Testing RR or OR (95% CI) Initial Visit Obese (BMI 30) 2.90 - - PowerPoint PPT Presentation

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Testing RR or OR (95% CI) Initial Visit Obese (BMI 30) 2.90 - - PowerPoint PPT Presentation

Dec 24, 2023 205 likes •357 views

Disclosures Diagnosis and Management of Diabetes in Pregnancy I have nothing to disclose Kirsten Salmeen, MD Assistant Professor, Maternal-Fetal Medicine Department of Obstetrics, Gynecology &

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SLIDE 1
  • Diagnosis and Management of

Diabetes in Pregnancy

Kirsten Salmeen, MD Assistant Professor, Maternal-Fetal Medicine Department of Obstetrics, Gynecology & Reproductive Sciences

Disclosures I have nothing to disclose Gestational Diabetes Mellitus (GDM)

“Carbohydrate (glucose) intolerance with onset

  • r first recognition during pregnancy.”

Previously Unrecognized Type 2 Diabetes Gestational Diabetes

Overview

Physiology

Testing Pregnancy Outcomes Treatment Pregnancy Management Postpartum Care

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SLIDE 2
  • Glucose & Insulin

Glucose Insulin Cell

Bloodstream Insulin Receptor

Causes of Hyperglycemia:

Insufficient Insulin Insufficient Insulin Receptor Sensitivity Glucose >> Insulin

Carbs Glucose

Glucose & Insulin – Pregnancy

The fetus uses glucose as its primary substrate,

makes its own insulin

Human placental lactogen & progesterone:

Decreased gastric motility Reduced insulin receptor sensitivity

Maternal hyperglycemia fetal

hyperglycemia fetal hyperinsulinemia excess fetal growth

Glucose & Insulin – Pregnancy

Hernandez et al. Diabetes Care. 2011;34(7):1660-8.

Mean Glucose – Normal Pregnancy

Fasting: 71 +/- 8 (63 – 79) mg/dL 1 hr PP: 109 +/- 13 (96 – 122) mg/dL

Normal pregnancy: Mild fasting hypoglycemia Postprandial hyperglycemia Hyperinsulinemia

Pregnancy = “Pancreatic Stress Test”

Glucose & Insulin – Pregnancy

Cunningham et al. Williams Obstetrics, 23rd Edition: http://www.accessmedicine.com. Redrawn from: Phelps et al. Am J Obstet Gynecol. 1981;140(7):730-6.

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SLIDE 3
  • Overview

Physiology

Testing

Pregnancy Outcomes Treatment Pregnancy Management Postpartum Care

33 year-old G2P1 at 11 weeks, BMI = 27, Caucasian, no PMH. First pregnancy: 3 years ago, 50g 1hr glucose test at 26 weeks 138 mg/dL, 3800 g NSVD. Obese aunt with type 2 DM. What is your first test?

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43% 21% 2% 32% 2%

  • A. Hemoglobin A1c today
  • B. 50 g 1 hour glucose test today
  • C. 75 g 2 hour glucose test today
  • D. 50 g 1 hour glucose test at 24 – 28 weeks
  • E. 75 g 2 hour glucose test at 24 – 28 weeks

Testing Goal

Identify chronic hyperglycemia as soon as it exists

0 - 6.5 6.6 - 8.0 8.1 - 9.4 9.5 - 11.1 > 11.2

Percentage

www.cdc.gov/diabetes

2009 County-Level Estimates Diagnosed Diabetes, Adults ≥ 20 Years

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SLIDE 4
  • Testing – Who is High Risk?

