WILLIAM 2001

Diabetes

Classification Gestational diabetes Overt diabetes Contraception

INTRODUCTIONIn 1900 ↑ infertility

↑maternal mortality ↑perinatal mortality = 40%

In 1922 insulin discovery ↓infertility

↓maternal mortality, but same perinatal mortality

In 1949 White classification ↑severity = ↑ perinatal mortality

early termination by CS+diabetic control ↓ perinatal mortality to 15%Now perinatal mortality = near normal

CLASSIFICATION Classification during Pregnancy Diagnosis of Overt Diabetes during

pregnancy

Detection of Gestational Diabetes

- Screening - Diagnostic criteria

CLASSIFICATION

Type I Immune mediated Develop in genetically susceptible persons Triggered by viral infectioninflammatory insulitis autoimmune antibodies against β–cells cell destruction Associated with HLA D on chromosome 6 Low vertical transmission rate Concordance rate in monozygotic twins = < 50%

Type IIFamilialNo HLA association Concordance rate in monozygotic twins 100%

40% of sibling+ 1/3 offspring abnormal GTTPathophysiology:

Abnormal insulin secretion Insulin resistance in the target cell

Obesity peripheral insulin resistance exhaustion of β-cells

type I type IIAge of onset < 40 >40Habitus normal to thin obeseGenetic locus chromosome 6 unknown

P. Insulin ↓ to absent normal to ↑P.Glucagon ↑, suppressible ↑, resistantInsulin ttt responsive responsive/

resistantSulfonylurea unresponsive responsiveAcute ketoacidosis hyperosmolar

complication coma

CLASSIFICATION DURING PREGNANCY

Onset FBS PP 2hours treatmentA1 Gestational <10 <120

diet A2 Gestational >105 >120 insulin

age of onset duration complication B >20 <10 - insulin

C 10-19 10-19 - “ D <10 >20 benign retinopathy

“ F any nephropathy

“ R any proliferative

retinopathy“ H any heart disease

“

DIAGNOSIS OF OVERT DIABETES

Diabetes is the most common medical complication of pregnancy .

= %2.6 of all live birth, 90% GD, 10%ODDiagnosis:

RBS > 200 mg/dL + symptoms: = polyuria = polydipsia = unexplained weight loss FBS ≥ 126 mg/dL , because ≥ 126 dramatic ↑ retinopathy

Risk of OD ↑ in the presence of: Persistent glucosurea Strong family history Large infant Unexplained fetal deathA +ve dip-stick test= Augmented glomerular filtration, or Glucosurea evaluate

DETECTION OF GESTATIONAL DIABETES

Definition: Carbohydrate intolerance with onset or

1st recognition during pregnancy. Some of GD are overt diabetes 1st recognized during pregnancy .Study:

Fasting hyperglycemia < 24 weekspregnancy outcome as class B = ODEarly hyperglycemia = high risk group

SCREENING 2 step test: 50 gm glucose 1 hour if ↑blood glucose diagnostic 100 gm glucose 1 step test: diagnostic 100 gm glucose 1 hour

sampleDevices avoided in screening:

Reflectance photometer Glucometer

In 50 gm 1 hour blood sample: 140 mg/dL identify 80% of GD +ve in 14 – 18 % of women 130 mg/dL identify 90% of GD +ve in 20 – 25 % of women

50 gm test:Abnormal results are 83% reproducibleNormal results are 90% reproducible

SELECTIVE SCREENING

Low riskIf all are +ve no routine screening:

No DM in 1st degree relative No ethnic risk < 25 years Normal weight before pregnancy No poor obstetric outcome No history of abnormal GTT

Average riskIf 1 is +ve screen at 24-28 weeks

=Average:African, South and East Asian, Native Americans and Hispanics

=High: Marked obesity Strong family history Previous GD Glucosuria

High riskIf 1 is +ve screen as soon as possible:

=If GD is not diagnosed blood glucose testing should be repeated at:

24 - 28 weeks= At any time when the patient

develops: Symptoms Signs

DIAGNOSTIC CRITERIA

ACOG 1994 criteria for diagnosis of GD using 100gm glucose taken orally. GD is diagnosed when any 2 values are met or exceeded.

