Associated Conditions and DiabetesPREGNANCY Manuela Carvalheiro, MD, PhD Head of the Department of...

Associated Conditions and Diabetes

PREGNANCY PREGNANCY

Manuela Carvalheiro, MD, PhD

Head of the Department of Endocrinology Diabetes and Metabolism, Hospital da Universidade de Coimbra. Portugal

Professor Endocrinology, Coimbra Medical School, Portugal

Member of MGSD Board

Consultant Adviser of Portuguese Health Ministry for Diabetes

http://www.mgsd.net/index.asp

Diabetes and Pregnancy. Are we providing the best care? Findings of a national enquiry. Fevereiro 2007. http://www.cemach.org.uk

Diabetes and pregnancy. Are we providing the best care? Findings of a national enquiry. Fevereiro 2007. http://www.cemach.org.uk

Diabetes and pregnancy. Are we providing the best care? Findings of a national enquiry. Fevereiro 2007.http://www.cemach.org.uk



Diabetes and pregnancy. Are we providing the best care? Findings of a national enquiry. Fevereiro 2007 http://www.cemach.org.uk

Management of Pregestational Diabetes

Mathiesen E. Center for Pregnant Women with Diabetes, Copenhagen. SPSG Audit Meeting, 2006

Perinatal Mortality Women with type 1 or Type 2 Diabetes

Mary C M Macintosh et al. Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study BMJ 2006;333:177 (22 July),

Congenital anomalies of women with type 1 or type 2 Diabetes

Mary C M Macintosh et al. Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study BMJ 2006;333:177 (22 July),

Annunziata Lapolla, Italy. DPSG Audit meeting, 2006

Annunziata Lapolla, Italy. DPSG Audit meeting, 2006

Diabetes and Pregnancy

MothersInfants

Diabetes and Pregnancy • The Health Authorities must ensure that women with DM are provided with

specialist Services to preconception and pregnancy care with access to all

members of a multidisciplinary team adequately prepared

– As a minimum, these services should include:

• Clear signposting to different aspect of care

• Diet and lifestyle advice

• Provision of appropriate contraception (pregnancy planning and post-

partum)

• Smoking cessation support

• Assessment and management of diabetes complications

• Setting of glycemic targets and regular discussion of self-monitoring to

enable the women to achieve a near normal control before conception and

during pregnancy

• Discussion of diabetes pregnancy risks and expected management strategies

• Clear documentation of care and counselling, idealing using a standard

template

Pregestational diabetes Preconception care

Medical and obstetric historyDuration and type of diabetesAcute and chronic complicationsDiabetes management: insulin regimens, SMBG, hypoglycemia, nutrition (C.H counting), psychosocial status......

Concomitant medical conditionsMenstrual/pregnancy history, contraceptive useSupport system, including family and work environment

Physical examinationBlood pressure evaluation Retinal examinationCardiovascular examinationNeurologic assessmentPelvic examination

Clinical Practice Recommendations 2000. Diabetes Care S65


Laboratory evaluationA1cBaseline assessment to renal function: microalbuminuria, creatinine....Thyroid evaluationOther tests as indicated by physical exam and history

Management plan (discussion with the patient and her partner concerning management goals during pregnancy)

Intensive insulinotheraphy: MII (short acting insulin analogs + NPH); pump infuser

Adequate supplementation therapy: folic acid 400µg/daily, vitamins, iron....

Education therapy: instruction of insulin adjustment...SMBG, performed with memory meters: 6-8 times daily

Urine (blood) ketone testing: if blood glucose >200 mg/dl (>11 mmol/L)

Treatment/stabilisation of chronic complications: hypertension, retinopathy, renal disease....



Goals to be achieved with therapy SMBG

Preprandial 70 –100 mg/dl (3.9 5.6 mmol/L)

Postprandial1h<140 mg/dl (<7.8 mmol/L)2h <120 mg/dl (6.7 mmol/L)

Plasma glucosePreprandial

80 – 110 mg/dl (4.4 6.1 mmol/L)Postprandial

1h<155 mg/dl (<8.6 mmol/L)2h <135 mg/dl (7.5 mmol/L)

HbA1cWithin or near (<1%) the upper limit of normal for the laboratory


Pregestational diabetes After conception

• The metabolic alterations in early pregnancy include loss of glucose and gluconeogenic substrates (especially during the night)

• In midgestation insulin requirements begin to increase as the women changes to a lipid–based energy economy

• In late gestation insulin resistance due to the placental contrainsulin hormones result in greater insulin requirements

• In postpartum insulin injections may not be necessary for as long as 48–72 h due to release of insulin stores created prepartum

• Insulin needs must be recalculated using postpartum weight exercise and breast–feeding

