Consequences of insulin resistance, PCOS, ovarian and pregnancy Flashcards
What does maternal insulin resistance during pregnancy cause?
Maternal insulin resistance and obesity leads to foetal MACROSOMIA and large for gestational size. Larger babies more likely to injure themselves during birth. Increased risk of morbidity such as 3rd degree tear, obstructed labour, Caesarian section.
What is macrosomia defined as?
Generally greater than 4 kg ( absolute) or centile birthweight (90%
What are the main predictors of macrosomia?
GDM, DM and BMI
What can normal pregnancy be defined as?
A profoundly insulin resistant state (as measured by euglycaemic hyperinsulinaemic state). this can precipitate insulin secretion deficits.
What does maternal hyperglycaemia lead to?
Higher foetal omental fat
What are the mechanisms behind gestational DM?
adipocytokines, fatty acid metabolic and hormonal effects
What is the most important pregnancy hormone?
Human placental lactogen (v. important high secretion – but poorly understood seems to be imp in driving insulin resistance in mothers which allows calories to be given to the fetus)
What other hormones are affected? and another factor
In gestational diabetes, you get low adiponectin, not low Leptin and certain fatty acids. Beta cell failure
What do fatty acids do in pregnancy?
Free fatty acids increase insulin resistance in pregnancy: glucose tolerant women underwent euglycemic hyperinsulinemic clamp and received either lipid and heparin or saline infusions. Rates of total glucose disposal and carb and FO oxidation was measured. This showed that elevating FFA during pregnancy inhibits total body glucose uptake and oxidation. Elvated plasma FFA can contribute to peripheral insulin resistance seen in late pregnancy
What suggests beta cell failure?
The increased pro-insulin to insulin ratio, which predicts GDM
What happens to insulin secretion in GDM?
1996) In ladies with GDM they have lost their 1st phase insulin secretion but make more 2nd phase – but the failed 1st phase is what is crutial. After 3 hours they may have normal glucoe levels but they still had higher levels of glucose to start with
Why is the baby initially hyperinsulinaemic?
PEDERSON: glucose easily crosses the placenta but then can only get into adipocytes in the presence of insulin. The hyper glycaemia stimulates the fetal pancreas causing hyperinsulinaemia. After birth the baby keeps making insulin at the same rate leading to hyperglycaemia and feeding through a also gastric tube for a couple days.
How do triglycerides fit into GDM?
Triglyceride is a good predictor of macrosomia but it is not used clinically (does not cross placenta but can when hydrolysed to NEFAs). Amino acids can easily cross the placenta. Babies can grow not only by inc glucose but due to increase AA and TG/NEFA in the maternal circulation. Amino acid concs are inc when there is less insulin so in diabetes you get high gluc and high AA. AA are potent insulin secretogoes just like glucose. NEFA need to be broken down by placental lipase to become FA to pass through theplacenta and in excess can contribute to the fuel uptake
For fetal macrosomia is it just hyperglycaemia that matters?
HAPO study: associations with maternal BMI (controlled for confounders) looked at highest BMI and lowest. saw that obese mothers have higher birthweight babies, higher % fat in baby, inc risk of C section – so its not just sugar its obesity as well that matters.
What happens to the fat ratio of GDM mothers
Women with GDM were shown to have a lower polyunsaturated:saturated fat ratio
What is given for GDM?
Metformin is used in the treatment as it is just as effective often (some patients needed insulin) and reduced the risk of hypos (i.e. safer). The women on metformin also tended to have better weight lost post partum and the ladies prefered the treatment
What happens to the thermogenesis of GDM
Lean body mass is positively proportional to resting energy expenditure, GDM have reduced post prandial thermogenesis. Women before and after GDM have reduced insulin sensitive and PPT
22% of the extra energy required for pregnancy
This may form the benefit of the predisposition to NIDDM as it helps conserve energy