advances in diabetes and pregnancy

International Diabetes CenterAdvances in Diabetes and Pregnancy... International Diabetes CenterGestational Diabetes • Part 1: Epidemiology, etiology and pathophysiology of diabetes –

International Diabetes Center

Advances in Diabetes and

Pregnancy

International Diabetes Center

Gestational Diabetes

• Part 1: Epidemiology, etiology and

pathophysiology of diabetes

– new classifications/definitions

– incidence, prevalence, morbidity and mortality

– causal factors associated with the development of GDM

– natural history

• Part 2: New therapeutic principles and

approaches from the perspective of SDM

– detecting the underlying defect

– determining the natural history

– matching therapy to defect

• Part 3: After GDM: the insulin resistance

syndrome

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Gestational Diabetes Mellitus

• Once believed to be a unimportant event in pregnancy

• Initially believed to be a predictor of type 2 diabetes, now

believed to be early type 2 diabetes

• A combination of increased insulin production with decreased

utilization due to insulin resistance

• Human placental lactogen production further exacerbates

insulin resistance

• Over nourishment of the fetus through “shunting”

• Maternal insulin does not pass placental barrier

• Excess fetal growth due in part to over stimulated fetal

pancreas

• Estimated to complicate 5% of all pregnancies

New

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Gestational Diabetes:

Epidemiology

0

20,000

40,000

60,000

80,000

100,000

120,000

140,000

160,000

GDM

cases

undetected

morbidity-poor control

morbidity-tight control

International Diabetes Center

Screening and Diagnostic Criteria

for GDM

SCREENING

• 50 gram Glucose Challenge Test

– 1 hour > 140 mg/dL (7.8 mmol/L)

DIAGNOSIS

• 100 gram Oral Glucose Tolerance Test (OGTT)

– Fasting > 95 mg/dL (5.3 mmol/L)

– 1 hour > 180 mg/dL (10.0 mmol/L)

– 2 hour > 155 mg/dL (8.6 mmol/L)

– 3 hour > 140 mg/dL (7.8 mmol/L)

• 75 gram Oral Glucose Tolerance Test

– Fasting > 95 mg/dL (5.3 mmol/L)

– 2 hour > 140 mg/dL (7.8 mmol/L)

• One abnormal value ?

International Diabetes Center

Natural History of Gestational Diabetes

0 50 100

150

200

250

300

del

50 100

150

Weeks

Insulin Resistance

Insulin Level

Fasting Glucose

Post Meal Glucose

At risk for GDM

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GCT OGTT

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Insulin Resistance (Due to HPL or

Underlying Type 2 Diabetes)

Insulin Sensitive Cells

Nucleus

G G G

G

G

G G G G

G G

G G G

G

G G G G

G G

G

Insulin Glucose

Insulin Receptor

Glucose Transporter (GLUT 4)

G

HLP

G G

G

G G G G

G G

G

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Diabetes Therapies: matching action to underlying defect

Medical Nutrition Therapy

Oral Agents

– Insulin Secretegogues

Insulin

– Bolus/pre-meal insulin (Regular, Lispro, Aspart)

– Basal/background insulin (NPH, Lente, Ultralente, Glargine)

New

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Medical Nutrition Therapy*

• Action

– Emphasis on BG control, not

weight loss

– Carbohydrate counting

– Prevention of weight gain in

obese women

– Increased physical activity

• Clinical Indicators

– Insulin Deficiency / Insulin

Resistance

– BMI - no range

– BG range <120 mg/dL (6.7

mmol/L) if used as monotherapy

– Always used as an adjunct therapy

with pharmacological agents

• Side effects

– None

• Precautions and Contraindications

– Kidney Disease : low protein diet for macroalbuminuria

– Liver Disease : none

– Heart Disease : assess fitness before initiating activity program

• Pregnancy

– Alter diet and activity to promote normal fetal development and avoid fetal and maternal stress

*Self-monitoring of blood glucose and urine ketones (R/O starvation) are essential components of MNT

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SDM GDM Master DecisionPath

Overview

Fasting < 95 mg/dL

(5.3 mmol/L)

Casual < 120 mg/dL

(6.7 mmol/L)

Fasting < 95 mg/dL

(5.3 mmol/L)

Casual < 120 mg/dL

(6.7 mmol/L)

