Diabetes in Pregnancy

Dr Gill Spyer

Summary

• Prevalence and aetiology• Risks to mother• Risks to foetus• NICE guidelines• Management of acute presentations

A 33 year old woman presented to her optician in early pregnancy with sudden loss of vision in her left eye.

R Eye L Eye

• Diabetes was subsequently confirmed (HbA1c 7.2%)• She was also noted to be anaemic (haemoglobin

8.1grams per decilitre) and had impaired renal function (Creatinine 200micromols per litre, GFR 26mililitres per minute)

• Renal biopsy showed increased mesangial matrix, thickened basement membrane and fibrous crescents consistent with diabetic nephropathy

• What are the risks- To the mother?- To the fetus?

• What is the best course of management?- Treatment options- Termination of pregnancy?

Taken from S Germain and C Nelson Piercy. Lupus 15, 148-155, 2006.

Taken from N Kevin Krane Peritoneal dialysis and Haemodialysis in pregnancyHemodial Int. Vol. 5, 97–101, 2001

Retinopathy and pregnancy• Risk adverse outcome correlates with severity of disease at baseline.• Proliferative retinopathy associated with high risk of obstetric complications such as

hypertension (100% in one study) and unfavorable outcome (43%v13% with no retinopathy) including severe malformation and/or fetal death (20%).

• Progression during pregnancy-12% of women with no retinopathy at the start of pregnancy will develop minor

background retinopathy. Resolves post partum-29% moderate retinopathy at baseline went on to develop proliferative changes

during pregnancy. This was in contrast with those women who had minimal retinopathy at baseline where only 6.3% progressed to the proliferative category.

- 58% proliferative retinopathy significant progression and visual loss after treatment during pregnancy. Better outcome if identified and treated prior to pregnancy (26% progression in this group)• Fifty five per cent of those with a hypertensive disorder developed progression of

retinopathy as opposed to 25% of those that did not.

Management• Termination recommended but not an option for her• She received insulin, aspirin and antihypertensive agents

from 12 weeks gestation and urgent bilateral pan retinal photocoagulation.

• She commenced daily haemodialysis and weekly erythropoietin from 16 weeks.

• Fetal growth restriction led to delivery by Caesarean section at 30 weeks, a baby boy (1200g) subsequently did well.

• Postnatally the patient remained on insulin and antihypertensive treatment. She had not required further dialysis (creatinine 395micromols per litre at 6 week postnatal check) but was listed for renal replacement therapy pending renal transplant.

• Visual acuity remained poor and she underwent vitrectomy.

GDM5% pregnancies

T1/T2 diabetesMODY0.7%

?

Diabetes and pregnancy

Prevalence

• Pre existing diabetes complicates 0.7% of all pregnancies

• Increasing prevalence of type 2 diabetes compared with type 1 (45% in National Diabetes in pregnancy audit 2013)

• GDM, development of diabetes during pregnancy complicates around 5% pregnancies. Usually picked up on screening at 26-28 weeks. Aetiology is heterogenous. Incidence also rising

What are the risks?

Mother• Acceleration of

complications eg eye andrenal disease

• Risk of hypoglycaemia

• Pre-eclampsia• Obstetric

complications and c section

Foetus• Congenital

malformation• Macrosomia• Still birth and

neonatal death• Postpartum

hypoglycaemia, hyperbilirubinaemia etc

Fig 2 The risk of all congenital malformations is increased above the background population rate of 2%, even in women with type 1 diabetes with normal HbA1c concentrations.

Roy Taylor, and John M Davison BMJ 2007;334:742-745

Risk of fetal death and Hba1c

Infant death

Late stillbirth >28wk

Stillbirth>24 wk

Fetal death>20 wk

NICE ADA Avoid pregnancy

Risk factors for poor pregnancy outcome (CMACE 2007)

• Poor pregnancy preparation/unplanned pregnancy (no high dose folic acid etc)

• Suboptimal glycaemic control• Complications of diabetes (retinopathy,

nephropathy)• Fetal IUGR• Suboptimal maternity and diabetes care

(maternal and fetal surveillance and monitoring of diabetes complications)

What does NICE say?

• Take folic acid 5mg OD until 12 weeks (T1/T2)• Aim Hba1c<48mmol/mol and avoid pregnancy if

Hba1c>86mmol/mol (T1/T2). • Discontinue potentially harmful medication (ACE, statin,

OHA’s). Metformin OK, Isophane insulin and some analogues OK

• Start aspirin 75mg od from 12 weeks (T1/T2)• BG targets same for all. In this trust fpg <5.5 and pg<7.0

2 hours after eating (not NICE compliant)• BG 4-7 during labour and delivery

National Diabetes in Pregnancy Audit 2014 – how are we doing?

