during pregnancy Physiology of Insulin resistance during pregnancy Cytokines and Adipokines The adipose tissue is now recognized as an endocrine organ that is capable of producing a significant amount of cytokines and hormones, often called adipokines. In non-pregnant populations, many cytokines and Adipokines, including TNF α, Leptin, and Adiponectin, have been suspected to contribute to insulin resistance pathways. Interestingly, the placenta seems also to be a significant source of ‘classic’ Adipokines such as Leptin and of proinflammatory cytokines (TNF α, Interleukins, etc).
Physiology of Insulin resistance during pregnancy Physiology of Insulin resistance during pregnancy They found that TNF α showed the strongest correlation with insulin sensitivity, both in early and late pregnancy and that most of the placental production of TNF α was released on the maternal side towards the maternal circulation. None of the pregnancy-related hormones were significantly associated with insulin sensitivity, but Leptin was the second best predictor among the circulating protein assessed in this specific sample of women
Physiology of Insulin resistance during pregnancy Physiology of Insulin resistance during pregnancy LEPTIN: Initially described as an adipokine responsible for energy balance Leptin level increases early in pregnancy, reaches a peak in the second trimester, remains stable in late pregnancy, and falls within hours after delivery.Suggesting that the placenta contributes to a significant portion of circulating levels during pregnancy. In GDM women, expression of LEP has been shown to be higher in adipose tissue and in the placenta. Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France Hivert Published online: 11 January 2013
Maternal and Early Determinants of Insulin Resistance in Offspring Maternal Obesity was associated with insulin resistance in young adults. At birth, higher maternal (BMI) is associated with higher cord blood insulinemia, even in women with normal glucose tolerance or independently of maternal glycemia It is also possible that obese women that are ‘normoglycemic’ have ‘relative’ hyperglycemia leading to some degree of fetal hyperinsulinemia and its consequences. Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France Hivert Published online: 11 January 2013
Maternal and Early Determinants of Insulin Resistance in Offspring Birth Weight associated with increased risk of insulin resistance at both ends of the spectrum: being small for gestational age (SGA) or large for gestational age (LGA) was associated with higher HOMA-IR compared with children who were appropriate for gestational age (AGA) at birth Correlation between SGA and increase insulin resistance was confirmed in numerous studies, including young adults that were assessed by the intravenous minimal model method or the euglycemic hyperinsulinemic clamps suggested that abnormal adipose tissue metabolism is part of the pathophysiological processes linking low birth weight to insulin resistance. Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France Hivert Published online: 11 January 2013
In Summary : One of the determinants of insulin resistance in normal pregnancy and GDM is placenta which is capable of secreting many cytokines and hormones, classically considered as adipocytes. More specifically, it appears that leptin and TNF α could be implicated in gestational insulin resistance and GDM pathophysiology. Overall, pregnancy-related increase in insulin resistance helps to reveal a defect in insulin action and/or insulin secretion compensatory capacity. For this reason, pregnancy is often considered ‘a window’ to identify women at risk of developing T2D in the future and an opportunity for prevention. In addition, the maternal metabolic milieu was also identified as a key determinant of later insulin resistance in offspring, a phenomenon often described as ‘fetal programming’ Maternal/Fetal Determinants of Insulin Resistance in Women During Pregnancy and in Offspring Over Life by Marilyn Lacroix & Eralda Kina & Marie-France Hivert Published online: 11 January 2013
Screening of Gestational Diabetes Who to Screen? Screen all pregnant women!
