Insulin in GDM Ver 2.0

Gestational Diabetes Mellitus

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Agenda

• Gestational Diabetes Mellitus • Epidemiology• Risk Factors • Clinical features• Diagnosis• Treatment • Postpartum follow-up• Potential Complications • Conclusion

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Gestational Diabetes Mellitus (GDM)

• Defined as any degree of glucose intolerance with onset or first recognition during pregnancy

• Women with GDM:– May have only a minimal insulin deficiency

• Control blood glucose adequately with a meal plan– May have a more severe insulin deficiency

• Require insulin along with nutritional therapy

American Diabetes Association. Diabetes care 2004;27 Suppl1:S88-S90Joslin diabetes center Available at: http://www.joslin.org/info/diabetes-glossary.htmlAccessed on 02/11/2011

http://www.joslin.org/info/diabetes-glossary.htmlAccessed%20on%2002/11/2011

http://www.joslin.org/info/diabetes-glossary.htmlAccessed%20on%2002/11/2011

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Gestational Diabetes Mellitus (contd…)

• GDM may revert to impaired glucose tolerance (IGT) or even normal glucose tolerance after delivery

• GDM usually lasts only through the pregnancy

• Women with diabetes may be at greater risk of developing T2DM later stages of life (30–60%)

Joslin diabetes center Available at: http://www.joslin.org/info/diabetes-glossary.htmlAccessed on 02/11/2011

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Gestational Diabetes Mellitus (contd…)

• Long-term considerations in GDM:– Obesity and other factors promote insulin resistance

• Enhance the risk of T2DM after GDM

– Markers of islet cell–directed autoimmunity are associated with an increase in T1DM risk

– Offspring of women with GDM are at increased risk:• Obesity• Glucose intolerance• Diabetes in late adolescence and young adulthood

American Diabetes Association. Diabetes care 2004;27 Suppl1:S88-S90

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Agenda

• Gestational Diabetes Mellitus • Epidemiology• Risk Factors • Clinical features• Diagnosis• Treatment • Potential Complications • Conclusion

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Epidemiology of GDM

• Affects nearly 7% of all pregnancies– More than 200,000 cases annually

• Nearly 50% of women with a history of GDM develop T2DM within 5 – 10 years after delivery

• GDM in India:– More common in women living in urban areas than in the

rural areas

American Diabetes Association. Diabetes care 2004;27 Suppl1:S88-S90IDF Available at : http://www.idf.org/types-diabetes Accessed on 23/11/2011Ferrara A. Diabetes Care. 2007;30 Suppl 2:S141-6.

http://www.idf.org/types-diabetes

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Agenda


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Risk Factors for GDM

• Maternal demographic and physical factors:– Ethnicity (non - European)– Increasing age– Family history of diabetes– Short stature– Low birth weight– Parity

McCance DR, et al. Practical manual of Diabetes in Pregnancy. 1st Edition. Willey-Blackwell.2010:35-65.

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Risk Factors for GDM (contd…)

• Maternal clinical factors:– Overweight/obesity– Diet high in red and processed meat– Pregnancy weight gain– Physical inactivity– Polycystic ovarian syndrome– α - thalassemia trait– High blood pressure– Multiple pregnancy


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Risk Factors for GDM (contd…)

• Past obstetric history– Macrosomia– Stillbirth– Past GDM


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Risk Category and Clinical Characteristics

• High risk– Marked obesity– Diabetes in first-degree relative– Current glycosuria– Previous history of GDM or– Glucose intolerance– Previous infant with macrosomia

• Average risk– Neither high or low risk

Perkins JM, et al. Clinical diabetes. 2007;25(2):57-62.

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Risk Category and Clinical Characteristics (contd…)

• Low risk– Age < 25 years– No previous poor obstetrical outcomes– Belongs to a low-risk ethnic group*– No diabetes in first-degree relatives– Normal prepregnancy weight and– Weight gain during pregnancy– No history of abnormal glucose tolerance


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Agenda


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Clinical Features of GDM

• Unusual thirst• Frequent urination• Fatigue• Nausea • Frequent infections of bladder, vagina and skin• Blurred vision• Sugar in urine

Available at : http://www.americanpregnancy.org/pregnancycomplications/gestationaldiabetes.html. Accessed on 09/12/2011

http://www.americanpregnancy.org/pregnancycomplications/gestationaldiabetes.html



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Agenda


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Diagnosis of GDM

• Risk assessment for GDM should be undertaken at the first prenatal visit

• High risk of GDM: – Marked obesity– Personal history of GDM– Glycosuria– Strong family history of diabetes

• Essential for Indian pregnant women:– Eleven-fold increased risk of developing glucose intolerance

during pregnancy as compared to Caucasian women• Essential to undergo glucose testing as soon as feasible

American Diabetes Association. Diabetes care 2004;27 Suppl1:S88-S90Wahi P, et al. J Assoc Physicians India. 2011;59:227-30.

