Gestational diabetes GP Obstetric Shared Care Program Accreditation Seminars Shantha Joseph Endocrinologist Obstetric physician Sothern Adelaide Local Health Network

Objectives Overview of gestational diabetes Diagnostic criteria Recommendations for management Case discussions

GDM glucose intolerance of variable severity with onset or first recognition during pregnancy. The diagnosis of GDM includes those women with previously undiagnosed abnormalities of glucose tolerance, as well as women with glucose abnormalities related to the pregnancy alone. A definitive diagnosis of non‐gestational diabetes cannot be made until the post partum period

Gestational Diabetes Mellitus (GDM) Most frequent metabolic complication of pregnancy Gestational diabetes is generally defined as diabetes with initial onset or recognition during pregnancy Accounts for 90% of diabetes in pregnancy Affects ~7% of all pregnancies (range 1-14%) Highest in ethnic groups with high frequencies of type 2 diabetes (Aboriginal, Asian, and Pacific Island ancestry) independent of changes in definition,the prevalence of gestational diabetes is increasing

Changes in maternal glucose and insulin sensitivity in pregnancy Pregnancy results in profound changes in maternal metabolism During normal pregnancy there is a major change in insulin sensitivity marked fall in insulin sensitivity late in pregnancy, seen by all investigators 50–70% reduction in insulin sensitivity in women with gestational diabetes compared with controls In response to the insulin resistance,insulin secretion is increased and the net change in glucose for the majority of women increase is relatively small, Plasma glucose declines with pregnancy may reflect both dilutional effects and increased use by the foeto- placental unit

Main driver- TNF alpha discuss- adiposity- survival edge for human baby

the main biological difference between women with gestational diabetes and others is a failure of insulin secretion to rise in response to the physiological insulin resistance of pregnancy ? Underlying genetic factors Environmental co-factors failure of beta cell to produce increased insulin in response to the increased resistance- various causes several groups have examined genes associated with type 2 diabetes (almost all of which affect insulin secretion rather than insulin sensitivity12) and found that polymorphisms associated with type 2 diabetes may also be present in women with gestational diabetes.13 While of mechanistic interest it should be noted that currently known genetic variation accounts for a very small part of the variance of type 2 diabetes risk12 and so, at current levels of knowledge, may contribute only modestly to prediction of gestational diabetes risk

Consequences of GDM Fetal Morbidity Maternal Morbidity Hypertension Preeclampsia Increased likelihood of C-section Development of diabetes after pregnancy Fetal Morbidity Macrosomia (excessive birth weight) Neonatal hypoglycemia Polycythemia Increased perinatal mortality Congenital malformation Hyperbilirubinemia Respiratory distress syndrome Hypocalcemia

Diagnostic criteria and recommendations for management Review of literature

Objective: to clarify the risks of adverse outcomes associated with various degrees of maternal glucose intolerance less severe than that in overt diabetes mellitus 23,316 pregnant women without overt diabetes 15 centers in 9 countries over 6 years (July 2000 – April 2006)

Protocol Limitations No universal protocol Impossible to compare different studies of GDM ? true prevalence of GDM ? risks associated with maternal hyperglycemia

Consensus Needed for New Criteria International Association of Diabetes in Pregnancy Study Groups (IADPSG) 2008 conference to review HAPO and related studies data Establish new diagnostic criteria for GDM

SAPPG OGTT May be performed at any time during pregnancy if symptoms and signs of abnormal glucose tolerance e.g. excess thirst; polyuria, polyhydramnios, macrosomia Consider an early test (around 12-16 weeks of gestation) for women with a past history of gestational diabetes if a recent OGTT has not been performed Women with known glucose intolerance outside pregnancy may be considered to have gestational diabetes from the time of conception and therefore a repeat OGTT is not required

Universal screening at 26-28 weeks GA – OGCT If positive proceed to OGTT

ADIPS 2002 High risk factors: Glycosuria; Age over 30 years; Obesity; Family history of diabetes; Past history of GDM or glucose intolerance; Previous adverse pregnancy outcome; and Belonging to an ethnic group with a high risk for GDM

ADIPS 2013 Recommendations for early testing for GDM for women with high risk • Previous GDM • Previously elevated blood glucose level • Ethnicity: Asian, Indian, Aboriginal, Torres Strait Islander, Pacific Islander, Maori, Middle Eastern, non‐white African • Maternal age ≥40 years • Family history DM (1st degree relative with diabetes or a sister with GDM) • Obesity, especially if BMI > 35 kg/m2 • Previous macrosomia (baby with birth weight > 4500 g or > 90th centile) • Polycystic ovarian syndrome • Medications: corticosteroids, antipsychotics The diagnosis of GDM will therefore include those women with previously undiagnosed abnormalities of glucose tolerance, as well as women with glucose abnormalities related to the pregnancy alone. A definitive diagnosis of non‐gestational diabetes cannot be made until the post partum period. ADIPS does not currently recommend the use of the term “Overt Diabetes” (as proposed by IADPSG) to describe marked hyperglycaemia (consistent with diabetes if detected outside pregnancy) first detected in pregnancy. However, clinical judgement should be used to detect marked hyperglycaemia especially in early pregnancy (first visit). These women are at higher risk of major pregnancy complications and require urgent attention, including evaluation for other complications of the undiagnosed diabetes. Page 2

ADIPS 2013 All women not known to have GDM, should have a 75g OGTT at 24–28 weeks gestation A diagnosis of GDM is made if one or more of the following glucose levels are elevated; Fasting glucose ≥ 5.1mmol/L 1‐hr glucose ≥ 10.0mmol/L 2‐hr glucose ≥ 8.5mmol/L