RR or OR (95% CI) Obese (BMI ≥ 30) 2.90 (2.15 – 3.91) History of GDM 13.2 (12.0 – 14.6) 1st Degree Family History T2 DM ~ 1.5 – 3.0 Age 35 – 39 Years 1.25 (0.99 – 1.58) Age ≥ 40 Years 2.24 (1.26 – 3.98) Ethnicity: African American 1.75 (0.95 – 3.23) Hispanic 1.45 (0.87 – 2.41) Asian/PI 2.32 (1.52 – 3.54) Prior LGA Baby

Solomon C et al. JAMA 1997;278:1078-83; Kim et al. Am J Obstet Gynecol 2009;201:576.e1-6; Getahun D et al. Am J Obstet Gynecol. 2010;203:467.e1-6

Testing

Initial Visit

High-Risk for Glucose Intolerance Average-Risk for Glucose Intolerance First Visit:

  • A1c
  • 50 g 1 Hr Glucose Test
  • 75 g 2 Hr Glucose Test

24-28 Weeks:

  • 50 g 1 Hr Glucose Test
  • 75 g 2 Hr Glucose Test

First Visit Testing – A1c

Diagnosing Type 2 DM:

http://www.diabetes.org/diabetes-basics/diagnosis/?loc=DropDownDB-diagnosis O’Connor et al. Clin Chem Lab Med 2012;50(5):905-9.

A1c ≥ 6.5 DM2 A1c 5.7 – 6.5 Glucose Intolerance A1c < 5.7 Normal

Non- Pregnant 1st Trimester 2nd Trimester 3rd Trimester HbA1c % 4.8 – 5.5 (5.2) 4.3 – 5.4 (5.0) 4.4 – 5.4 (4.9) 4.7 – 5.7 (5.1) Average HbA1c Values Non-Diabetic Women

First Visit Testing – Diagnosing T2DM

A1c ≥ 6.5% Fasting plasma glucose ≥ 126 mg/dL (8-hour fast) 2-h plasma glucose ≥ 200 mg/dL following a 75 g

glucose load

Random blood glucose ≥ 200 mg/dL with

symptoms of hyperglycemia

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SLIDE 5
  • Testing for GDM
  • 1960s: Maternal risk for diabetes long-term
  • 2000s: Linear relationship between maternal

glycemia and pregnancy outcomes

Testing for GDM – Two Step Approach

Step 1 (screen): Non-Fasting 50 g 1 hr glucose test

≥ 130 mg/dL 23% screen positive ≥ 140 mg/dL 14% screen positive

Step 2 (diagnose): Fasting 100 g 3 hr glucose test

  • ≥ 2 abnormal values positive

Fasting (mg/dL) 1 hr (mg/dL) 2 hr (mg/dL) 3 hr (mg/dL) GDM Prevalence National Diabetes Data Group 105 190 165 145 3-4% Carpenter-Coustan Criteria 95 180 155 140 5-7%

IADPSG Consensus Panel. Diabetes Care. 2010;33(3):676-82.

Fasting 75 g 2 hr glucose test ≥ 1 abnormal value positive GDM prevalence ~ 20%

Testing for GDM – One Step Approach

VanDorsten et al. NIH Consens State Sci Statements. 2013;29(1):1-30.

Conclusion: 2 step approach Concerns raised:

Lack of evidence that more aggressive

diagnosis/treatment has benefit

Cost Resources Maternal Anxiety Overtreatment (cesarean rates)

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SLIDE 6
  • What We Do

Low Risk: 24 – 28 Weeks 50 g 1 hr < 140 mg/dL 50 g 1 hr > 140 mg/dL 100 g 3 hr FBG ≥ 95 1 hr ≥ 180 2 hr ≥ 155 3 hr ≥ 140 Abnormal Glucose Tolerance GDM High Risk: 1st Visit 50 g 1 hr Low Risk: Done High Risk: Repeat 24 – 28 Weeks Consider: A1c FBG 75 g 2 hr Type 2 DM 1 abnormal ≥ 2 abnormals

It depends:

Patient population Likelihood of follow-up Resources Future studies

How to Test? Overview

Physiology Testing

Pregnancy Outcomes

Treatment Pregnancy Management Postpartum Care

Pregnancy Outcomes in GDM

Among your patients with GDM, which adverse

  • utcome do you worry about the most?