• 2537 women 46.7% T2• 41.9% taking folic acid (any dose) pre-pregnancy• 15.4%T1 35.8%T2 Hba1c<48 in 1st trimester• 9.7% Hba1c>86 1st trimester• 6% potentially harmful meds at conceptionOutcomes • 12.8 stillbirths/1000 births, 7.6 neonatal

deaths/1000 live births, 44.2 anomalies/1000 births• 34.3% LGA (46% T1; 23%T2), 14.3%>4Kg at birth

Conclusions NPID

• Women poorly prepared for pregnancy• No improvement in outcomes since CEMACH

in 2002/3

What are the acute presentations

• Hypoglycaemia (BM <4)• Hyperglycaemia (BM>11)• Ketosis (Ketones >1.5)

Hypoglycaemia - what are the issues

• Common in type 1 (45 % at least 1 severe hypo). Most common in the first trimester even though control tighter later on in pregnancy. 37% occur at night. May not be recognised.

• Risk factors include previous severe hypo, hypo unawareness

• Treat hypo as normal• Look for cause eg lipohypertrophy• Consider reducing insulin• Check patient has glucagon at home

Late gestation Hypo’s

• 3rd trimester hypo’s can indicate placental failure

• Treat hypo and look for cause• Consider reducing insulin• Refer urgently to obstetrics for foetal

assessment

A 33yo lady presents to ED with nausea and vomiting. She has type 1 diabetes and is 25 weeks pregnant. BM is 9

Ketones 6.5 pH 7.2 Bicarb 12

Diagnosis? EUGLYCAEMIC DKA

DKA in pregnancy

• 3 % diabetic pregnancies – usually but not always T1’s• Usually occurs in 2nd/3rd trimester• Can be precipitated by steroids & beta agonists• May present with lower blood glucose due to

exogenous correction doses insulin, food restriction and increased consumption by placenta and fetus (euglycaemic DKA)

• It is associated with high fetal mortality (10 -50%) don’t miss it!

Hyperglycaemia/acute illness in pregnancy

General principals of management- Discuss with woman - Women with longstanding diabetes

can have variable CBG control. They self-manage their diabetes and in many situations will often know the reason for hyperglycaemia and how to correct this.

- Assess clinically - Ensure that woman has taken her insulin, is not dehydrated, is not infected, and that she has eaten.

- Measure ketones -Labour ward has a ketone meter. Many women will have mild ketonuria after an overnight fast; this can be exacerbated by dehydration and will clear with a meal, oral fluids and standard insulin. Ketonaemia can occur in T2 and patients with GDM. Can occur with relatively “normal” BG levels

If ketonuria ≥3+ or blood ketonaemia > 3mmol/l

• Check for acidosis by measuring pH and serum bicarbonate on venous blood gas

• If bicarbonate <15mmol/l or venous pH <7.3 acknowledge emergency and follow Trust DKA management • If bicarbonate 15-20 mmol/l:

-Commence IV fluids. Use 0.9% sodium chloride, 1000mls in one hour

-Ensure insulin and food has been taken.-Woman might require an extra dose of quick acting insulin

• If bicarbonate >20 mmol/l follow advice below

If no ketonuria or blood ketones <3.0mmol/l

• Ask if woman knows reason for hyperglycaemia• Ensure they are not dehydrated – drink 200 mls sugar-

free fluid every hour until ketones clear.• They should take their insulin as usual and might

require extra quick acting insulin (up to 10% of total daily dose) added to this dose:

• Consider correction dose of insulin As a general rule we advise that 1 additional unit of quick acting insulin reduces CBG by 3mmol/l.

• Recheck CBG and ketones after 2- 4 hours.

• 31 yo lady T1 diabetes. 36+5/40 gestation admitted for iv steroids prior to IOL at 37+/40 for polyhyramnios and fetal macrosomia. BM 9.6

• What are the options?- Do nothing- Increase insulin – by how much?- Sliding scale?

Check blood glucose pre and 2 hours post prandial, nocte then every 4 hours overnight, or at least 4 hourly if not eating properly or unwell

Inform Diabetes team of admission ext 55525

Steroid Dexamethasone BetamethasoneBlood sugar monitoring 12 hours after each dose 24 hours after each dosePeak effect 6 Hours 12 hours

Day of admission Increased insulin by 20% at any meal Increase usual night long-acting within 6 hours of dose insulin dose by 20%

40% at any meal for next 12 hoursthereafter Increase usual night long-acting insulindose by 20%

2nd day Increase insulin by 20% at any meal Increase insulin by 40%, 40% and 20% until 24 hours post first dose. at each meal.

