PCOS treatment Flashcards
What is the central metabolic defect associated with PCO?
-insulin resistance
how is insulin resistance in PCOS different to type 2 diabetes?
- type 2 diabetes insulin production eventually stops when cells dont respond.
- whereas in insulin resistance(pre-diabetes) in PCOS circulating insulin levels increase to compensate = hyper- insulinaemia
What is the role of insulin in maintaining glucose levels?
-when glucose levels are low, insulin is released by pancreatic cells (converts glycogen => glucose) allowing glucose to enter cells for energy.
What happens to glucose levels if you’re in insulin resistance state in PCOS?
- initially insulin levels increase converting glycogen => glucose so levels are maintained, but as you become more insulin resistant, you get glucose levels rising in the blood (hyperglycaemic) bc it cant enter the cells for energy and remains in the blood circulation.
What is the difference between PCO and PCOS?
PCO = polycystic ovary - variant in the normal ovary, not the disease
PCOS= polycystic ovarian syndrome - metabolic disorder associated with unbalanced hormones.
PCOS, IR, adiposity and androgen levels
- women with PCOS have central adiposity, which is linked to IR
- May NOT be due to higher relative percentage of visceral fat
- in animals exposure to androgen is associated with increased fat (women with PCOS have higher levels of androgen so put on weight easier)
Insulin sensitivity in relation to weight
- Everyone becomes less insulin resistant as they put on weight
-as you put on weight insulin sensitivity decreases even more in women with PCO than women with normal ovary.
-PCOS are more likely to put on weight so even more likely to be insulin resistant - high insulin due to IR is inherent in PCOS affecting 75-90% of women with PCOS.
-increased inflammatory substances come in as a result of obesity come and increase insulin resistance
Is insulin resistance caused by inherited insulin receptor gene mutation or by defect in the molecular mechanism pathway(familial)?
-IR is familial/inherited bc no mutation in the insulin receptor gene found in PCOS which cause less binding and resistance but it is a defect in the post- receptor binding somewhere in the signalling pathway
outline the basic mechanism of IR
1 insulin binds to insulin receptor on the cell membrane
2. phosphorylates receptor and initiates downstream signalling
3. This triggers the release of GLUT4 receptors contained int the vesicle which migrate to the cells surface allowing glucose to enter from blood stream into the cell.
=> defect somewhere along this pathway leads to insulin resistance so glucose cant enter cell and accumulates in blood stream (hyperglacemic)
How does obesity make it worse?
-macrophages/inflammatory markers (come in as a result of obesity) can cause IR.
OGTT - oral glucose tolerance test
- determine impaired tolerance
- Fasting 8-12hrs before test -> glucose given as a solution -> blood samples taken (0-2h) to determine how quickly cleared (insulin resistance cant clear it quickly, high levels persist)
What are normal values for fasting glucose and values after 2hrs in IGT?
- fasting value= <5.6 mM
- at 2h = 6-7.8mM
anything above shows impaired glucose tolerance:
1. impaired - fasting= 6-7
- at 2h =7.9-11mM
2. Diabetic
-Fasting value = >7 mM
-At 2hrs = > 11mM
Women with PCOS and prevalence of IR, T2D and GDM
- 30-40% women with PCOS have impaired glucose tolerance (IGT) and 10% develop TDM by age 40 y/o
-higher incidence of T2DM in women with family history i.e Indian sub continent Asians. - obesity exacerbates many aspects of PCOS clinical hormonal and metabolic features in women
Why does obesity and insulin resistance result in gestational diabetes (GDM) in pregnant women?
Placenta produces E, cortisol & human
placental lactogen(HPL)
↓
HPL interferes with insulin receptors
↓
Maternal Hyperglycemia
↓
Increased glucose in maternal
circulation crosses to foetal circulation
↓
Increase in fetal insulin
↓
Excess fetal growth – large for
gestational age
=> after pregnancy HPL decreases and goes back to normal
Complications if GDM for mothers
- birth weight (38%)
- shoulder dystocia/birth injury (22%)
- premature delivery (16%)
- Preclampsia (28%)
What are other manifestations of metabolic defect in PCOS?
tendency to obesity with increase in truncal-abdominal fat
* increased hypertension
* Altered lipid profile
– higher levels of LDL cholesterol – regardless of BMI
– low levels of HDL cholesterol and elevated triglycerides
* apparent increased risk for atherosclerotic disease
– Increased coronary artery calcification (independent of age & BMI)
– Increased carotid artery intima-media thickness (predictor of stroke & MI)
compared to age-matched controls
– Limited longitudinal studies → PCOS diagnosed during reproductive lifespan
(20-30 years old) but CVD manifests 30 to 40 years later.
– Also majority of conducted research on CVD on male →concept that women
present differently
* Recent study showed that women with PCOS at ↑risk of
osteosarcopenia (Kazemi M et al (2020) JCEM 105:e3400-e3414)
Why do women with PCOS gain weight?
Constant tendency to gain weight:
– Normal-weight women with PCO consistently maintain a lower-calorie diet than their counterparts with normal ovaries.
– HRQoL study in women with PCOS → normal-weight
women experienced as many problems with their
weight as obese women.
Why are women with PCOS more inclined to gaining weight?
PCOS is associated with reduced energy
expenditure equivalent to over 17,000 kcal/pa, compared to their normal counterparts who can burn these calories easily.