what is 40 : 1 in management of dr. jyoti agarwal dr. sharda jain dr. jyoti bhaskar
TRANSCRIPT
What is
40 : 1 In management of
Dr. Jyoti Agarwal Dr. Sharda Jain Dr. Jyoti Bhaskar
Not end of the storyToday knowledge regarding PCOS
has revived and efforts have been undertaken to explore new options
created significant development in t/t of
PCOD
Insulin resistance is a primary
ROOT cause in PCOS
Indian Journal of Endocrinology and Metabolism, 2011
Central player : IR
Insulin Resistance
A pathophysiological contributor in
50 – 80 % of the PCOS women
Indian J Endocrinol Metab. 2011 Oct-Dec; 15(4): 239–241.
75% of PCOS patients are obese
• Relative risk of MI is 7.4 times higher wrt age matched controls.
• risk of diabetes associated death.
• PCO is present in 42 % of CVD patients.
J.Clin.Endocrinol.Metab., December 2013
PCOS and metabolic syndrome
The use of insulin lowering or insulin sensitizing therapy may help to improve ovarian function and menstrual cyclicity.
Word “M ”in the PCOS world
First being - Metformin
Miracle pill - Myoinositol
MYO-INOSITOL and METFORMIN
Myo-inositol
Improves insulin
sensitivity Decreases insulin
resistance levels
Improves glucose
utilization
Restores menstruation and normal ovulation
Reduces free testosterone
Improves pregnancy
rate
MYO-INOSITOL - takes TOTAL CARE OF SYMPTOMS
Insulin acts like a key which can open the
door on the cell surface
1 •Insulin binds to its receptor forms a complex called insulin receptor substrate (IRS).
2 •IRS stimulates messenger called PI 3 kinase
3 •Activated PI 3 kinase activates GLU T 4
4 •Glucose is then taken by GLUT 4 through glucose channel for utilizing energy.
5 •Then IRS complex breaks down releasing the receptor to go back to its original site.
Glucose metabolism in a normal cell
Phosphatidyl inositol 3-kinase is the key messenger
• We need production & activation of PI 3 kinase
for normal cell glucose metabolism.
• Inositol produces as well as activates PI3 kinase
Inositol acts as a precursor for PI 3 kinase
Fertility and Sterility Volume 86, Issue 3, Supplement 1, September 2006, S461 J Pediatr Endocrinol Metab 2000;13 Suppl 5:1295-8
What is the connection between PCOS and
inositols ???
In PCOS there is deficiency of
inositolDIABETES CARE 2006, 29, 300-305
Inositol levels in PCOS and Normal women
PCOS Subjects Normal Subjects 0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
0.18
0.2
0.1
0.190000000000001
p=0.035
PCOS Subjects Normal Subjects 0
0.5
1
1.5
2
2.5 2.3
0.700000000000001
p= 0.043
Diabetes Care 2006;29:300–305
Plasma inositol (µmol/l) 24 h urinary inositol ((µmol/l/day)
Normal Plasma inositol (µmol/l) levels – 0.13-0.28
PCOS Subjects Normal Subjects 02468
10121416
15.3
2.7
p= 0.001
Inositol clearance levels in PCOS and Normal women
Diabetes Care 29:300–305, 2006
Urin
ary
clea
ranc
e of
Inos
itol
(ml/
min
)
5 -6 times more Urinary
clearance of Inositol in PCOS
Could inositols be considered
to treat PCOD ???
Myoinositol is not a drug• It is naturally occuring
one of the nine isomer of a C6 sugar alcohol that belongs to the vitamin B complex group (B 7 )
• Synthesised in the liver from glucose in our body
• Water soluble so each dose is well tolerated and is devoid of toxicity
It is commonly found in fruits (grapefruit being a rich source), vegetables (leafy vegetables the
lowest) and in all foods containing seeds (beans, almonds and walnuts the
highest).