Medical Nutrition Stage

Focus on carbohydrate foods (portions

and number/meal) Encourage physical activity/exercise

Medical Nutrition Stage

Focus on carbohydrate foods (portions

and number/meal) Encourage physical activity/exercise

30 mg/dL (1.7 mmol/L)

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Insulin Secretagogues: Glyburide

• Action

– Release of insulin from

pancreas in response to a glucose challenge

• Clinical Indicators

– Insulin Deficiency

– *Mean BG <150 mg/Dl (8.3

mmol/L) – *High postprandial BG 120 –

180 mg/dL (6.7-10.0 mmol/L)

• Side effects

– Weight gain

– Hypoglycemia

• Precautions and

Contraindications

– Kidney Disease: SU-use caution;

– Liver Disease: Use caution, not well studied with liver disease

– Known hypersensitivity to the drug

• Pregnancy

– All other oral agents pass the placental barrier

New

*Label indicates average glucose lowering 60 mg/dL (3.3 mmol/L)

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Beta cells produce insulin and

store it in secretory vesicles

ATP ADP

Pyruvate

Voltage-gated Calcium Channel

Ca++

Ca++

G

G G

G

G G

Glucose Transporter (Glut 2) G

G G

G

G G

Potassium Channel

K +

Insulin Secretagogues: Beta Cell

Function

G

K +

K+ Channel Blocked- membrane becomes depolarized

X

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SDM GDM Master DecisionPath

Overview

Fasting < 95 mg/dL

(5.3 mmol/L)

Casual < 120 mg/dL

(6.7 mmol/L)

Fasting < 95 mg/dL

(5.3 mmol/L)

Casual < 120 mg/dL

(6.7 mmol/L)

HbA1c NA

Medical Nutrition Stage 1.7 mmol/L30 mg/dL

Oral Agent Stage

Fasting > 95 mg/dL

(5.3 mmol/L)

Casual > 120 mg/dL

(6.7 mmol/L)

Fasting > 95 mg/dL

(5.3 mmol/L)

Casual > 120 mg/dL

(6.7 mmol/L)

HbA1c NA

Insulin Deficiency Glyburide

BG

60 mg/dL

3.3 mmol/L

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Insulin

• Action

– Compensates for diminished

beta cell secretion of insulin

– Overcomes insulin resistance in

peripheral tissue

– Suppresses gluconeogenesis

• Clinical Indicators

– Insulin Deficiency / Insulin

Resistance

– BMI-no specific range

– HbA1c N.A

– FPG >95 mg/dL (5.3 mmol/L)

– CPG >120 mg/dL (6.7 mmol/L)

• Side effects

– Hypoglycemia – Weight gain

• Precautions and

Contraindications

– Kidney Disease : none

– Liver Disease : none

– Heart Disease : none

• Pregnancy

– Therapy of choice in GDM when FPG is high, when HbA1c >8% or uncertain of type 1 diabetes

International Diabetes Center

0

10

20

30

40

50

Normal Insulin Secretion

Time (Hours)

Basal Insulin Needs

Bolus insulin needs

SDM GDM Master DecisionPath

Overview

Oral Agent Stage Glyburide

Oral Agent Stage Glyburide

Fasting < 95 mg/dL

(5.6 mmol/L)

Casual < 120 mg/dL

(6.7 mmol/L)

Fasting < 95 mg/dL

(5.6 mmol/L)

Casual < 120 mg/dL

(6.7 mmol/L) Medical Nutrition Stage

Fasting >95 mg/dL

(5.6 mmol/L)

Casual > 120 mg/dL

(6.7 mmol/L)

Fasting >95 mg/dL

(5.6 mmol/L)

Casual > 120 mg/dL

(6.7 mmol/L)

HbA1c NA

Note: Each stage

requires a pre-set

target and a

timeline to reach

that goal

Insulin Stage

Physiologic Insulin Stage 4

RA-RA-RA-N Conventional Insulin Stages 2 or 3

30 mg/dL

1.7 mmol/L

60 mg/dL

3.3 mmol/L

>60 mg/dL

>3.3 mmol/L

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GDM, Type 2 Diabetes and

Metabolic Syndrome

•Is GDM really type 2 diabetes in

pregnancy?

after pregnancy?