Medical Management of pregnancy complicated by diabetes. 2ª edition. Ed: L Javanovic. ADA1995


Biweekly visits until week 32 (34) then weekly

Follow-up with an identical management protocol of the preconception period to reach the glucose goals

In each visit clinic evaluation of weight, blood pressure evaluation/discussion of the SMBG recording

Monthly, serial A1c, blood glucose at fasting, 1h and 2h after breakfast, urine samples for bacteriuria

In each trimester measurements of 24-hour urine collection for microalbumin and creatinine (creatinine clearance), fasting lipids and ophthalmologic evaluation

Continuous Glucose Monitoring (CGMS®MiniMed) is performed as adjuvant of traditional SMBG

The real time CGMS (Guardian RT® MiniMed; Paradigma RT®…) promise a significant reduction of SMGG number and also a better assessment to the awareness glycaemic excursions

Portuguese Consensus Report on Diabetes and Pregnancy. Ed. Carvalheiro M. SPEDM. 2ª Edition 1999.

DM1DM129 years29 years21 Week21 WeekHumalog-6+4+6+(4)Humalog-6+4+6+(4)NPH-14NPH-14HbA1c- 5%HbA1c- 5%DTI = 34 U/dayDTI = 34 U/day

Glucose Sensor ProfileModal Day

-50

0

50

100

150

200

250

300

350

400

12:00AM

4:00 AM 8:00 AM 12:00PM

4:00 PM 8:00 PM 12:00AM

Time

Glu

cose

Con

cent

ratio

n (m

g/dL

)18-Nov-02

19-Nov-02

20-Nov-02

21-Nov-02

Continuous glucose monitoring can diagnose high postprandial blood

glucose levels and nocturnal hypoglycemic events that are unrecognized

by intermittent blood glucose monitoring and may serve as a basis for

determining treatment regimens.


In each visit obstetric clinic evaluation

Ultrasound examination at 8 and 12 weeks (vaginal), then follow-up every 4 to 6 weeks (38 weeks included)

Doppler velocimetry initiated at 32 weeks

Nonstress test weekly initiated at 36 weeks (earlier if maternal vasculopathy) and daily after 38 weeks

Fetal biophysical profile initiated at 32 weeks, being daily after 38 weeks (if necessary)

Daily fetal movements counts initiated at 32 weeks

Fetal echocardiogram at 23 and 32 weeks

Portuguese Consensus Report on Diabetes and Pregnancy. Ed. Carvalheiro M. SPEDM. 2ª Edition 1999 .

Glucose goals to be achievedSMBG

Fasting 60–90 mg/dl (3.3-5.0 mmol/L

Premeal 60–105 mg/dl (3.3-5.8 mmol/L)

1h postprandial 100–120 mg/dl (5.5-6.7 mmol/L)

0200-0600 60–120 mg/dl (3.3-6.7 mmol/L)

Plasma glucose* Fasting 60–90 mg/dl (3.3-5.0 mmol/L)

Postprandial 1ª <140 mg/dl (7.8 mmol/L)

2ª <120 mg/dl (6.7 mmol/L)

Nocturnal 60-120mg/dl (3.3-6.7 mmol/L)

HbA1cWithin or near the nondiabetic level

Medical Management of pregnancy complicated by diabetes. 2ª edition. Ed: L Javanovic. ADA 1995 *Witznitzer and Reece. 1999



Delivery: – Timing

After the 38 week (38–40) in women with good metabolic control and no maternal/obstetric and fetal complications

– Mode

Vaginal, unless macrosomia, fetal distress and/or maternal proliferative retinopathy, other vascular disease....

– Intrapartum glycemic control

Hourly fingerstick blood glucose determinations

Blood glucose 70–90 mg/dl (3.9-5.0 mmol/L) or 100 mg/dl (5.5 mmol/L)

Short-acting insulin analogs and intravenous 5% dextrose solution (infusion)

Portuguese Consensus Report on Diabetes and Pregnancy. SPEDM. 2ª Edition 1999

Gestational Diabetes Definition

Gestational diabetes (GDM) is defined as carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy

The definition applies regardless of whether insulin is used for treatment or the condition persists after pregnancy

At 6–12 weeks postpartum, all women who had GDM should be evaluated and reclassified with a 75g OGGT (W.H.O. criteria)

Proceedings of the Fourth International Workshop-Conference on GDM. Diabetes Care, 21, 1998

Gestational Diabetes Epidemiology

Increasing Incidence of GDM: A Public Health Perspective. Assiamira Ferrara, MD, PhD. 5th International Workshop-Conference on Gestational Diabetes. November 11-13, 2005 . USA