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Diagnosis of GDM (contd…)

• Women with low-risk do not require testing:– Age<25 years– Normal weight before pregnancy– Member of an ethnic group with a low prevalence of GDM– No known diabetes in first-degree relatives– No history of abnormal glucose tolerance– No history of poor obstetric outcome


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• Use standard diagnostic criteria to screen for T2DM at the first prenatal visit in those with risk factors:– HbA1c ≥ 6.5% OR– Fasting plasma glucose is ≥ 126 mg/dL OR– 2-h plasma glucose during OGTT ≥ 200 mg/dL OR– Random plasma glucose ≥ 200 mg/dL in a patient with classic

symptoms of hyperglycemia or hyperglycemic crisis

American Diabetes Association. Diabetes Care 2012; 35 (suppl 1)

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• In pregnant women not previously known to have diabetes, screen for GDM at 24–28 weeks’ gestation, using a 75-g 2-h OGTT– GDM is diagnosed if any of the following plasma glucose

values are exceeded:• Fasting ≥ 92 mg/dL• 1 h ≥ 180 mg/dL• 2 h ≥ 153 mg/dL


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Glycaemic Goals in GDM

• SMBG:– Preprandial ≤ 95mg/dL and either:– 1-h postmeal ≤ 140mg/dL or– 2-h postmeal ≤ 120mg/dL

• HbA1c < 6%


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Agenda


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Treatment of GDM

• Medical nutrition therapy (MNT)– For all women with GDM– Individualized – Provision of adequate calories and nutrients to meet the

needs of pregnancy– Consistent with the maternal blood glucose goals


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Treatment of GDM (contd…)

• Insulin is the drug of choice when medical nutrition therapy alone does not provide adequate control

• Oral hypoglycaemic agents are generally not recommended during pregnancy

• SMBG guides the insulin doses and regimen timings

• Insulin analogues not been adequately tested in GDM


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Treatment of GDM (contd…)Calculation of Insulin Dose

• Weight in kilograms × k = total insulin requirement,– k = 0.7, 0.8, and 0.9 for first, second, and third trimesters,

respectively

• 50% of total insulin requirement = Daily basal insulin dosage– Administered before breakfast (8:00 A.M.), before supper

(4:00 P.M.), and at midnight

Angelina L. Diabetes Spectrum.2007; 20( 2):94-101

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• NPH insulin have been used extensively to treat GDM

• If the FPG > 90 mg/dl, then NPH at a dose of 0.2 units/kg/day should be initiated at bedtime

• Next, if both FPG and PPG levels are elevated, a rapid- acting analog should be added with meals


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• Administer insulin based on FPG, pre-meal, and 1-hour postprandial glucose readings– Treat high FPG with bedtime NPH– Treat pre-dinner hyperglycemia with pre-breakfast

NPH– Treat bedtime hyperglycemia with pre-dinner NPH– Treat abnormal postprandial glucose with rapid-acting

insulin (lispro or aspart) immediately before the offending meal

Jovanovic L,. Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, Va: American Diabetes Association; 2000:111-132

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• May need up to 6 injections/day (3 NPH, 3 lispro or aspart), same as protocol for preexisting diabetes

• Evaluate regimen for 1 week– Adjust as needed to maintain blood glucose levels

• <90 mg/dL before meals • <120 mg/dL 1 hour post-meal

Jovanovic L,. Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, Va: American Diabetes Association; 2000:111-132

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Treatment of GDM (contd…)Role of Insulin Analogues• Human insulin: – Least immunogenic commercial preparation

• Rapid-acting insulin analogues: lispro and aspart:– Develop antibodies at rates and titers are comparable to

human regular insulin1

– Short duration of action– Better control postprandial glycaemia– Less postprandial hypoglycaemia than regular insulin– More effective than regular human insulin in achieving goal

glucose levels and reducing the risk of fetal macrosomia– Not been found to cross the placenta2

1. Metzger BE, et al. Diabetes Care. 2007 ;30 Suppl 2:S251-60.2. Perkins JM, et al. Clinical diabetes. 2007;25(2):57-62.

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Treatment of GDM (contd…)Role of Insulin Analogues

• Lispro and aspart have been investigated in pregnancy and demonstrated:– Clinical effectiveness– Minimal transfer across the placenta– No evidence on teratogenesis– Improves postprandial glucose excursions compared with

human regular insulin – Lower risk of delayed postprandial hypoglycaemia

Metzger BE, et al. Diabetes Care. 2007 ;30 Suppl 2:S251-60.

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Treatment of GDM (contd…)Role of Insulin Analogues

• Glulisine use in pregnancy: No reports are available• Insulin preparations of low antigenicity:– Minimizes the trans placental transport of insulin

antibodies

Metzger BE, et al. Diabetes Care. 2007 ;30 Suppl 2:S251-60.

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Treatment of GDM (contd…)Role of Insulin Glargine

Studies Type of diabetes

n Treatment with glargine Outcome

Woolderink et al.