National Diabetes Carpenter Data Group &Coustan

( 1979( )1982 )Fasting 105 95

1 hr 190 1802 hr 165 1553 hr 145 140

Carpenter criteria: ↑ 54% the number of pregnant

women with diagnosis of GD minimally affect % macrosomia ↑ cost

75 gm test: used in Europe100 gm test + 3 hour pp: used in USA

70% of physician use: National Diabetes Data Group criteria

GESTATIONAL DIABETES

Maternal and fetal effects Management Obstetric management Postpartum consequences

GD induced by pregnancy may be : Exaggerated physiological changes Type II 1st recognized during pregnancy

Study: % of undiagnosed DM between 20-44

years ♀ = % of GDStudy :

Abnormalities of glucose metabolism in GD = abnormalities in overt D

Diagnosis of GD = need for ↑ surveillance need for pp testing

%of fetal death in treated ♀ = normalThe only problem is :

↑fetal size birth injures 50% of GD overt D within 20 years

% + ↑of DM % + ↑of obesity

in their offspring

MATERNAL AND FETAL EFFECTSFetal anomalies are not ↑ in A1 & A2Fetal death normal in A1

as overt D in A2Macrosomia:

Avoid difficult labor Characterize the fetus of diabetic mothers Affect all organs of the fetus except the brain Differ from other causes of macrosomia:

- ↑shoulder and trunk ↑ shoulder dystocia - ↑subscapular and triceps skin fold diameter

↑ % of CS due to CPD

%of shoulder dystocia in A1 = 3%Pathogenesis:

Maternal hyperglycemia maternal hyperinsu-linemia fetal hyperinsulinemia neonatal hypoglycemia ≤ 35 mg/dL (in preterm fetuses less value due to ↓ glycogen stores)

%of neonates requiring IV glucose in GD = 4%

Insulin:Produced by β-cells in the pancreas >20 weeks Stimulate somatic growth and adiposityInsulin-GF I, insulin-GF II :Pro-insulin-like peptides Produced by nearly every cell Potent stimulators for cell division&differentiationCord blood level of :

Insulin, IGF-I, IGF-II correlate with birth weight

Maternal obesity is more important riskfactor than glucose intolerance in GDStudy:

8% of women > 250 pounds have GD

<1% of women < 200 poundsStudy:

↑risk of GD in women with truncal obesity

MANAGEMENTACOG:

If FBS ≥ 105 mg/dL2h PP ≥ 120 mg/dL insulinAmerican Diabetes Association:

If diet cannot keep capillary FBS ≤ 95 mg/dL

2 h pp ≤ 120 mg/dL insulinDietAim :

supply necessary nutrients control glucose level prevent starvation ketosis

Caloric restriction in overweight women :

1200 - 1800 Kcal/day ↓hyperglycemia ↓ triglycerides No ↑ in ketonuria Improve glucose control ↓ need for insulin ↓ macrosomia ↓ maternal weight gain

Safety unknown, not recommended by ACOG Exercise

Upper cardiovascular exercises Improve glycemic control + diet Effect appears after 4 weeks

INSULIN

Indicated if diet cannot persistently keep

FBS ≤ 105 mg/dLHospitalization to:

Titrate insulin dosage Educate the patient

Dose 20–30 IU/day once before breakfast

2/3 intermediate acting 1/3 short acting

Study: Post-prandial surveillance is superior

to pre-prandial surveillance ↓ CS ↓ neonatal hypoglycemia ↓ macrosomia

Study: Both are equally importantStudy :

Treatment by insulin+diet↓birth weight

Study: Insulin + diet No ↓ birth weight

Study: Strict glucose control # routine

antenatal care little effect on: Birth weight Operative delivery Neonatal complications