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55% 15% 4% 26%

  • A. Shoulder dystocia
  • B. IUFD
  • C. Pre-eclampsia
  • D. Neonatal hypoglycemia
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SLIDE 7
  • Pregnancy Outcomes in GDM

Approximate Overall % Relative Risk/Odds Ratio Macrosomia 20 RR ~1.4 Pre-Eclampsia 15 RR ~1.7 Cesarean Section Varies RR ~ 1.2 Shoulder Dystocia 3-5 OR ~ 1.2 IUFD ~ 0.05 RR ~ 2

HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. Schmidt M et al. Diabetes Care. 2001;24(7):1151-5. Wendland E et al. BMC Pregnancy Childbirth. 2012;31(12):23-36.

Blinded study of ~25,000 women at 15 centers, 9 countries Primary predictor: Levels of hyperglycemia Primary outcomes: birthweight > 90%ile, primary CD, neonatal hypoglycemia, cord-blood C-peptide level > 90%ile

HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002.

Does hyperglycemia without overt diabetes during pregnancy increase risk of adverse pregnancy outcomes?

Level Fast 1 hr 2 hr 1 < 75 ≤ 100 ≤ 90 2 75-79 106-132 91-108 3 80-84 133-155 109-125 4 85-89 156-171 126-139 5 90-94 172-193 140-157 6 95-99 194-211 158-177 7 ≥ 100 ≥ 212 ≥ 178

HAPO Results

HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002. HAPO Study Cooperative Research Group. N Engl J Med. 2008;358(19):1991-2002.

HAPO Results

(~88 mg/dL) (165 mg/dL) (134.5 mg/dL)

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SLIDE 8
  • Macrosomia

What’s the Big Deal?

Weight Prolonged Labor (%) Excess Bleeding (%) CD (%) 3000 – 3999 g 0.9% 0.5 18 4000 – 4499 g 1.2 0.7 25.5 4500 – 4999 g 1.3 0.9 35.6 > 5000 g 1.5 1.1 50.6

Boulet SL et al. Am J Obstet Gynecol. 2003;188(5):1372-8; Acker et al. Obstet Gynecol. 1985;66:762; Nesbitt et al. Am J Obstet Gynecol. 1998;179:476; Sandmire et al. Int J Gynaecol Obstet. 1988;26:65; Overland E et al. Am J Obstet Gynecol. 2009;200(5):506

Maternal Risks

Weight Shoulder Dystocia Mechanical Ventilation > 30 min 5 min Apgar < 3 Neonatal Mortality ≤ 4000 g 0.6-3.7 % 4000 – 4449 g 4.9 – 23.1 % RR = 1.2 – 1.9 RR = 1.3-5.2 ≥ 5000 g 20-50 % RR = 4.0 RR = 5.2 RR = 2.7

Macrosomia – What’s the Big Deal?

Neonatal Risks

Other Risks:

  • Hypoglycemia
  • Hypothermia
  • Polycythemia
  • Birth trauma/asphyxia

Boulet SL et al. Am J Obstet Gynecol. 2003;188(5):1372-8; Acker et al. Obstet Gynecol. 1985;66:762; Nesbitt et al. Am J Obstet Gynecol. 1998;179:476; Sandmire et al. Int J Gynaecol Obstet. 1988;26:65; Overland E et al. Am J Obstet Gynecol. 2009;200(5):506

Overview

Physiology Testing Pregnancy Outcomes

Treatment

Pregnancy Management Postpartum Care

Sunday Monday Tuesday Wednesday Fasting 86 90 92 88 Post-Breakfast 156 148 138 144 Post-Lunch 119 150 108 133 Post-Dinner 144 101 138 139

38 year-old G1 at 30 wks. 75 g 2 hr: 88, 193, 168 (Normal: 92/180/ 153). Patient received dietary counseling, started logging sugars. Diet is appropriate. Several days of sugars reveals: What do you recommend?

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31% 44% 11% 4% 9%

A. Start Glyburide 2.5 mg before breakfast B. Continue diet, but reduce breakfast carbohydrates C. Start short-acting insulin before breakfast

  • D. Start a combination of short-acting and long-acting

insulin before breakfast E. None of the above

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SLIDE 9
  • Treatment of GDM

We know GDM impacts outcomes. Does treatment help?

