What is Gestational Diabetes Mellitus (GDM)? 2

- Glucose intolerance with onset or first recognition - Insufficient pancreatic Beta-cell function

- Insulin resistance (most common) - Auto-immune disease (less common) - Monogenic causes (single gene defect, rare)

Lecture 20: Gestational Diabetes Flashcards by Jose Rosas

What is Gestational Diabetes Mellitus (GDM)?

Glucose intolerance with onset or first recognition

- Insufficient pancreatic Beta-cell function

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If a women who has a history of GDM, she is more likely to have worsen effects when pregnant.
T/F

True

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Most, but not all women with GDM will develop diabetes ______ of pregnancy

outside

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GDM is caused by?

Insulin resistance (most common)
Auto-immune disease (less common)
Monogenic causes (single gene defect, rare)

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What are 2 reasons for the rise in GDM?

Increased screening during pregnancy

- Changes in diagnostic criteria

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What explanations because of increased screening?

More women are being screened

- Undiagnosed diabetes is being diagnosed first in pregnancy

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What was the mean GDM percentage in 1991?

What is the mean GDM percentage in 2000?

- 6.9

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Blood glucose homeostasis is maintained within the ____ ______.

Narrow Range

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What is the normal range when fasting?

70-100mg/100ml or (3.9-5.5mmol/L)

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What happens during Hypoglycermia when it is less than 2.5 mmol/L? (4)

Confusion, Drowsiness, Coma, Seizure

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What happens during Hypoglycemia when it is less than 2.7 mmol/L? (7)

Nervousness, Sweating, Intense Hunger, Trembling, Weakness, Irregular Heart Rate, Difficulty Speaking

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What happens during Hyperglycemia when it is greater than 14 mmol/L? (5)

Frequent Urination, Sugar in Urine, Frequent Thirst and Hunger, Ketoacidosis, Coma

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Insulin is the only hormone capable of:

lowering blood glucose

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Actions of insulin lowering blood glucose

Promotes cellular uptake of glucose form the blood
Promotes energy storage
Promotes utilization for energy production

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Which cells in the Islets of Langerhans sense blood glucose levels?

Pancreatic Beta Cells

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When Blood glucose rises, Pancreatic Beta-cells:

Secrete insulin into systemic circulation

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Starting with the uptake of glucose by the _____ transporter, the phosphorylation of glucose causes a rise in the ___:___ ratio

GLUT2

ATP; ADP

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The rise in the ATP:ADP ratio ______ the potassium channel that _________ the membrane, causing the ______ channel to ____ up allowing calcium ions to flow ____.

inactivates
depolarizes
calcium
open
inward

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The ensuing rise in levels of _____ leads to the ______ of insulin from storage _______

Calcium
exocytosis
granules

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Insulin Structure

Insulin is a _____ hormone derived from ____

peptide; proinsulin

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Insulin Structure

_-_______ is cleaved off during processing and packaged along with _____ in storage granules

C-Peptide

Insulin

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Insulin Structure

C-peptide is _____ along with insulin from _______ ____-______.

released

Pancreatic Beta-Cells

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This muscle is the principal site of whole-body glucose disposal

Skeletal

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Less_____ is transported into _____ tissue than into _____ muscle but ____ is still an important tissue for glucose uptake

Glucose, adipose, skeletal, adipose

This is the main insulin-responsive glucose transporter

GLUT-4

GLUT 4 is both expressed in skeletal muscle and adipose | T/F

True

When insulin levels are low, GLUT-4 is stored in

Intracellular Vesicles

Insulin-Stimulated Glucose Uptake | _____ is stored in intracellular vesicles.

