Exam 4 - Gestational Diabetes Flashcards
What is gestational diabetes?
glucose intolerance with onset or first recognition during pregnancy
characterized by insufficient pancreatic B-cell function to meet the body’s insulin needs
What is insulin resistance like before and after pregnancy for women who have gestational diabetes?
Insulin resistance exists before pregnancy in women with history of GDM but worsens during gestation
Most women with GDM go on to develop diabetes outside of pregnancy
What might gestational diabetes be caused by?
insulin resistance (progression to Type 2 Diabetes, most common form)
autoimmune disease (progression to Type 1 Diabetes, less common)
monogenic causes (single gene defects, very rare)
How has the incidence of gestational diabetes changed over the last 6-8 years?
it has doubled and is paralleling the obesity epidemic
What are possible explanations for the rise in GDM?
increased screening (more women being screened, and undiagnosed diabetes is first found in pregnancy)
changes in diagnostic criteria (changed in the 1990s resulting in inclusion of more women)
What was the mean GDM in 1991 and 2000?
1991 - 5.1%
2000 - 6.9%
What is normal range for fasting glucose? What ranges determine hypoglycemia and hyperglycemia?
70-99 mg/100 ml, or 3.9-5.5 mmol/L
hypoglycemia: <2.7 mmol/L
hyperglycemia: >14 mmol/L
What symptoms can happen with hyperglycemia, hypoglycemia, and severe hypoglycemia?
hyperglycemia: frequent urination, sugar in urine, frequent thirst and hunger, ketoacidosis, and coma
hypoglycemia: nervousness, sweating, intense hunger, trembling, weakness, irregular heart rate, and difficulty speaking
severe hypo: confusion, drowsiness, coma, and seizure
What factors increase blood glucose to maintain homeostasis?
diet (absorption from digestive tract)
mobilization (hepatic glucose production through glycogenolysis and gluconeogenesis)
What factors decrease blood glucose to maintain homeostasis?
utilization/storage (utilize for energy production or store through glycogenesis or triglycerides)
excretion (unusual, only excreted through urine and blood glucose is so high that it exceeds the reabsorptive capacity of the kidney tubules)
What are the 3 basic functions of insulin in maintaining blood glucose homeostasis?
promote cellular uptake of glucose from the blood
promotes energy storage
promotes utilization for energy production
What body structures are involved in insulin release?
pancreatic B-cells in the islets of Langerhans sense blood glucose levels
when blood glucose rises, the B-cells secrete insulin into the systemic circulation
Describe the process of glucose stimulated insulin release (on a cellular level)
- glucose flows down its concentration gradient into the B-cell through a GLUT2 transporter
- phosphorylation of glucose causes a rise in the ATP:ADP ratio
- rise in ratio inactivates the potassium channels
- membrane polarizes, opening the voltage gated calcium channel
- calcium ions flow in
- rise in calcium triggers exocytosis of insulin from storage granules
Describe the structure of insulin
peptide hormone, derived from proinsulin
C peptide is cleaved off during processing, and it remains with insulin in the storage granules and when it is released from the B-cells
Where does most glucose uptake occur?
mostly in skeletal muscle, but adipose tissue is also important
Where is GLUT4 when insulin levels are low?
stored in intracellular vesicles
Describe the process of insulin stimulated glucose uptake (on a cellular level)
- GLUT-4 is stored in intracellular vesicles.
- Insulin binds to extracellular part of receptor in the plasma membrane, causing phosphorylation of the
intracellular portion (a tyrosine kinase). - activated tyrosine kinase phosphorylates insulin-receptor substrates (IRS)
- insulin-receptor substrates form complexes with docking proteins such as phosphoinositide-3 kinase (PI-3K) at its regulatory 85-kd subunit (p85)
- p85 binds to the catalytic subunit (p110)
- Activation of PI-3K phosphorylates membrane-bound phosphoinositol-3,4,5-phosphate (PIP3)
- PIP3 activates phosphoinositide-dependent kinases that activate protein kinase B (also known as Akt) and atypical forms of protein kinase C (PKC)
- GLUT-4 is translocated to cell membrane, where it can facilitate glucose uptake
GLUT4 vs. GLUT2
GLUT2 is how glucose enters the pancreatic B-cells to trigger insulin release
GLUT4 is how glucose enters the skeletal muscle/adipose cells during insulin stimulated glucose uptake
How does exercise affect glucose uptake?
Exercise stimulates glucose transport by pathways that are independent of phosphoinositide-3 kinase and that may involve 5’-AMP–activated kinase
How is GDM diagnosed? Describe the test and normal vs abnormal responses?
oral glucose test in the 24-28th weeks of pregnancy
measures the level of glucose in the mother’s blood following the ingestion of a sugary drink containing 100 g of dextrose
In GDM patients, the blood glucose is significantly higher at 1, 2, and 3 hours than in the non-GDM patients. In normal results, the blood glucose should return to the fasting level after about 3 hours, but in GDM patients the glucose was still significantly elevated.
How is euglycemia achieved in non-GDM pregnant women?
50% decrease in insulin-mediated glucose uptake byt a 200-250% increase in insulin secretion to maintain euglycemia
What factors may cause insulin resistance and increased insulin secretion in a non-GDM pregnancy?
insulin resistance:
- increased maternal adiposity
- insulin desensitizing effects of placental hormones (like human placental lactogen and human placental growth hormone) which is likely because insulin resistance resolves rapidly after delivery
increased insulin secretion:
- pancreatic B-cells increase secretion to compensate for insulin resistance
How does the rate of insulin secretion contribute to GDM?
rate of insulin secretion (insulin secretion rate, ISR) is significantly lower in women with GDM than women without
Describe the study by Homko. What did it indicate?
Insulin Secretion Expmnt:
- set blood glucose at about 8.9 mmol/L (a hyperglycemic clamp)
- as blood glucose increased to the clamp level, so did the ISR
- when blood glucose was held constant, the ISR of women with GDM was lower than the controls
Insulin Resistance Expmnt:
- glucose infusion rate (GIR) was higher for controls than for GDM patients (indicating the glucose is not being taken up as fast)