How does this compare with the existing protocol Current protocol based on ADIPS 2002 New ADIPS recommendations- not accepted yet Universal screening at 26-28 weeks with GCT- 50 gm glucose- ≥ 7.8 mmol/L If positive – 75gm OGTT High risk – 75 gm OGTT at time of contact with health system All others OGTT at 24-28 weeks OGTT Diagnostic criteria Fasting glucose ≥ 5.5mmol/L 2‐hr glucose ≥ 7.8 mmol/L (SAPPG- 8.0 mmol/l) Fasting glucose ≥ 5.1mmol/L 2‐hr glucose ≥ 8.5mmol/L Therapeutic criteria fasting glucose level <5.5 mmol/L • 2 hour glucose level <7.0 mmol/L Fasting glucose ≤ 5.0mmol/L 2 hour glucose ≤ 6.7mmol/L

Current practice in SA

Diagnostic criteria for Gestational Diabetes SAPPG-Based on ADIPS criteria- 2002 Universal screening plus high risk patients screened earlier The recommended screening test for GDM- OGCT performed at 26-28 weeks' gestation and positive results are: 1 hour venous plasma glucose level 7.8 mmol/L after a 50 g glucose load (morning, non-fasting); Confirmation of diagnosis after a positive screening test:OGTT a 75 g oral glucose tolerance test (fasting) with a venous plasma glucose level at 0 hours of 5.5 mmol/L and/or at 2 hours of 8.0 mmol/L.

Post diagnosis Review by Diabetes nurse educator – group session with DNE and dietician BGL monitoring, provision of glucometer and forms for NDSS-for supplies BGL monitoring- 4 times a day Fasting, 2 hours after BF, lunch and dinner Targets- fasting <5.5 mmol/L and post meal<7 mmol/L Review in Obs med clinic- usually 1-2 visits unless issues present Phone contact with DNE

Imaging studies Ultrasound for fetal size at least once at 36 to 37 wk; more frequently if macrosomia suspected Fetal echo if required Antenatal testing Routine blood pressure and urine protein monitoring

Non-pharm Rx Regular moderate exercise Dietary modifications aimed at glycemic control: low-fat, high-fiber diet; avoid sugar and concentrated sweets; and eat small, frequent meals. Nutrition counseling for diet that adequately meets the needs of pregnancy but restricts carbohydrates to 35% to 40% of daily calories. For women with a body mass index >30, restrict calories to 25 kcal/kg actual weight per day.

Pharmacologic Rx Start if BSLs > cutoff on at least 2 occasions during same time period of the day Clinical judgement re-educate – DNE review If fasting values are elevated, use NPH at bedtime If postprandial values are elevated, use ultra rapid-acting insulin before meals Metformin in select patients with initial dose of 0.2 U/kg protaphane NR- with initial dose 1.5 U/10 g carbohydrate at breakfast and 1 U/10 g carbohydrate at lunch and dinner

Post-partum Glucose profile on day 3-4 post partum All women with gestational diabetes should have a glucose tolerance test at 6-12 weeks post partum The Gestational Diabetes Recall Register should be offered (if the woman has not already been recruited to this) to facilitate long-term follow-up

cases

Ms BY 28 year old recently migrated from Canada BMI-24 Non smoker, nil medical issues Maternal grandmother had late onset T2DM

When to test? Issues of concern Best place of care Pros and cons Ongoing nausea- unable to tolerate GCT Alternative diagnostic tests include capillary blood glucose monitoring (fasting and postprandial over a week and review Alternative diagnostic tests Alternative diagnostic tests include capillary blood glucose monitoring (fasting and postprandial – see below) over a number of days, particularly if there has been previous intolerance of glucose loading

Alternative Approaches Jelly beans for GDM screening (AJOG 1999;181:1154–1157) 50 g glucose beverage is intensely sweet 15-20% of patients experience nausea and vomiting (voids test) 28 Brach’s No. 110 jelly beans = 50 g glucose Poor sensitivity compared to beverage (40 vs. 80%, respectively)

HAPO Hb A1c-not a useful alternative to OGTT ADIPS 2013- measurement of HbA1c - level of ≥ 48mmol/mol (6.5%) is diagnostic of GDM and very likely represents previous undiagnosed type 2 diabetes Can be considered- In areas where the rate of undiagnosed type 2 diabetes is thought to be high, In remote areas where the performance of a GTT may be logistically difficult,

Ms AZ 42 year old primi, Caucasian History of PCOS Obese, non-smoker Family history of DM- brother and father- T2DM

When to test? Issues of concern Best place of care Pros and cons GCT- 8.5 mmol/L OGTT- F-5.9 mmol/L 2h PP- 9.1 mmol/L BSL monitoring Raised BSL in fasting column >2 x in a fortnight Ongoing hyperglycemia- Rx options Needle phobic- teary 16 weeks GA- options

Metformin Metformin versus Insulin for the Treatment of Gestational Diabetes MiG Trial NEJM 2008 showed that use of metformin gives comparable outcomes to insulin in the management of women with gestational diabetes. Women treated with metformin had offspring with less severe neonatal hypoglycaemia. They gained less weight during pregnancy and lost more weight after delivery. Women preferred treatment with metformin. Follow up of the offspring to date has shown no difference between those whose mothers were treated with insulin and those whose mothers were treated with metformin

Summary GDM glucose intolerance of variable severity with onset or first recognition during pregnancy. Important to recognise as maternal and fetal consequences can be dangerous SAPPG in line with ADIPS 2002- no change to criteria for diagnosis or management till further research- which is being planned Alternative approaches for diagnosis- BSL monitoring x 1 week HbA1C Alternative approaches for Rx Metformin vs insulin Post partum- critical to do OGTT

Thank you