Treatment of GDM – Crowther

Crowther et al. N Engl J Med. 2005;352:2477-86.

Intervention Group (%) Routine Care (%) Adjusted RR or Treatment Effect Adjusted p-value *Any serious perinatal complication 1 4 0.33 (0.14 – 0.75) 0.01 Admission to NICU 71 61 1.13 (1.03 – 1.23) 0.04 Macrosomia 10 21 0.47 (0.34 – 0.64) < 0.001 Neonatal hypoglycemia 7 5 1.42 (0.87 – 2.32) 0.16 Preeclampsia 12 18 0.7 (0.51 – 0.95) 0.02 Cesarean Delivery 31 32 0.97 (0.81 – 1.16) 0.73

* One or more of: death, shoulder dystocia, bone fracture, nerve palsy

Crowther et al. N Engl J Med. 2005;352:2477-86.

Treatment of GDM – Landon (NICHD)

Landon et al. N Eng J Med. 2009;361:1339-48.

Intervention Group (%) Control Group (%) Relative Risk p-value NICU Admission 9 11.6 0.77 (0.51 – 1.18) 0.19 Macrosomia 5.9 14.3 0.41 (0.26 – 0.66) < 0.001 Neonatal Hypoglycemia 5.3 6.8 0.77 (0.44 – 1.36) 0.32 Shoulder Dystocia 1.5 4.0 0.37 (0.14 – 0.97) 0.02 Cesarean Delivery 26.9 33.8 0.79 (0.64 – 0.99) 0.02 Preeclampsia or GHTN 8.6 13.6 0.63 (0.42 – 0.96) 0.01

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SLIDE 10
  • Dietary modification & exercise

Oral agents Insulin therapy Treatment of GDM

Treatment Improves Outcomes in Patients with GDM

No evidence to-date to support a

specific diet.

Carb-restriction (< 40%) seems to

improve outcomes

Usual advice: 25-30 kcal/kg/day, limit

carbs to < 40% of total calories, 20% protein, 40% fat.

Treatment of GDM – Diet

Han et al. Cochrane Database of Systematic Reviews 2013, Issue 3. Major et al. Obstet Gynecol 1998;91:600-4.

Exercise data is lacking with regards to pregnancy outcomes

Avoiding Ketosis

Severe carb restriction can result in ketosis – resulting from

breakdown of fatty acids in absence of sufficient carbohydrates

Ketosis may be associated with developmental abnormalities in

  • ffspring

Rizzo et al: Children’s developmental scores correlated inversely

with 3rd trimester beta-hydroxybutyrate levels

Onyeije et al: Maternal ketonuria associated with increased risk

  • f oligohydramnios, nonreactive NST, fetal heart rate

decelerations

Rizzo et al. N Engl J Med 1991;325:911-6. Onyeije et al. Am J Obstet Gynecol. 2001;184(4):713-8.

Glyburide (sulfonylurea) – Increases insulin release

from beta cells in pancreas

Metformin (biguanide) – Increases insulin sensitivity,

decreases gluconeogenesis

Treatment of GDM – Oral Agents

Caritis et al. Obstet Gynecol. 2013;121:1309-12.

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SLIDE 11
  • Langer: RCT of Glybruide vs Insulin

Glyburide

Langer et al. N Engl J Med 2000;343:1134-8. Langer et al. Am J Obstet Gynecol. 2005;192:134-9.

Variable/Outcome Glyburide (N = 201) Insulin (N = 203) P-value Mean Dose 9 ± 6 mg/day 85 ± 48 units/day Fasting Blood Glucose 98 ± 13 mg/dL 96 ± 16 mg/dL 0.17 Postprandial Blood Glucose 113 ± 22 mg/dL 112 ± 15 mg/dL 0.6 LGA 12% 13% 0.76 Neonatal hypoglycemia 9% 6% 0.25 Preeclampsia 6% 6% 1

Secondary analysis: No differences when stratified by disease severity.

