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CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXIC PowerPoint Presentation
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CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXIC

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CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXIC - PowerPoint PPT Presentation


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CURRENT CONCEPTS DIABETES IN PREGNANCY DIANA CLOKEY MSRD,RPH,CDE SCHOOL OF MEDICINE/DEPT OB/GYN UNIVERSITY OF NEW MEXICO. OBJECTIVES . Understanding pathophysiology of fetal and neonatal complications in pregnancy Discuss the diagnosis and management of gestational diabetes mellitus

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slide1

CURRENT CONCEPTS

DIABETES IN PREGNANCY

DIANA CLOKEY MSRD,RPH,CDE

SCHOOL OF MEDICINE/DEPT OB/GYN

UNIVERSITY OF NEW MEXICO

objectives
OBJECTIVES
  • Understanding pathophysiology of fetal and neonatal complications in pregnancy
  • Discuss the diagnosis and management of gestational diabetes mellitus
  • Understanding the pharmacology of the different insulin/oral hypoglycemic agents
  • Introduce on going research in the field of Diabetes in Pregnancy
incidence of diabetes in pregnancy
INCIDENCE OF DIABETES IN PREGNANCY

- Incidence in all pregnancies 7%

  • 80-90% of patients with diabetes complicating pregnancy have gestational diabetes. 200,000 cases annually
  • 10-20% of patients with diabetes complicating pregnancy have pre-existing (Type 1 and Type 2)
both gdm and type 2 are heterogeneous disorders
BOTH GDM AND TYPE 2 ARE HETEROGENEOUS DISORDERS

Pathophysiology is characterized by

- peripheral insulin resistance

- Impaired regulation of hepatic glucose production

- Chronic hyperinsulinemia or impaired beta cell secretion

- Auto antibodies presents 10-30% of GDM

- Single gene mutation (MODY 2) ~ 10% cases of GDM

epidemiology
Epidemiology
  • Incidence of GDM has increased across all ethnic groups
  • Increase of GDM in younger women
  • Parallels obesity epidemic
  • Maternal obesity strongly linked to excessive birth weight
definition of gdm
DEFINITION OF GDM

Any degree of glucose intolerance with onset or first recognition during pregnancy

Diabetes Care January 2004

adverse effects in offspring
Conception of 8th week

Malformations: A1C>10 Caudal regression (3wk) NTD (4 wks) Cardiac (5 wks) Renal (5 wks) GI (6 wks )

8th week to delivery Chronic hypoxia Intrauterine death Hyperinsulinism Macrosomia Organomegaly Polyhydraminos

RDS

ADVERSE EFFECTS IN OFFSPRING
long term effects in children
LONG – TERM EFFECTS IN CHILDREN

- Obesity

- Abnormal glucose tolerance

- neurospychological defects

diabetes effect on the pregnancy
DIABETES EFFECT ON THE PREGNANCY
  • Dystocia
  • Preeclampsia
  • Pyelonephritis
  • Pelvic trauma
  • C-section
screening strategy
SCREENING STRATEGY
  • Risk assessment for GDM at first prenatal visit

Low Risk

Average Risk

High Risk

low risk status requires no glucose testing
LOW RISK STATUS (requires no glucose testing)
  • Age < 25
  • Weight normal before pregnancy
  • Member of an ethnic group with low prevalence of GDM
  • No known diabetes in first-degree relatives
  • No history of abnormal glucose tolerance
  • No history of poor obstetric outcome
  • Normal birthweight of mother

(2500-4400 grams)

Petitt Diabetes Care 21 : B 138 1998

average risk
Average Risk
  • Two–step approach
  • 24 – 28 wks
  • 1 hr 50 gram – no fasting necessary
  • Venous plasma (≤140 mg/d1) identifies 80% of women with GDM. A value > 130mg/d1 identifies 90% of women with GDM
  • 3hr GTT if patient fails screen
high risk
HIGH RISK
  • Prior GDM, obesity, advanced maternal age, non-white ethnicity
  • Perform blood glucose test as soon as feasible
  • One step approach (75gm 2h GTT)
  • Repeat at 24–28 wk if needed
control of maternal glycemia target glucose levels
Fasting