GLUT-4

Insulin-stimulated Glucose Uptake Insulin binds to the _______ domain of its receptor in the _____ membrane, resulting in ______ of _____ portion of the receptor (a _____ kinase)

``` extracellular plasma phosphorylation intracellular Tyrosine ```

Insulin-stimulated Glucose Uptake | The activated ____ kinase phosphorylates insulin-receptor _______ such as the ___ molecules

Tyrosine substrates IRS

What are the IRS molecules being referred to ?

IRS-1 IRS-2 IRS-3 IRS-4

Insulin-stimulated Glucose Uptake These insulin-receptor substrates form ______ with docking _____ such as ______ at its regulatory ___ by means of ___ domains

complexes proteins; PI-3K p85 SH2

Insulin-stimulated Glucose Uptake | ____ is the constitutively bound to the catalytic subunit (____)

p85 | p110

Insulin-stimulated Glucose Uptake | Activated of ____ is a major pathway in the mediation of insulin stimulated glucose transport and metabolism

PI-3K

PI-3K activates _______-______ kinases that participate in the activation of _____ ______ _ and typical forms of _____ _____ _____

phosphoinositide-dependent protein kinase B protein kinase C

Protein kinase B is aka? | Protein kinase C is aka?

- Akt | - PKC

Insulin-stimulated Glucose Uptake ____ stimulates glucose transport by pathways that are independent of _______ kinase and that may involve ________activated kinase

Exercise phosphoinositide-3 5'-AMP

When is the Oral Glucose Tolerance Test used on pregnant women?

24th-28th week (end of second trimester)

What does the Oral Glucose Tolerance Test do?

- measure levels of glucose in the mother's blood following ingestion of sugary drink (100g dextrose) - abnormal levels may indicate gestational diabetes

Postpartum blood glucose in GDM group was ____ to pregnant controls (______ insulin action resolves with delivery of baby)

similar | inadequate

Normal Glucose Regulation during Pregnancy Normal pregnancy is characterized by _____ decrease in insulin mediated glucose uptake and a ___-____ increase in insulin secretion to maintain _____ in pregnant mothers

50% 200-250% euglycermia (normal blood glucose levels)

Progressive insulin resistance begins near mid-pregnancy and progresses through the _____ trimester to levels that are approximate insulin resistance seen in ___-__ ________.

- third | - Type-2 Diabetes

Pancreatic Beta-cells normally ______ insulin secretion to compensate for _____ resistance of pregnancy

increase | insulin

Normal Glucose Regulation during Pregnancy changes in circulating _____ levels over a course of pregnancy are quite _____ compared with ____ changes in insulin sensitivity.

glucose small large

Insulin Resistance may be due to: | 2

- increased maternal adiposity | - Insulin-desensitizing effects of placental hormones

What is an example of placental hormones?

Human placental lacotgen or human chorionic somatomammotropin

Rapid abatement of insulin resistance after delivery suggests:

Major contribution from placental hormones

Abnormal Glucose Regulation with GDM Insulin secretion is ____ to compensate for the insulin resistance, leading to _______ that is detected by routine glucose screening in pregnancy

inadequate | hyperglycemia

Abnormal Glucose Regulation with GDM | Gestational diabetes results from:

inability of pancreatic Beta-cells to make enough insulin

Increased insulin resistance with GDM | Glucose Infusion Rate (GIR) is ____ in pregnant women than in women with _____

higher | GDM

``` Increased Insulin Resistance with GDM Lower GIR (__-__%) in women with GDM indicates ____ glucose uptake and _____ insulin resistance ```

30-40 less more

Women who had GDM will have less insulin resistance post partum. T/F

False, they will have more

What are some risk factors for GDM? | which one is not a modifiable risk factor

- Obesity - Physical inactivity - Diet in Saturated Fat - Smoking - Advance Maternal Age - Family history of Diabetes (not modifiable)

What are some ways obesity increases risk of GDM?

- Increased Circulating levels of leptin - increased inflammatory marker TNF-alpha and C-reactive protein - Decreased levels of adiponectin - Increased fat in liver and muscles - Abnormal sub-cellular localization of GLUT4 transporters

What are some treatments in GD?

- Low-carb diet - Exercise - Maintain healthy pregnancy weight - Monitor glucose levels - If necessary, take daily insulin injections

What are some risks to the offspring of GDM mothers?

- Greater birth weight (macrosomia) - Obesity - Increased of Type 2 diabetes

____ is the most important risk factor for development of _________ in youth

Obesity | Type 2 diabetes

_____ has led to dramatic _____ type 2 diabetes among _____ and _____ over the past 2 decades

Obesity increase youth; adolescents