Enzyme Epimerase converts Myo inositol to D chiro Inositol
Conversion is insulin dependent
When insulin resistance occurs, the conversion rate is affected
Excess insulin in the ovary triggers Epimerasation
In overweight PCOS BMI > 25 • The insulin resistance is
very high.• Epimerase activity is
triggered.• Disturbs the
physiological 40 : 1 plasma ratio of Myo-inositol : D Chiro Inositol.
Insulin regulates blood glucose by two ways
1) Promoting glucose cell
uptake
2) Glycogen synthesis
Eur.Rev.Med.Pharmacol.Sci., 2013
Insulin action needs “second messengers”
MYO promotes glucose cell intake
DCI stimulates glycogen
synthesis.
DCI is present in high concentrations in glycogen storage tissue (liver, muscles and fat)
low in tissue needing elevated energy levels (brain, ovary, heart).
Myo – inositol• Acts at ovary
• Increases glucose cell intake
• Normalises LH :FSH ratio
• Increases oocytes quality
• Reduces the amount of FSH used during IVF cycles
• Improves IVF results
DCI• Acts at peripheral tissues
• Stimulates glycogen synthesis
• Reduces IR• Increases insulin sensitivity• Reduces hyperinsulinemia
• No effect at ovarian level• No direct effect on fertility
• Reduces risk of metabolic syndrome
• 19 out of 22 obese pts ovulated (1.2 mgm/day)
• These results were not confirmed in second clinical trial when double dose of DCI was given.
• Negative effect of DCI at ovaryNestler et al 1999
The DCI “paradox” in the ovary
In overwt. PCOS
High Insulin levels increases conversion of MI to DCI in the ovary
Ovary unlike other tissues never shows insulin resistance
The DCI “paradox” in the ovary
• In the ovary, MYO is involved in FSH signalling, while
• DCI is responsible for insulin-mediated testosterone production.
Endocrine J., 2014
Net result is that in the ovary
• Increase DCI• Promotes androgen
synthesis
• MI depletion• Worsens the energy
state of the occyctes
These events together impair FSH signalling and oocyte
quality
Treat PCOS the right way !!
MI/DCI physiological plasma ratio
40:10
10
20
30
40
50
Study 1 Study 2 Study 1+2
Clinical Evidences forMYO-INOSITOL and D –
chiro inositol combination
50 overwt. PCOS
Treatment results seen at 3 & 6 mnths
Significant improvement in plasma glucose,insulin concentration at 3 months
Improvement in total testosterone and SHBG was seen at both 3 and 6 months
20 overwt. PCOS
With combination therapy a significant improvement was seen in
• Lipid profile• BMI• Waist : Hip ratio• Blood pressure• Homa index
Thus……
Combined treatment in physiological ratio of 40 : 1 is able to restore both hormonal and metabolic
parameters in overweight PCOS women earlier than with MI alone
And hence the Rationale of
40 : 1MI : DCI
Safety of inositol combination
Remarkably, in all the studies analyzed, no side effects have been reported.
No drug interactions documented yet
• Start the treatment as soon as the diagnosis of PCOD is made
• Dose is 2 grams of MYO and 50 mg of DCI twice a day (powder).
• If taken as powder , presence of caffiene decreases its absorption
Caffeine-induced MYO malabsorption
Carry Home Message PCOD treatment
is a challenge.
Treatment should address the root cause.
Best therapy should include a 360° approach to the problem, taking into consideration the complexity of the syndrome.
Combined therapy may be the first line approach in
overweight PCOS
European Review for Medical and Pharmacological Sciences
ADDRESS 11 Gagan Vihar, Near Karkari
Morh Flyover, Delhi - 51
CONTACT US 9650588339, 011-22414049,
WEBSITE : www.lifecarecentre.in
www.drshardajain.com www.lifecareivf.com
E-MAIL [email protected]
[email protected]@lifecareivf.com
&
Thank You