William 2001

Diabetes William 2001

Classification • Gestational diabetes • Overt diabetes • Contraception

In 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+diabeticcontrol  ↓ perinatal mortality to 15% Now  perinatal mortality = near normal introduction

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 infectioninflammatory 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% classification

Type II Familial No HLA association Concordance rate in monozygotic twins 100% 40% of sibling+ 1/3 offspring abnormal GTT Pathophysiology: • Abnormal insulin secretion • Insulin resistance in the target cell Obesity  peripheral insulin resistance  exhaustion of β-cells

type Itype II Age of onset < 40 >40 Habitus normal to thin obese Genetic locus chromosome 6 unknown P. Insulin ↓ to absent normal to ↑ P.Glucagon ↑, suppressible ↑, resistant Insulin ttt responsive responsive/ resistant Sulfonylurea unresponsive responsive Acute ketoacidosishyperosmolar complication coma

OnsetFBSPP 2hourstreatment A1 Gestational <10 <120 diet A2 Gestational >105 >120 insulin age of onsetdurationcomplication 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 “ Classification during pregnancy

Diabetes is the most common medical complication of pregnancy. % = 2.6 of all live birth, 90% GD, 10%OD Diagnosis: • RBS > 200 mg/dL + symptoms: = polyuria = polydipsia = unexplained weight loss • FBS ≥ 126 mg/dL , because ≥ 126  dramatic ↑ retinopathy Diagnosis of overt diabetes

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

Definition: Carbohydrate intolerance with onset or 1st recognition during pregnancy. Some of GD are overt diabetes 1st recognized during pregnancy. Study: Fasting hyperglycemia < 24 weeks pregnancy outcome as class B = OD Early hyperglycemia = high risk group Detection of gestational diabetes

2 step test: 50 gm glucose  1 hour if ↑blood glucose  diagnostic 100 gm glucose • 1 step test: diagnostic 100 gm glucose 1 hour  sample Devices avoided in screening: • Reflectance photometer • Glucometer screening

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% reproducible Normal results are 90% reproducible

Low risk If 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 Selective screening

Average risk If 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 risk If 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

ACOG 1994 criteria for diagnosis of GD using 100gm glucose taken orally. GD is diagnosed when any 2 values are met or exceeded. National DiabetesCarpenterData Group&Coustan (1979) (1982) Fasting 105 95 1 hr 190 180 2 hr 165 155 3 hr 145 140 Diagnostic criteria

Carpenter criteria: • ↑ 54% the number of pregnant women with diagnosis of GD • minimally affect % macrosomia • ↑ cost 75 gm test: used in Europe 100 gm test + 3 hour pp: used in USA 70% of physician use: National Diabetes Data Group criteria

Maternal and fetal effects • Management • Obstetric management • Postpartum consequences Gestational diabetes

GD induced by pregnancy may be : • Exaggerated physiological changes • Type II 1st recognized during pregnancy Study: % of undiagnosed DM between 20-44 years ♀ = % of GD Study: 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 ♀ = normal The only problem is: ↑ fetal size  birth injures 50% of GD  overt D within 20 years + ↑ % of DM + ↑ % of obesity in their offspring

Fetal anomalies are not ↑ in A1 & A2 Fetal death  normal in A1 as overt D in A2 Macrosomia: • 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 Maternal and fetal effects

% 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 adiposity Insulin-GF I, insulin-GF II: Pro-insulin-like peptides Produced by nearly every cell Potent stimulators for cell division&differentiation Cord blood level of: Insulin, IGF-I, IGF-II correlate with birth weight

Maternal obesity is more important risk factor than glucose intolerance in GD Study: 8% of women > 250 pounds have GD < 1% of women < 200 pounds Study: ↑ risk of GD in women with truncal obesity

ACOG: If FBS ≥ 105 mg/dL 2h PP ≥ 120 mg/dL insulin American Diabetes Association: If diet cannot keep capillary FBS ≤ 95 mg/dL 2 h pp ≤ 120 mg/dL insulin Diet Aim: • supply necessary nutrients • control glucose level • prevent starvation ketosis management

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

Indicated if diet cannot persistently keep FBS ≤ 105 mg/dL Hospitalization to: • Titrate insulin dosage • Educate the patient Dose 20–30 IU/day once before breakfast • 2/3 intermediate acting • 1/3 short acting insulin

Study: Post-prandialsurveillance is superior to pre-prandial surveillance  • ↓ CS • ↓ neonatal hypoglycemia • ↓ macrosomia Study: Both are equally important Study: Treatment by insulin+diet↓birth weight

Study: Insulin + diet  No ↓ birth weight Study: Strict glucose control # routine antenatalcare  little effect on: • Birth weight • Operative delivery • Neonatal complications

Study: Glucometer 7 times/day  • ↓ Macrosomia • ↓ CS • ↓ shoulder dystocia Oral hypoglycemics: Not recommended by ADA, Althoughno ↑ neonatal complications were detected in one study

A1 Spontaneous normal delivery No early induction No antepartum fetal testing Study: Elective induction in A1 ↓ shoulder dystocia to 0.7% # 2.2% in spontaneous delivery A2  as overt diabetes Obstetric management

As ½ GD  overt diabetes within 20 years, all GD most be tested 6-12 weeks pp If normal GTT  tested/3 years Patient and physician compliance = 30% A2 or insulin treatment < 24 weeks = DM pp Long - term risks in GD: • Type II DM • CVD due to ↑ lipids • HTN • Abdominal obesity Post-partum consequences

Risk is associated with: • Obesity • HTN • ↑ triglycerides Obese womenchange 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

Fetal effects • Neonatal effects • Maternal effects • Management Overt diabetes

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%

Abortion PTL Malformation Unexplained fetal death Hydramnios Fetal effects

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 % = ½ perinatal 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 preconceptionalglycemic 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↓ anomalies Mechanisms: • ↑glucose ↑free oxidative radicals=toxic • ↑glucose ↓specific gene activity  ↓arachidonicacid  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 ODplacental insufficiency Ketoacidosis can also cause fetal death V – Hydramnios ↑ glucose  ↑ AF glucose  hydramnios

Respiratory distress Hypoglycemia Hypocalcaemia Hyperbilirubinemia Cardiac hypertrophy Cognitive development Inheritance Altered growth neonatal effects

William 2001

William 2001

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