Universal VS Selective Screening At present, both methods are employed in reputable centers In UAE as the prevalence of diabetes is high, universal screening is recommended Selective screening has a sensitivity of 63% and a specificity of 56% In other words, 37%–50% of women with GDM may go undiagnosed using this approach
Prevalence of Diabetes Top Ten Countries/Territories Prevalence of Diabetes Top Ten Countries/Territories Countries/TerritoriesPrevalence (%) Kiribati25.7 Marshal Islands22.7 Kuwait21.1 Nauru20.7 Lebanon20.2 Qatar20.2 Saudi Arabia20.0 Bahrain19.9 Tuvalu19.5 United Arab Emirates19.2 http://www.idf.org/sites/default/files/da5/prevalence IDF Diabetes Atlas 2011
When to Screen ? At booking Earlier the screen the better the outcome First prenatal visit: Test for overt diabetes At 24-28 weeks IADSPG
GDM Diagnosis Controversy GDM Diagnosis Controversy Difference in 6 major criteria for GDM diagnosis? WHO (World) EASD (European) ADA (American) CDA (Canadian) ADIPS (Australasian) NZSSD (New Zealand) Agarwal et al. Diabetic Medicine 2005
Hyperglycemia and Adverse Pregnancy Outcome Study
HAPO Trial Hyperglycemia & adverse pregnancy outcome Randomized Clinical Trial 15 world centers 25,000 women Six years Aims to correlate various levels of glucose to outcome
The HAPO Study The HAPO Study was designed to clarify unanswered questions on associations of maternal glycaemia, less severe than overt diabetes mellitus, with risks of adverse pregnancy outcome.
The HAPO Study Primary outcomes in the blinded HAPO cohort Birth weight >90th percentile Primary cesarean section delivery Clinically defined neonatal hypoglycemia Cord C-peptide >90th percentile
The HAPO Study Secondary outcomes Pre-eclampsia Preterm delivery Shoulder dystocia/birth injury Hyperbilirubinemia Intensive neonatal care
The HAPO Study Frequency of primary outcomes across the Glucose categories The HAPO Study Cooperative Research Group. N Engl J Med
The HAPO Study Results indicate strong associations of maternal glucose levels below those diagnostic of diabetes with adverse pregnancy outcomes.
International Association of Diabetes and Pregnancy Study Groups (IADPSG) Formed in 1998 as an umbrella organization to facilitate collaboration between the various regional and national groups that have a primary or significant focus on diabetes and pregnancy.
Objectives of IADPSG Foster an international approach to enhancing the quality of care Facilitating research Advancing education in the field of diabetes in pregnancy.
International Council Diabetes in Pregnancy Groups European Japanese Australasian Canadian USA India ADA Diabetes Care March 2010
UNIVERSAL SCREENING FOR DIABETES MELLITUS IN PREGNANCY At booking:- FBS+ HbA1C + RBS If :FBS < 5.1 mmol/l HbA1c < 6.5% RBS < 11.1mmol/l If FBS >5.1mmol/l And < 7.0mmol/l 75 gm OGTT at 24-28 wks Threshold : FBS: 5.1mmol/l 1 Hr : 10.0 mmol/l 2 Hrs : 8.5 mmol/l FBS >7.0 mmol/l Or HbA1c > 6.5% or RBS >11.1mmol/l Overt diabetes No further test GDM: 1or more values ≥ threshold Normal diet + BSS HbA1c 4 wkly Normal Low risk GDM, no further test Dietician (medical nutrition Therapy) CDC/ DE (Insulin+Met) Abnormal
IADPSG Glucose MeasuredConsensus threshold FBS≥7.0 mmol/l (126 mg/dl Random plasma glucose≥11.1 mmol/l (200 mg/dl) HBA1C≥6.5% If results indicate overt diabetes Treatment and follow-up as for pre-existing diabetes
IADPSG If results not diagnostic of overt diabetes and Fasting plasma glucose ≥ 5.1 mmol/L (92 mg/dl) but < 7.0mmol/l(126 mg/dl) “Treat as Gestational Diabetes (IADPSG)”
The Glucose Tolerance Test The Glucose Tolerance Test
Timing of OGTT At 24-28 weeks of pregnancy as per IADPSG criteria. Insufficient data to recommend OGTT to diagnose Overt diabetes prior to 24-28 weeks.