Study:Glucometer 7 times/day

↓ Macrosomia ↓ CS ↓ shoulder dystocia

Oral hypoglycemics: Not recommended by ADA ,

Although no ↑ neonatal complications were detected in one study

OBSTETRIC MANAGEMENT

A1 Spontaneous normal delivery No early induction

No antepartum fetal testingStudy:

Elective induction in A1 ↓ shoulder dystocia to 0.7% # 2.2% in spontaneousdeliveryA2 as overt diabetes

POST-PARTUM CONSEQUENCES

As ½ GD overt diabetes within 20 years, all GD most be tested 6-12 weeks ppIf normal GTT tested/3 yearsPatient and physician compliance = 30%A2 or insulin treatment < 24 weeks = DM ppLong - term risks in GD:

Type II DM CVD due to ↑ lipids HTN Abdominal obesity

Risk is associated with: Obesity HTN ↑ triglycerides

Obese womenchange life style/control weight

Recurrence of GD = 60% Even if next pregnancy with normal GTT

no improvement of pregnancy outcome as : birth weight macrosomia neonatal complications

OVERT DIABETES Fetal effects Neonatal effects Maternal effects Management

Successful outcomes are related to: Diabetic control Intensity of underlying CVD/RD

Complications: Preeclampsia 21% PTL 25% Macrosomia 20% Growth restriction 1% Unexplained fetal death 2% Perinatal mortality 3%

FETAL EFFECTS

I. Abortion II. PTLIII. MalformationIV. Unexplained fetal deathV. Hydramnios

Perinatal mortality ↓ due to: Maternal glucose control Improved fetal surveillance ICU

%now = 2 – 4% Modern intervention did not ↓:

Chromosomal abnormalities Unexplained fetal death

I - Abortion: Type I = 24%

Associated with poor glycemic control in the 1st trimester

Risk ↑ in: Hg A1 > 12% Persistent preprandial glucose

> 120 mg/dL

II - PTL Spontaneous PTL = 9% # 4.5% Induced PTL = 7% # 2.0%

III – Malformation Type I = 5 – 10 %

= ½perinatal mortality in DM

Chromosomal anomalies are not ↑

Severity of malformation ↑ by: Poor early control Poor preconceptional control

Risk of malformation ↑ in: ↑ Hg A1 Vasculopathy Duration > 10 years

Studies:• ↓ Hg A1 is associated with ↓ malformation• Normal Hg A1 does not guarantee absence of malformation• ↑ Hg A1 is not a risk factor for malformation• ↓ preconceptional Hg A1 is associated with 5% malformation # 9%• Strict preconceptional glycemic control is

associated with 1.2% malformation # 11%

↑initial glucose level: ↑ single organ anomalies

↑↑initial glucose level: ↑ multiple organ anomalies

Most common single organ anomalies:

Heart 38% Ms/skeletal 15% CNS 10%

Animal studies: Vit E Antioxidants Lipoic acid

When given to pregnant rats↓ anomaliesMechanisms:• ↑glucose ↑free oxidative

radicals=toxic• ↑glucose ↓specific gene activity

↓arachidonic acid NTD

IV – Unexplained fetal death = 1% usually > 35 weeks & large

Case : Cord blood show ↓ pH

↑PHO2 ↑lactate

↑erythropoietin = ↑glucose chronic aberrations

in O2 and metabolite transport

Case:• Macrosomia• Hydramnios• Acidemic fetus• Hydropic placenta ( edema of chorionic villi ) ↓ transport of O2

Severe preeclampsia and vasculopathy

in advanced ODplacental insufficiency

Ketoacidosis can also cause fetal death

V – Hydramnios ↑glucose ↑ AF glucose

hydramnios

NEONATAL EFFECTS

I. Respiratory distressII. HypoglycemiaIII. HypocalcaemiaIV. HyperbilirubinemiaV. Cardiac hypertrophyVI. Cognitive developmentVII. InheritanceVIII.Altered growth

