Metformin in PCO---How it helps-the cellular dynamics of metformin? Should we prescribe to all PCO women or be selective??

Why PCO is harmful for blood vessels?? Why & how it causes hypertension?

PCO is compared with Viper venom?? Why? Nowadays  it is clear that PCOS  is a pro inflammatory state    and  emerging   data suggest that chronic low grade   inflammation   supports  the development of  metabolic aberration and ovarian dysfunction .CRP is the most    reliable    circulating marker of chronic low grade   inflammation in PCOS  . Recently    CRP   was found to be a direct promoter of the   atherosclerotic   processes and  endothelial cell  inflammation   leading to  athero thrombosis . CRP has a  direct   role in the vascular  inflammatory   process  stimulating  the release   of inflammatory   cytokines  and increasing   endothelial  expression of cellular  adhesion   molecule  which mediate    leukocyte  migration . Findings of a study  suggest that increased  cardiovascular   risk may be seen in 83.3 % of the PCO women with CRP >  2.42  mg /1 .CRP  values < 1  mg / 1 are  considered low  risk  1-3   mg/ 1 are considered  intermediate  risk and  3-10   mg / 1    are considered high   risk for cardiovascular   disease .  Why PCO is compared with Viper venom?? Nowadays  it is clear that PCOS  is a pro inflammatory state    and  emerging   data suggest that chronic low grade   inflammation   supports  the development of  metabolic aberration and ovarian dysfunction .CRP is the most    reliable    circulating marker of chronic low grade   inflammation in PCOS  . Recently    CRP   was found to be a direct promoter of the   atherosclerotic   processes and  endothelial cell  inflammation   leading to  athero thrombosis . CRP has a  direct   role in the vascular  inflammatory   process  stimulating  the release   of inflammatory   cytokines  and increasing   endothelial  expression of cellular  adhesion   molecule  which mediate    leukocyte  migration . Findings of a study  suggest that increased  cardiovascular   risk may be seen in 83.3 % of the PCO women with CRP >  2.42  mg /1 .CRP  values < 1  mg / 1 are  considered low  risk  1-3   mg/ 1 are considered  intermediate  risk and  3-10   mg / 1    are considered high   risk for cardiovascular   disease . 

  There have been debates about which method will be clinically superior to establish the diagnosis of insulin resistance?? HOMA index though very accurate is not a very comfortable  method  and it is  also expensive  and time consuming for this   reason the need for a simple way of measuring   insulin resistance   has led to the creation  of a large  number   of insulin sensitivity  indices.  The most    used model is the HOMA  index.

  

Q.1. Then , what is the best acceptable method of assessing  Insulin resistance in day to day clinical practice ?? Anms:  A) OGTT is most acceptable method till date which is useful in day to day practice. Other available methods are cumbersome and not feasible for clinical use though may be of help in research settings.  OGTT, is still  the most accurate    method to diagnose insulin   resistance. One has to ingest  75  g glucose challenge even   in adolescent  women. Normal values are the following a) Normoglycemia: fasting 70-100  mg/ dL

60 min after   glucose administration < 180  mg / dL

120 min after glucose administration < 140 mg/ dL

 b) Impaired  glucose   tolerance is defined  when glucose level is > 140  mg/ dL 2 hour  after glucose load   but < 200 mg /dL  .

  c) Diabetes   is defined   when glycemia  is > 200 mg/ dL   2 h after   glucose  load

 Q. 2: What is the normal insulin level in healthy women & men??  Ans:-What do we mean by normo insulinaemiac?? Ans:- normoinsulinemia : implies when a)  Fasting  insulin is  < 10 mUI /mL b) 60 min after glucose administration  < 60 mUI/mL c) 120 min after  glucose   administration , =  10 mUI/mL .Of course   the majority  of PCOS   patients   are not diabetic yet but only insulin resistant .

 Q.3:-How to define then insulin resitance based on serum insulin level?? Ans:-Insulin resistance is defined when insulin value   one h after OGTT is > 60 mUI/ mL  and / or   its level   is not very   close   to the fasting   insulin  value   after 2 h   post glucose administration.

Q. 4:  In a diagnosed case of PCO how often one should perform PPBS then ?? It has  been suggested  that an OGTT    be performed   every   2 years   for those  with normal   glucose tolerance and annually if IFG  or IGT    is present . Glucose screening recommendation for PCOS  women are  summarized  .

 Q.5: What about HOMA index??  Ans- The homeostatic model for assessment   of insulin resistance    is a simple and noninvasive   method of estimating    insulin   sensitivity from the steady glucose   and insulin concentrations measured under fasting  conditions  .

Examining scientific literature studies  are very conflicting  to each other   and a  unanimous opinion  on the effectiveness of insulin   sensitizing  drugs  has not yet been  reached.

According  to the ASRM committee  of 2008   insulin   sensitizing  agents   should  be considered in patients    with impaired   glucose  tolerance   and PCOS.

In 2010  AE- PCOS  Society   consensus  treatment   emphasized that   metformin  should be  used in women with PCOS   who have  already   started  lifestyle    treatment      and do not   have improvement in IGT   or in those  who have normal   weight  but still having  .

When   administered to insulin resistant patients these drugs    act to increase  target  tissue  responsiveness in order  to reduce   hyperinsulinemia .

In the past   limited   studies    on the use of Diazoxide acarbose and somatostatin  for PCOS women    were conducted  then thiazolidinediones aroused  more interest   while to  date metformin is the most   worldwide studied insulin  sensitizing agent . Moreover   statins  have also been used to improve   lipid profile  in PCOS women .