Schwartz and colleagues: Glyburide crosses the placenta Rochon et al: Glyburide failure more common among patients with glucose challenge test ≥ 200 mg/dL. Jacobson: Patients treated with Glyburide had higher incidence of pre-eclampsia (12% vs 6%, p = 0.02) & neonates more likely to receive phototherapy (9% vs 5%, p = 0.046)

Schwartz et al. Abstract SMFM. Am J Obstet Gynecol 2003;S25. Rochon et al. Am J Obstet Gynecol. 2006;195:1090-4. Jacobson et al. Am J Obstet Gynecol. 2005;193:118-24.

Glyburide

Glyburide should be administered 30-60 minutes before a meal

Caritis et al. Obstet Gynecol. 2013;121:1309-12.

Glyburide – Timing of Administration Metformin

Rowan et al: RCT of Metformin vs. Insulin. Similar

pregnancy outcomes, 46% required supplemental insulin. Women preferred Metformin over insulin.

Moore: RCT of Metformin vs Glyburide. Generally similar

  • utcomes, but failure rate for metformin was 2.1 x higher

than Glyburide.

Rowan et al. N Engl J Med. 2008;358:2003-15. Moore et al. Obstet Gynecol. 2010;115:55-9.

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SLIDE 12
  • Insulin

Type Onset Peak (hours) Duration (hours) Insulin Lispro/Aspart 1-15 min 1-2 hrs 4-5 hrs NPH 1-3 hrs 5-7 hrs 13-18 hrs Insulin Glargine (Lantus) 1 hr None 24 hrs Insulin Detemir (Levemir) 1-2 hrs None 24 hrs

Overview

Physiology

Testing Pregnancy Outcomes Treatment

Pregnancy Management

Postpartum Care

Pregnancy Management Limited data to support any particular regimen for

surveillance

Well-controlled on diet alone: No additional

surveillance

Controlled on medication:

Twice weekly NSTs starting at 32 weeks Evaluation of fetal growth by ultrasound at ~36

weeks

Labor induction at 39 weeks

Induction of Labor

Rosenstein: Infant mortality rates at 39 weeks are lower than

  • verall mortality risk of expectant management.

Rosenstein et al. Am J Obstet Gynecol. 2012;206:309.e1-7.

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SLIDE 13
  • Overview

Physiology Testing Pregnancy Outcomes Treatment Pregnancy Management

Postpartum Care

Postpartum In-hospital:

Diet-controlled GDM: No further evaluation Medication-controlled: Fasting & postprandial

blood sugars x 1 day

6 week:

75 g 2 hr glucose test to assess for resolution Diet & exercise Strongly encourage highly-effective

contraception & preconception assessment for underlying diabetes

Recommend re-screening every 1-3 years

> 40% of women with GDM will develop type 2 diabetes

within 10 years

Postpartum screening rates are low (most studies < 50%)

Postpartum

Ratner et al. J Clin Endocrinol Metab 2008;93:4774.

Postpartum

Ratner et al. J Clin Endocrinol Metab 2008;93:4774.

Cumulative incidence of diabetes in the Diabetes Prevention Program by randomized treatment group in women with a history of GDM:

Intensive Lifestyle: Goal to achieve 7% reduction in weight via low-calorie, low- fat diet & moderate physical activity at least 150 minutes/week

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SLIDE 14
  • Patient-engagement in the process is potentially the most

important aspect of care

“Look, I'm on the poverty level. I might have $100, but I'm going to buy everything that's probably not good for me so that me and my kids can eat for the whole 30 days. I can't go down to Trader Joe's and bring home five things that are going to last us for 25 days. And see, people don't look at that. They don't look at your income ratio or none

  • f that. They just look at that you're not eating good.”

Conclusions

GDM represents a continuum of glucose intolerance Regardless of strategy for testing, aim to identify

chronic hyperglycemia as soon as it is present

Pregnancy outcomes depend on degree of glycemic

control

Patient engagement is critical for short and long

term outcomes

Questions?

SalmeenK@obgyn.ucsf.edu