Monday, 20 April 2020

Metabolic syndrome


These  findings strongly suggest a contribution of abnormal  metabolism of inositol to the insulin resistance in PCOS patient   which leads to a reduction in circulating   inositol and its availability  to the  tissues . Finally in conclusion  a defect in  tissue availability of inositol in PCOS contributes  to the  insulin resistance     leading to decreased  cellular  availability of the PI 3 kinase  mediated  insulin action.
Theory 3: Altered   insulin signaling and its relationship with IR and PCOS. 
PI 3  kinase is a mediator for glucose metabolism and  its utilization by the cell.
Deficiency of inositol alters  activity of PI3  kinase.
Reduced activity of PI 3 kinase  reduces  translocation of GLUT 4 thereby causing  hyperglycemia 
This brings about  altered  insulin  signaling causing  hyperinsulinemia   and   thus IR . Insulin resistance   thus is  responsible for PCOS. 
Pathway of inositol  deficiency and PCOS 
Metformin fails to manage Insulin Resistance in PCOS women
Metformin  is the most  commonly prescribed insulin   sensitizing drug  in the treatment   of PCOS. It  enhances insulin sensitivity   by activating PI 3   kinase  but it has been postulated  that Metformin has  a very restrictive mechanism of action due to which  it is not  a right  treatment   option for PCOS. How useful is metformin??Authentic journal statements  on the use of  metformin in PCOS 
In the absence of large  adequately powered placebo controlled trials  it is   difficult   to provide useful answers   about the longer  term   benefits  of metformin in PCOS women. However   there are more   side effects  with metformin  like lactic acidosis and malabsorption  including  poor adsorption of vitamin B12
Thus there arises a therapy which  cares  for each and every symptom of PCOS along with documented  safety. 
Now coming back to efficacy of MI:-How important is MI??  Myo- inositol – The Ultimate  Insulin Sensitizer
Myo- inositol a six  carbon sugar alcohol present abundantly in the body. The chemical name of myo inositol is 1,2, 3,,5/4,6- Hexahydroxycyclohexane   . It is a precursor of various cell membrane phospholipids.
Generally myo inositol  is present  in the cells. Serum  concentrations are   high during fetal life and later on falls However  during certain conditions like  polycystic  ovary   syndrome  physiological requirements  of myo inositol increased.
Myo inositol is an insulin  sensitizing agent produced by the human body from glucose  and is one of 9 distinct   isomers of  the nutrient inositol naturally produced by the human   body. It is  a vitamin  B  complex derived product that has been evaluated  in a number of controlled  studies  looking at ovulation frequency , time   to ovulation   follicular maturation and the quality of  oocyte    production  cell morphogenesis  and   cytogenesis   lipid synthesis the structure of cell membranes  and cell  growth . Myo   inositol plays  an important  role as the structural basis for a  number of  secondary messengers  like to synthesise phosphatidylinositol 3 kinase   a key messenger   to improve  insulin sensitivity   and glucose  utilization along with reduction of insulin  resistance.
PCO & Myoinositol:--Growing  evidences  of Myo inositol in PCOS
Studies have   found that  deficiency of inositol which is  precursor for phosphatidylinositol  3 kinase contributes to the  insulin resistance  in pcos   women. The women   with PCOS  are characterized by abnormal   metabolism of inositol and have  diminished insulin stimulates  releases of the putative phsophatidylinositol mediator.
Myo inositol significantly improves  insulin activity and  reduces   glucose level  in PCOS  patient. It also reduces  total testosterone as a result it   improves  hormonal   balance and ovulation. Elevated  concentration of myo inositol  in human   follicular    fluid  appears to play  important   role in follicular   maturity  and provides  good quality  oocytes.
Myo  inositol besides  improving hormonal profile and restoring  ovulation  is also  able to induce regular  menses in PCOS patients  . Finally  in conclusion myo inositol   increases  implantation  and pregnancy rate in PCOS  patients.
Clinical  effects of myo inositol  supplementation can be  summarized as follows :
Reduces  insulin  resistance   and increases   insulin sensitivity
Increases  glucose  uptake
Lowers insulin  levels 
Lower total and  free testosterone
Improves  menstrual  cycle  frequency
Improves  pregnancy  rate  and live birth rate
Lowers  triglycerides  and improves  lipid  profile .
As per ped Health 2010; Adolescent girls  with PCOS require a long  term committed treatment   . Therefore     alternative treatments may be possible  option for a subset of PCOS  adolescent females. Myo  inositol a component  of the vitamin B complex  has been shown  to improve  insulin signaling   thereby  restoring  normal   ovulatory   function  in PCOS  women.
Thus as Myo inositol takes care of the major  symptoms  associated with PCOS    Care  in established PCOS  cases and in adolescent  PCOS  cases .
Clinical  studies of Myo  inositol in PCOS
Myo inositol shows  56% reduction in HOMA  Index
P.G, Artini et al evaluated the   effects  the administration of myo  inositol  on hormonal  paratemeters  in a group of polycystic ovary  syndrome   patients  in a controlled clinical  study 50  overweight PCOS  patients   were enrolled after  informed   consent. All patients   underwent  hormonal   evaluations and  an oral glucose tolerance test  before and after 12  weeks of therapy    MYO 2 g plus folic  acid 200 mg every  day Group B  folic acid   200 mg Ultrasound examination  and Ferriman – Gallway score   were  also performed
Main outcome measures  were  plasma  LH, FSH, PRL , E2  17 OHP , A, T , glucose    insulin , c peptide concentrations , BMI, HOMA index  and glucose  to insulin  ratio.
 First of all in the MYO treated group  the duration    of stimulation  was lower  than  in control group   and also  r-FSH  units  used were fewer  in the MYO   treated group. The HOMA  index got  significantly reduced from 2.5 + 0.6 to 1.1 + 0.3   in the MYO group .However     in the control group  the HOMA  index  remained unchanged from 2.5 + 0.4  to 2.4 + 0.7
The   insulin levels  got significantly  reduced from  11.4 + 2.2  to 5.5 + 1.1  in the MYO  group However  in the control  group  the insulin   levels decreased  from 11.4  + 1.3  to 10+ 1.1

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