In the past early termination to avoid: Unexplained fetal death Macrosomia

Now PTL ≤ 36 weeks in 25% for: Preeclampsia Advanced diabetes

Modern neonatal ICU ↓ death due to prematurity

I – Respiratory distressIn the pastdelayed lung maturity in DMNow GA is the most important factorII – HypoglycemiaDue to hyperpleasia of β- islet of cellsIII – Hypocalcemia

< =7 mg/dL Unknown cause

Associated with: DM PTL Asphyxia

Study :1/3 cases of routine antenatal care

showed hypocalcemia # 18% in strict diabetic control

IV – HyperbilirubinemiaHTV is 65 – 70 vol % in 40% of:

Hemolysis Polycythemia PTL

Polycythemia may renal vein thrombosis

V – Cardiac hypertrophyOccur due to :

Macrosomia Hyperinsulinemia

May HFDisappear 6 months postpartumVI – Cognitive developmentDiabetes has minimal effect on IQ

VII – Inheritance Mother 1 – 3% Father 6% Both 20%

Most important risk factors intype I children:

Type I diabetic mother Older mothers

VIII – Altered growthAll diabetic fetuses are growth promotedEarly diabetic control affect macrosomiaIf mean maternal blood glucose is

>130 mg/dL ↑macrosomia AC by U/S is ↑ at 34 weeksStudy:Macrosomia can be seen < 24 weeks

MATERNAL EFFECTS

I. Diabetic nephropathyII. Diabetic retinopathyIII. Diabetic neuropathyIV. PreeclampsiaV. KetosisVI. infection

With the exception of retinopathy ,long - term course of diabetes is not affected by pregnancyMaternal mortality X 10 due to:

Preeclampsia HTN Ketosis Pyelonephritis

Class H maternal mortality = 50%

I – DIABETIC NEPHROPATHY

Leading cause of end-stage RD Type I = 30% RFType II = 4 – 20% RF

> %↓1980 due to improved controlSubclinical DN ↑ abruptly when Hb A1 = > 10%

Natural history of untreated cases:Onset of DM 5 years microalbuminuria = 30 – 300 mg/day 5 – 10 years albuminuria>300mg/day 5 – 10 years renal failureClass F

=5% of all diabetes ↑preeclampsia 50%

↑indicated PTL

Study: <20 weeks albuminuria > 500mg/day

↑ preeclampsia 38% microalbuminuria < 500mg/day

↑ preeclampsiaStudy:No↑of preeclampsia in microalbuminuria

Study:Chronic HTN + DN ↑ preeclampsia 60%Predictive of preeclampsia < 20 weeks:• Creatinine ≥ 1.5 mg/dl• Albuminuria ≥ 3 gm/day

Study:Pregnancy did not exacerbate DNStudy:

1 : 11 patients of class F RF 6 years pp

II – DIABETIC RETINOPATHY

Most important cause of visual impairment < 60 yearsAfter 20 years durationtype I 100% DR

type II 60% DRNatural history of untreated cases:

Microaneurysmsblot Hghard exudate =benign/nonproliferative/background R

=class D whatever the duration is

In more severe cases:Abnormal vessels occluded ischemia

( can obscure vision if Hg occur ) infarction cotton wool exudate

=preprolifetative R =class R whatever the duration is

Laser photocoagulation ↓ ½ of blindness induced by pregnancyStudy :

1/3 type I have D-R retinopathy develop by 10 weeksEffects of pregnancy on retinopathy:

Worsen PR # no effectStudy :

Progression of DR is associated with ↓fetal weight

Good glycemic control + laser photo-coagulation ↓ bad effects of pregnancyStudy:Sudden vigorous control of glucose acuteworsening of retinopathy, but slows progressionStudy:Retinopathy without nephropathy no

adverse fetal effectStudy:

¼DR at early pregnancy progressive eye disease during pregnancy despite good control