Diagnosis of GDM in Pregnancy Threshold Value Glucose measure Mg/dlMmol ≥ Threshold(%) Of population FBG925.18.3 1 hr OGTT1801014.0 2hr OGTT1538.516.1 GDM =1 or more values ≥ threshold
IADPSG- Detection & Diagnosis of Hyperglycemia Disorders in Pregnancy First Antenatal Visit: Test for overt DM FBS,HbA1C or RBS in all women Results indicate overt DM Treatment & follow up as for pre-existing DM Results not diagnostic of overt DM FBS 5.1-6.9mmol/l = GDM Others: test for GDM 24-28 weeks gestation with 75g OGTT
IADPSG - Adoption Of Criteria AcceptedRejectedIn Progress / Pending ADAACOG (recently accepted) WHO JapanSpainUK IndiaNIHNZ Brazil Italy Germany ADIPS(Aust) Corniche Abu Dhabi
UPSTF All women should be screened for gestational diabetes at 24 weeks of pregnancy, even if they have no symptoms, according to new federal recommendations. The B-level recommendation from the U.S. Preventive Services Task Force (USPSTF), published in the Annals of Internal Medicine, aligns with that of several other medical organizations, including the B-level recommendationAnnals of Internal Medicine American Association of Clinical Endocrinologists,American Association of Clinical Endocrinologists American Diabetes Association (ADA), and the American College of Obstetricians and Gynecologists (ACOG).
Audit of Universal Screening of Diabetes in Pregnancy using IADSP in Corniche Hospital
Obstetric Medicine in Corniche Hospital Corniche Hospital is a 235 bedded largest maternity tertiary hospital in the UAE with 8,000 to 10,000 deliveries per annum. The Obstetric medicine department was established in 1994. Provides daily inpatient and out patient consultation for women with medical problems predating, during or after pregnancy. The only unit outside UK accredited to train Obstetrians in Maternal medicine by the RCOG Provides 24/7 on call service.
Frequency of Primary Outcomes across the Glucose Categories The HAPO Study Cooperative Research Group. N Engl J Med
Treatment of GDM Life style/ Medical Nutrition Therapy (MNT) Oral hypoglycaemic (Glyburide, Metformin) Insulin
Management of gestational diabetes mellitus American Diabetes Association. Diabetes Care 2004;27:s88–s90
Self-monitoring of Blood Glucose (SMBG) Insulin Pump
Treatment Goals HbA1c The long-term average glucose level Below 6 % FPG The Fasting glucose level <92 mg/dl (5.1 mmol/L) PPG The postprandial glucose level< 120 mg/dl (6.7mmol/L)
Recommended glycaemic control targets for women with GDM ADA. Diabetes Care 2010;33(Suppl. 1):S11–61 ADA. Diabetes Care 2004;27(Suppl. 1):S88–90 GDM, gestational diabetes mellitus Recommended that women monitor pre- and 1-hour post- meals and at bedtime; occasional sample during night Preprandial glucose<95 mg/dL (5.3 mmol/L) 1-hour postprandial glucose<140 mg/dL (7.8 mmol/L) 2-hour postprandial glucose120 mg/dL (6.7 mmol/L)
Oral Hypoglycaemic Agents Sulphonylureas Glyburide 404 women 11- 33 wks Insulin vs Glyburide Similar Perinatal Outcome Similar Glycaemic Outcome Save in pregnancy Langer O, et al. N Engl J Med October 19, 2000:343:1134-8
Oral Hypoglycemic Agents Oral Hypoglycemic Agents Biguanides ( Metformin) insulin sensitiser, no stimulation FDA Cat B1 drug Commonly used in PCOS to treat insulin resistance and normalize reproductive function Non-teratogeneic ? Reduce first trimester miscarriage 10X reduce gestational diabetes Reece, Curr Opin Endocrinol Diabetes, 2006 Glueck, Fertil Steril 2002 Hague, BMJ, 2003 Glueck, Human Reprod, 2004