Preprandial

1 hr after meals

2 hr after meals

30-90 mg/d1

60-105 mg/d1

<140 mg/d1

<120 mg/d1;

CONTROL OF MATERNAL GLYCEMIA (TARGET GLUCOSE LEVELS)
  • Avoid hypoglycemic <60mg/dl
  • PP measurements timed from start of
  • meals
medical nutrition therapy mnt
MEDICAL NUTRITION THERAPY (MNT)
  • MNT is the cornerstone of treatment – It is the only therapy for 40-85% of women with GDM
  • Goal: To provide calories and nutrients to sustain pregnancy with appropriate weight gain normoglycemcia and the absence of ketones

Metzger Be etal Diabetes Care August 1998

dietary recommendations
DIETARY RECOMMENDATIONS

- Composition of diet 40% CHO, 20% PRO, 40%/fat

- Post prandial glucose should guide CHO intake

- CHO should be distributed throughout the day in small frequent meals

  • NO changes in calorie intake
  • Recommend use of maternal weight gain grids
  • Reaffirmed safety of non-nutritive sweetners
great variabilty in daily energy intake for pregnancy range from 1500 2800kcal d
GREAT VARIABILTY IN DAILY ENERGY INTAKE FOR PREGNANCY RANGE FROM 1500-2800KCAL/d
  • FOR GDM – underweight and normal weight woman should maintain energy intake to support adequate not excessive weight gain
  • Suggested range 30-35 kcal / kg IBW or PBW
  • Starting in 2nd + 3rd trimester ½ - 1 # per week
management of obese gdm women
- Avoid severe calorie restriction less than 1500kcal

- 33 % calorie restriction 1600-1800-kcal provides improved glucose control and negative for ketones. Recommendation 24/kcal/kg

- Avoid ketonuria or ketonemia

children’s mental development-index-score and average Standford–Binet scores correlated inversely with 3rd trimester B-hydroxybutyrate

MANAGEMENT OF OBESE GDM WOMEN

Knopp RH et ak J.AM Col Nutr.1991

nutrition practice guidelines states
NUTRITION PRACTICE GUIDELINES STATES:
  • Calorie requirements are monitored by following weight gain patterns urine ketone testing, assessing appetite and review food records.

American Dietetic Ass. 1995

nutrition guidelines
NUTRITION GUIDELINES
  • Carbohydrate counting/Label reading
  • CHO restriction at breakfast
  • Avoid sugar, concentrated sweets, refined/ processed starches
  • Eliminate liquid CHO (juices), test milk
  • FDA has approved aspartame (Equal) sucralose (splenda), saccharine (sweet n low) for pregnancy
  • Encourage high fiber foods
carbohydrate budget
CARBOHYDRATE BUDGET

Breakfast 1-2 carbohydrate Choices

Lunch 3-4 carbohydrate Choices

Supper 3-4 carbohydrate Choices

Snack (1-3) 1-2carbohydrate Choices

Amount of CHO typically found in a 1800-2400 calorie diet

role of physical activity
ROLE OF PHYSICAL ACTIVITY

Women who are physically active before and in early pregnancy have a lower rate of GDM

  • 48-76% reduction in incidence of GDM
  • Acute effects is to lower BG 23mg/dl
  • Less or no use of medication