III - DIABETIC NEUROPATHY

UncommonDiabetic gastropathy:nausea VomitingNutritional problemDifficult controlTreatment:H2 receptor antagonist andMetoclopramide may be helpful

IV - PREECLAMPSIA

Major complication induced PTLPerinatal mortality X 20Not related to glucose controlRisk factors:

Preexisting albuminuria Vascular complications Chronic hypertension

V - KETOSIS =1%

Fetal death = 20%Causes:

Hyperemesis gravidarum β sympathomimetics in tocolysis Corticosteroids Infection Noncompliance

Recurrence :½ recurrent ketosis successful

pregnancy

VI - INFECTIONStudy:

80% of diabetic mothers develop 1 episode of infection #25% in nondiabeticsCauses:

Candida vulvovaginitis RTI UTI Pyelonephritis Puerperal sepsis

Screening for asymptomatic bacteriuoria % ↓of infection

MANAGEMENT

I. PreconceptionII. 1st trimesterIII. 2nd trimesterIV. 3rd trimesterV. Delivery

I. PRECONCEPTION

To prevent: early fetal loss congenital anomalies

Unplanned pregnancies = 60%Optimal preconceptional GTT:

Preprandial 70 – 100 mg/dL Postprandial 1h < 140 mg/dL 2h < 120 mg/dL

Glycosilated Hg A1, A1c: Indicate glucose control during the last 1 - 2 months Should be normal or X 3 SD of normal

mean If Hg A1 or A1c > 10% ↑ congenital

anomaliesFolate:

400 μgm/day ↓ NTD

II. FIRST TRIMESTER

Early hospitalization for: Titration of glucose level Education of the patient Assessment of vascular complications Establishment of GA

Treatment: Diet Insulin

Oral hypoglycemics: ↑ congenital anomalies Fetal hyperinsulinemia

Devices used: SC insulin pump Nocturnal hypoglycemia Select patient with care Self monitoring by glucometer New painless automatic device extract glucose by iontophoresis minimal skin irritation

Diet:30 – 35 kcal/kg of ideal body weight

3 meals + 3 snakes Carbohydrates 55% Proteins 20% Fat 25%(<10% saturated

fat)Obese patients require less calories, avoid:

Ketonuria Weight loss

It is not always possible to normalize

glucose level individualize treatment& avoid hypo/hyperglycemia

1st trimester usually unstable 14 – 24 weeks are stable 24 weeks ↑ insulin requirement

due to ↑pregnancy hormones = insulin antagonists

Study:↑ insulin requirement α maternal weight/diabetic durationStudy :

70% of diabetics develop 1 episode of hypotension, peak between 10-15 weeks:

¼ unconsciousness 15% convulsions

Patients with recurrent hypotensioncaution

2ND TRIMESTER

α – fetoprotein: at 16 – 20 weeks

Target U/S at 18 – 20 weeks

can detect 70% of congenital anomalies

3RD TRIMESTERVisits / week for:

HTN glucose control

U/S every 3 - 4 weeks for: AFI macrosomia

Hospitalize if: HTN Difficult control Type I > 34 weeks until delivery

Fetal surveillance : Starts at 26 – 32 weeks

Unexplained fetal death : Usually > 36 weeks

Study: ↓requirement of insulin = impending

deathStudy:

Occur in 5% of normal fetuses

DELIVERY

Ideally near term -If GA is certain

deliver when 38 weeks are completed Tests of lung maturity are not done

-If GA is uncertain L/S ratio if ≥ 2 deliver

-If HTN deliver even if L/S ratio < 2 -If PTL avoid β sympathomimetics

Use corticosteroids with caution

CS rate = 50 – 80%Class B – C C SInduction if:

Fetus not excessively large Cervix favorable

-Shift to regular insulin -Measure blood glucose frequently

-Hydrate by glucose 5% -1st 24 hours may not require insulin

-Next days glucose level fluctuate largely -Treat infection

CONTRACEPTION

All methods can be used except implants