History of Metformin Extracted from a plant Galega Officinalis ( Professor weed, French Lilac) First synthesised in 1922 at Trinity College, Dublin, Ireland Oral anti-diabetic agent 35 years later by a French physician, Dr Jean Sterne as “Glucophage”- glucose eater
Known Effects of Metformin Known Effects of Metformin Improves insulin sensitivity Reduces hepatic gluconeogenesis Increases peripheral glucose uptake Reduces fasting serum insulin by 40% Weight reduction 5.8%
Safety of Metformin in pregnancy Safety of Metformin in pregnancy Crosses the placenta, but no evidence of adverse fetal effects FDA class B1 Coetzee et al S Afr Med J 1980; 58: 795-802 Coetzee et al S Afr Med J 1984;65:241-5 Glueck CJ et al. Fertil Steril 2001;75:46-52 Glueck CJ et al Hum Reprod 2002;17:2858-2864 Gutzin SJ et al Can J Clin Pharmacol 2003;10:179-183 Glueck CJ et al Hum Reprod 2004;19:1323-1330 Vanky E et al Hum Reprod 2004;19:1734-1740 Gilbert C et al Fertil Steril 2006;86:658-663 Rowan JA et al N Engl J Med 2008;358:2003-15 Balani J et al Diab Med 2009 Aug 26(8) 798-802 Goh JEL et al Diab Med 28, 1082-1087 (Sept 2011) Jakubowicz et al The journal of clin endo & metab 87(2)524-529
Metformin in Gestational Diabetes (MIG) Trial Perinatal morbidity was compared in the Metformin (n= 373) and insulin (n = 378) groups They concluded that perinatal complication rates are similar and Metformin was safe More women in the Metformin group than in the insulin group they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001) NICE Diabetes in Pregnancy Clinical Guidelines (63) 2008 Rowan JA, Hague WM et al N Eng J Med 2008 358: 2003-15
Pregnancy outcomes in women treated with metformin for gestational diabetes J BALANI, S HYER, A RODIN, A JOHNSON, H SHEHATA Department of Diabetes and Maternal Medicine Epsom and St Helier University Hospitals NHS Trust, Surrey, UK
Why use Metformin in Gestational Diabetes? Pregnancy is an insulin resistant state Metformin improves insulin sensitivity, especially in liver and muscle Reduces hepatic gluconeogenesis and improves peripheral glucose uptake Stimulates GLP-1 release Convenience of oral formulation
Outcome of Gestational Diabetes Mellitus Patients Treated with Metformin Dr Aleyzabathu Philp Dr Bashir Salih Dr Nageena Mahmood Dr Vijayamani Baichoo
Conclusion of Study Metformin alone or with small supplemental dose of insulin is effective treatment for GDM and is more acceptable to all ethnic groups of patients No increase in the congenital anomalies Reduction of symptomatic neonatal hypoglycaemia Decrease in Admission to NICU
Insulin Analogues Rapid Acting Lispro Aspart Both safe in pregnancy Gluisine (Apidra)? Long Acting Detemir/ Levemir (FDA classB) Glargine/ Lantus
Postpartum Management Postpartum Management Patients with gestational diabetes Stop hypoglycemic medication immediately after birth OGTT 6 weeks postnatally To start tablet folic acid and to attend preconception clinic when planning pregnancy for screening of diabetes Life-long screening for development of diabetes at least every 2-3 years
UK CEMACH report: pre-pregnancy preparation is still suboptimal Confidential Enquiry into Maternal and Child Health (CEMACH): Pregnancy in Women with Type 1 and Type 2 Diabetes in 2002–03, England, Wales and Northern Ireland. London: CEMACH; 2005 Pre-pregnancy Type 1 (n=2767) Type 2 (n=1041) Counselling documented 1056 (38.2%)258 (24.8%) Glycaemic test recorded 1108 (40.0%)306 (29.4%) Folic acid1187 (42.9%)306 (29.4%)
Preconception Care Counselling and Education Life style change Weight Reduction Regular Exercise HbA1c 6.5% preferable < 6% Folic Acid