Type 1 7 5 Treated throughoutpregnancy; 2 beganglargine in second trimester

HbA1C 6.4% No congenital malformations

Dolci et al. Type 1 andAddison’s disease

1 Second trimester Compared to NPH in first trimester,better control with glargine

Di Cianni et al. Type 1 5 First trimester No congenital malformations

Devlin et al. Type 1 1 Second and third trimester Better glycemic control with glargine than NPH

Holstein et al. Type 1 1 First, second, and third trimester

Better glycemic control with glargine than NPH

Torlone et al Type 1 6 First, second, and third trimester

Normal outcome

Trujillo. Diabetes Spectrum. 2007;20(2):94-101.

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Treatment of GDM (contd…)Role of Insulin Analogues• Insulin glargine does not cross the human placenta to a

measurable extent

• Rapid-acting analogues have the advantage of dosing 5–10 minutes before meals, vs. 30–45 minutes before meals with regular insulin

1. Erika K.. Diabetes Care. 2010;33(1):29-33. 2. Perkins JM, et al. Clinical diabetes. 2007;25(2):57-62.

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Agenda

• Gestational Diabetes Mellitus • Epidemiology• Risk Factors • Clinical features• Diagnosis• Treatment• Postpartum follow-up• Potential Complications • Conclusion

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Follow-up

• Monitoring blood glucose at home is important:– Tailoring specific treatment– Making adjustments as needed– Several studies have shown that monitoring four times daily

leads to more favorable glycaemic control– Check premeal and 2-hour postmeal glucose levels – Keep a track on carbohydrate consumption– Monitoring for fasting ketonuria in the morning

• Helps in guiding the level of carbohydrate restriction


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Postpartum follow-up

• Maternal insulin requirements drop markedly in the postpartum period– Because patients with GDM have a high risk of developing

T2DM• Important to continue screening these patients • Poor insulin secretion during pregnancy is predictive of

diabetes after delivery


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Postpartum follow-up (contd…)

• Patients need to minimize insulin resistance:– Exercise– Maintenance of normal weight– Avoidance of drugs that induce insulin resistance


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Postpartum follow-up (contd…)

• ADA recommendations:– An annual fasting blood glucose test– A 6-week postpartum 75-g 2-hour OGTT– Contraception to ensure that patients will not conceive in the

face of marked hyperglycaemia• Lead to increased congenital malformations and dysorganogenesis


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Conservative Recommendations to Women

• Let health care practitioners know of any history of GDM

• Get tested 6–12 weeks postpartum, then every 1–2 years

• Reach prepregnancy weight 6–12 months postpartum

• If still overweight, lose at least 5–7% of weight slowly, over time, and keep it off

Ratner RE. Diabetes Care. 2007;30 Suppl 2:S242-5.

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Agenda


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Potential Complications of GDM

• Obstetric and Perinatal Considerations in GDM:– Fasting hyperglycaemia >105 mg/dL

• Increased risk of intrauterine fetal death (last 4–8 gestation weeks)•GDM of any severity increases the risk of fetal

macrosomia•Following may complicate the GDM:–Neonatal hypoglycemia–Jaundice–Polycythemia–Hypocalcaemia


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Potential Complications of GDM (contd…)

• GDM is Associated with:– Increased frequency of maternal hypertensive disorders – Need for cesarean delivery

• Findings suggest: – GDM risk increases substantially with increasing maternal BMI

1. American Diabetes Association. Diabetes care. 2004;27 Suppl1:S88-S902. Chu SY. Diabetes Care. 2007;30(8):2070-6.

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Potential Complications of GDM

• Potential complications in infants of mothers with diabetes:– Intrauterine demise

• Spontaneous abortion• Stillbirth

– Macrosomia– Visceromegaly

• Cardiomegaly• Hepatic enlargement

Jovanovic L, 3rd ed. Alexandria. American Diabetes Association; 2000:133-149

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• Birth injury– Shoulder dystocia– Erb’s palsy– Diaphragmatic paralysis– Facial paralysis– Cerebral ischemia– Hemorrhage in brain, eyes, liver and genitalia


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• Asphyxia• Respiratory distress syndrome• Congenital malformations– Cardiac defects– Musculoskeletal deformities

• Metabolic abnormalities– Hypoglycaemia– Hypokalemia– Hypocalcemia– Hyperbilirubinemia– Erythrocytosis


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Diabetes Prevention for offspring:National Diabetes Education Program

• Modest weight loss and physical activity can delay or prevent T2DM

• Offspring can lower risk by:– Eating healthy foods– Being active– Avoiding overweight

Ratner RE. Diabetes Care. 2007;30 Suppl 2:S242-5.

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Conclusion

• Women with GDM are at greater risk of developing T2DM in later stages of life (30–60%)

• Tight glycaemic control is essential to prevent maternal and neonatal complications

• Insulin is the drug of choice if MNT alone cannot achieve adequate glycaemic control

• Increasing evidence in favour of insulin glargine use in pregnancy

• Women with GDM need regular follow up postpartum

Documents

Insulin in GDM Ver 2.0