Gestational Diabetes Epidemiology

+

Increasing Incidence of GDM: A Public Health Perspective. Assiamira Ferrara, MD, PhD. 5th International Workshop-Conference on Gestational Diabetes. November 11-13, 2005 . USA

Screening and Diagnosis of Gestational Diabetes

Universal screening*(without regarding time of the day or last meal)

At 24–28 weeks Plasma glucose measurement 1 h after 50–g GCTA value of 140 mg/dl (7.8 mmol/L)

identifies women at risk for GDM

DiagnosisA 100–g 3 hours OGTT, performed in the morning after an overnight fast and 3 days of unristricted diet (150 g C.H./day)

Two or more of the plasma glucose must be met or exceeded for the diagnosis (Carpenter and Counstan criteria):

Fasting 95 mg/dl (5.3 mmol/L)

1h 180 mg/dl (10.0 mmol/L)

2h 155 mg/dl (8.6 mmol/L)3h 140 mg/dl (7.8 mmol/L)

Portuguese Consensus Report on Diabetes and Pregnancy. SPEDM. 2ª Edition 1999Adapted from the Proceedings of the 4th International Workshop-Conference on GDM. Diabetes Care, 21, 1998

*The screening should be anticipated in case of high risk and repeated at 24-28 and 32 wk if negative



HAPO Highlights will be presented HAPO Highlights

Management of Gestational Diabetes

Metabolic managementNutritional therapy, individually tailored based on the pre-

pregnancy BMIExercise therapyInsulin therapy, if the metabolic goals fail to be achievedEducational therapyMetabolic surveillance: SMBG – 4 times daily (6–8) in

fasting and 1h postprandial A1c performed each 4–6

weeks ?

ObstetricDaily fetal mouvements counts after 36 weeksNonstress test weekly, after the 36 weeks Ultrasound each for 4–6 weeks after the diagnosis of GDM

DeliveryVaginal at 38–40 wk, unless macrosomia and/or obstetric or

other fetal distress


Gestational Diabetes

The Goals of Metabolic Management in GDM. Moshe Hod. 5th International Workshop-Conference on Gestational Diabetes. November 11-13, 2005 . USA



Goals to be achievedPrevention of adverse perinatal outcome

SMBGFasting 95 mg/dl (5.3

mmol/l)1h (90m?) 120mg/dl (6.7

mmol/l)

Continuous Glucose Monitoring (CGMS®MiniMed, GlucoDay® …) should be performed as adjuvant of traditional SMBG, if possible

CGNS Real Time (GardianRT®MiniMed…)

A1c every 6 wks to assess overall glycaemic control


If the Goals are not achieved

Recommendations for pharmacologic therapy initiation (INSULIN*)

When two or more SMBG measurements within 1 or 2 weeks exceed:

Fasting glucose > 90 mg/dl (> 5.0 mmol/L) and/or

1h postprandial glucose >120 mg/dl (> 6.7 mmol/L)

* Insulin is still the drug recommended as pharmacological treatment (short–acting analogs; NPH, Mix Insulin)

Portuguese Consensus Report on Diabetes and Pregnancy. SPEDM. 2ª Edition 1999Adapted from the Proceedings of the 4th International Workshop-Cconference on GDM. Diabetes Care, 21, 1998


• Oral Drugs:– Metformin (Transplacental passage in-vivo & in-vitro; does not affect

placental glucose uptake; not protein bound)

• Women with PCOS; GDM, DMT2 (several studies)• Metformin appears to be safe during pregnancy and

lactation. Further studies are needed to evaluate long term effects in the infants

– Glyburide /Glibenclamide (Extensively protein bound 98-99%;

Single cotyledon model placental transport insignificant compared with

older SUs; not detected in cord blood when detectable in maternal blood;

not detected in breast milk)

• Women with GDM, DMT2 (several studies)

• Glyburide appears to be safe in GDM; insufficient controlled studies in type 2 DM. Further studies are needed to evaluate long term effects in the infants

Anne Dornhorst. Pharmacological choices in diabetic pregnancy: Oral drugs. DPSG Audit meeting 2006


• Long term effect to the mother and infant:

– Mother• Higher risk for DM or Intermediate

Hyperglyceamia;

• Metabolic Syndrome;

• CVD

– Infant• Obesity;

• Higher risk for DM or Intermediate Hyperglyceamia;

• Metabolic Syndrome

Diabetes and pregnancyA matter of Public Health

Increasing Incidence of GDM: A Public Health Perspective. Assiamira Ferrara, MD, PhD. 5th International Workshop-Conference on Gestational Diabetes. November 11-13, 2005. USA

Istanbul, 26–29th April, 2007

10th MGSD Congress

THANK [email protected]

mailto:[email protected]

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