Dempsey JC. Etal Diabetes Res Clinical practice 2004

Avory MD etal J. Met-Fer Med 2001

safe exercise
SAFE EXERCISE
  • Monitor fetal activity and BG before and after exercise
  • Limit to light to moderate activity 15-30 minutes
  • Upper extremity exercise produces no uterine contractions
  • 3 episodes/wk> 15 minutes
  • No recommendations regarding type of exercise
glucose monitoring
GLUCOSE MONITORING
  • Daily SMBG superior to intermittent monitoring
  • Fasting blood sugar most predictive of fetal demise
  • Post prandial sugars most predictive of macrosomia
  • GDM and Type 2 (test FBS and 2 hpp) Type 1 (FBS pre and post meals)
  • Allows patient flexibility in food choices
ketone urine testing
KETONE URINE TESTING
  • Pre-breakfast urine testing to detect starvation ketosis
  • Illness
  • Blood glucose over 200 mg/dl
criteria to begin concurrent therapy
CRITERIA TO BEGIN CONCURRENT THERAPY

- When following diet, 20% above normal values are outside targets range

- When nutritional parameters are compromised

      • Wt loss
      • Restriction of healthy foods
      • Nutritional adequacy
      • Ketones
  • Fetal abdominal circumference > 70%

(u/s in early 3rd trimester)

pharmacotherapy
PHARMACOTHERAPY

- insulin

- oral hypoglycemic agents

drug category in pregnancy
DRUG CATEGORY IN PREGNANCY

A Well controlled human studies, no risk to fetus

B Animal studies no risk to fetus, no well controlled studies in pregnant women

CAnimal studies have shown adverse effects. No well controlled studies in pregnant women Potential benefits may warrant use despite potential risk

out with the old insulins no longer produced
OUT WITH THE OLD.... INSULINS NO LONGER PRODUCED

- Regular pork

insulin

- NPH pork insulin

- Ultralente

- Lente

today s insulin biosynthetic human insulin
TODAY’S INSULIN(BIOSYNTHETIC HUMAN INSULIN)

- Fast acting analogs

- Short acting regular

- Intermediate acting NPH

- Long acting glargine (Lantus)

insulin use
INSULIN USE
  • Human insulin is advocated to minimize the transplacental transport of anti-insulin antibodies
  • Rapid acting analogs preferable to Regular insulin
  • NPH insulin is the basal insulin of choice
  • No data demonstrating the superiority of any particular insulin regimen.
lispro humalog in pregnancy
LISPRO (HUMALOG) IN PREGNANCY
  • Antibody formation comparable to regular human insulin
  • Not detectable in cord blood
  • Similar or improved metabolic control
  • Less hypoglycemia
  • Enhanced patient satisfaction
  • ? Progression of diabetic retinopathy
new insulins now available
NEW INSULINS NOW AVAILABLE

- Glulysine (Apidra)

Fast acting analog

- Detemir (Levemir)

- Category C

- long acting basal. Given twice/d

- flat peakless concentration/time profile

- Inhaled Insulin (Exubera)

- used only for control of glucose after meals

- dispense in 1mg(3u) or 3mg (8u).

- may affect lung function.

Contraindicated smokers; chronic lung disease

- Cost 3-4 x more than injectables

beware of vicious cycle
BEWARE OF VICIOUS CYCLE

Increased Appetite

Wt Gain

Insulin resistance

oral hypoglycemia agents
ORAL HYPOGLYCEMIA AGENTS
  • Glyburide vs. insulin (Langer NEJM 2000)
  • Similar levels of glycemic control
  • Acceptable alternative therapy to insulin if lifestyle fails
  • Obese and severely hyperglycemic women need closer follow-up
oral hypoglycemia agents39
ORAL HYPOGLYCEMIA AGENTS

Glyburide (cat B)

- Most effect with/slightly increased BW

- Crosses placenta in very low levels

- t½ 3-5h, peaks 2.75h

- Best timing 1 hour before meal

- Failure rate 20-30%

-Failure rate when started < 30wks

FBS > 110 and 1 hour BG > 140

slide40
Biguanides (Metformin) (Cat B)

- Utilized for insulin resistance & PCOS

- Insulin sensitizer

- Small molecule – crosses the placenta

- Long – term studies are now in progress

(MiG study)

- No evidence teratogenesis

- MiG TOFU (the offspring follow up)

Can J Clinical Pharmacol. 2003; 10(4):179-183

slide41
Glucosidase inhibitor (acarbose)