10% at night dose until 48 hours post first dose

Mixed insulin bd Increase usual insulin doses by Increase usual insulin doses byapproximately 30% for 24 hours approximately 30% for 48 hours

Additional 8 units short acting insulin if capillary glucose > 8 mmol/l.The patient may give extra doses of short acting insulin to control blood glucose if confident to do so on the

advice of the diabetes team

If blood glucose still rises > 10mmol/l when not in labour despite additional bolus doses of short acting insulin, a sliding scale insulin should be commenced according to labour ward protocol. This can be in addition to s/c insulin if the women is still eating. If labour immient have lower threshold for proceeding to sliding scale ie BM> 8mmol/l. Seek advice about

discontinuing sliding scale (Diabetic team/Miss Sudhakar/Miss Pandher).

Urinalysis for ketonuria when hyperglycaemic. If more than 1+ ketones treat as DKA and seek advice from diabetes team or Medical SpR out of

hours. Check all urine samples thereafter until no ketones.

Daily CTG with increased frequency if hyperglycaemic (risk of acidosis during hyperglycaemia). Continuous CTG

if on sliding scale.

NB: Normal insulin is continued and women eats and drinks normally. Intravenous glucose is NOT required in this situation unless the woman is Fasting/ Unable to eat & drink1. Insulin Dosage Calculation for VRIII* Regimen A B C D24 hour insulin requirements*

<40 units/day 41- 80 units/day 81-120 units/day >120 units/dayBlood Glucose (mmol/l)Hourly IV Insulin (ml/hr) (ml/hr) (ml/hr) (ml/hr)<6.0 0 0 0 06.1 – 7.0 0.5 1 2 37.1 – 8.0 1 2 3 58.1 – 9.0 1.5 3 4 79.1 -– 10 2 4 6 10> 10.1 3 6 6 13

*Calculate woman’s current 24 hour insulin requirements (short + long acting insulin) and then start on regimen according to this. e.g if taking 52 units daily start regimen B

2. When to alter VRIII regimen

a. If high CBG levels are not responding to the initial VRIII regimen (e.g. CBG >10mmol/l for two consecutive hourly measurements) the dosage regimen is moved up to the next level (e.g. if on regimen A move up to regimen B etc.)b. If CBG level is below 4mmol/l on one occasion the dosage regimen is moved down one level (e.g. if on regimen C, move down to regimen B).

Diabetes care on the labour ward

• Target BG 4-7mmol/L during labour• Most women with type 1 and type 2 diabetes will

commence VRII once in labour (individualized protocol if on a pump)

• Women with GDM will commence VRII only if BM>7• Check BM 1 hour after delivery and continue to adjust

insulin until eating and drinking• Insulin requirements will drop immediately after

delivery. Post partum insulin doses recorded in hand held notes.

The glucose infusion must not be discontinued, regardless of the CBG result.Blood Glucose (mmol/l) Insulin infusion rate (ml/hr)< 4* 04 - 6.9 17 - 8.9 29 - 10.9 311 – 17 4> 17** 6Long acting insulin analogues (i.e. Lantus or Levemir) should be given as normal i.e. in addition to the VRIII – once in labour these should be given using the Postpartum doses written on the front of the ICP.

1Altering the insulin infusion rate prescription* If CBG <4, the insulin infusion should be stopped and hypoglycaemia treated according to the protocol.** If CBG >17, check IV lines and review the insulin infusion prescription as below.· If the infusion rate is constantly 4 or 6 ml/hr without achieving a satisfactory CBG level (insulin resistant), the insulin infusion prescription should be altered, increasing the infusion rate for each glucose band.· If the infusion rate is running at 0 or 1 ml/hr and the CBG level is constantly low (insulin sensitive), the insulin infusion prescription should be altered, decreasing the infusion rate for each glucose band.

Summary• Increased risk of adverse outcome particularly in pre existing

diabetes. Microvascular complications, high Hba1c, hypertension, IUGR or macrosomia/polyhydramnios are all adverse risk factors

• Be aware that glycaemic targets are MUCH tighter in pregnancy. • Watch out for

- Hypo’s- Ketosis complicating acute illness/hyperglycaemia- euglycaemic DKA

• Insulin requirements drop immediately after delivery• Involve diabetes/obstetric team early.