- Category B

- Promising

- Not absorbed systemically

- Recommendation is to start at low doses

due to GI effects

- Can only treat hypoglycemia with

glucose

slide42
Thiazolidineones (TZDs)

- Category C

- Crosses placenta levels of ½ the

maternal blood level

- No data in fetal safety

- Depends on insulin release in mother

- Has not been studied in pregnancy

exanatide glp 1 agonist
Exanatide (GLP-1 Agonist)
  • Category C
  • Byetta
  • Injection
  • Depends on insulin release in mother
  • Has not been studied in pregnancy
obstetrical management
Obstetrical Management
  • Fetal kick counts (32-32 weeks gestation)
  • NST’s/AFI’s begin at 32 weeks gestation for pre-existing and A2 GDM
  • Ultrasound for growth
population perspective
POPULATION PERSPECTIVE
  • GDM identifies younger women with glucose levels in the upper end of the population distribution during pregnancy. They may

- never get diabetes

- on their way to diabetes

- already have diabetes

post partum
POST PARTUM

- 75g 2h OGTT at 6 weeks

- Counseling and education

- Recommend test one year after

delivery then every 3 years

(12% conversion rate 1 year; 50-60%

conversion in 5-10 years)

breast feeding and gdm
BREAST FEEDING AND GDM
  • Very limited data specific to GDM
  • Associated with lower rates of type 2 diabetes and reduced CHD risk in general population
  • Greatest protection > 6 months)
  • Glyburide/glipizide not found in breast milk
hapo study hyperglycemia and adverse pregnancy outcome
HAPO STUDY Hyperglycemia and Adverse Pregnancy Outcome
  • Summary and Recommendations from 3rd International Workshop Conference on GDM: 1990
  • “With respect to GDM, the heart of the matter is the relationship between the degree of glucose intolerance and or hyperglycemia and the risk of adverse maternal, fetal and neonatal outcomes. The highest priority should be given to efforts to develop international consensus on methods and definitions.”
hapo study design
HAPO- STUDY DESIGN

- Multicenter observational study of the association between maternal hyperglycemia and perinatal outcome

  • Investigator initiated
  • Tests no interventions- “not a clinical trial”
  • Will not answer treatment of diabetes
hapo study design why do it
HAPO STUDY DESIGN: “WHY DO IT?”
  • Overt diabetes clearly increase the risk of adverse pregnancy outcome
  • A critical question remains: What level of glucose intolerance short of diabetes increase the risk of adverse pregnancy outcome?

- Threshold vs continuum

- If continuum, setting the cut points

hapo study hypothesis
HAPO STUDY HYPOTHESIS

Hyperglycemia in pregnancy, less severe than overt DM, is associated with increased risk of adverse maternal, fetal and neonatal outcomes that is independently related to the degree of metabolic disturbance

hapo study design what is it
HAPO STUDY DESIGN: WHAT IS IT?
  • Observational study
  • Double blinded
  • 15 field centers in 9 countries
  • 25,000 subject enrolled in 5-6 years
  • Populations to be studied Caucasians, Black, Latino, Asian (Thai)
hapo study endpoints
HAPO STUDY ENDPOINTS

Relationship between maternal hyperglycemia and rates of:

  • Cesarean delivery
  • Macrosomia or LGA babies
  • Fetal hyperinsulinemia
  • Neonatal “obesity” (skinfold thickness)
  • Neonatal hypoglycemia
  • Other morbidites
summary
SUMMARY

In the next few years we can expect.....

  • Uniform outcome based diagnostic criteria for GDM
  • Further research in determining safety and efficacy of oral hypoglycemic agents/insulins in mother and fetus
  • Further research on the off-spring of women with diabetes during pregnancy
  • Revision of IOM recommendations for pregnancy
references
REFERENCES
  • 5TH International Workshop in GDM, November 2005, Chicago
  • ACOG Practice Bulletin vol.105 No 3, March 2005
  • Diabetes Care vol 27 January 2004