JOURNAL READINGNUR AMIRA 112013037

DR HARIANTO SpOG

RELATIONSHIP BETWEEN INSULIN RESISTANCE AND HIGH MOLECULAR WEIGHT ADIPONECTIN IN NORMAL WEIGHT ADOLESCENT WITH POLYCYSTIC OVARY SYNDROME (PCOS) AND A MATERNAL HISTORY OF PCOS

TITLE

OBJECTIVE

• To assess rate of insulin resistance• Relationship between insulin resistance and high

molecular weight adiponectin in normal weight adolescent with polycystic ovary syndrome (PCOS) and a maternal history of PCOS

PCOS

• Endocrine disorder of women reproductive age • Menstrual disorder starts in peripubertal period

(oligomenorrhea, dysfunctional uterine bleeding)• Hyperandrogenism (hirsutism, acne, oily skin,

androgenic alopecia)• Infertility• Patient with PCOS has risk of insulin resistancy ,

hyperinsulinemia, obesity, and cardiovascular diseases

2 of 3 criteria• Oligo-ovulation /anovulation• Clinical or /and biochemical signs of hyperandrogenism• Polycystics ovaries by utrasound and exclusion of other

androgen excess disorder

ADIPONECTIN

• Adipocytokine (adipocyte derivative biologically active molecue generated from adipose tissue)

• Effective in the circulation as an • insulin sensitizer• anti inflammatory, and• anti atherosclerotic agent.

• Classified by three groups :• low, • medium , • high molecular weight adiponectin.

MATERIALS AND METHOD

PLACE• Adolescent clinic of Etlik Zubeyda Hasim Women’s

Health Teaching and Research Hospital, Ankara Turkey• April 2011- November 2011

• Oligomenorrhea –without menstrual bleeding frequency longer than 35 days

• Amenorrhea –without menstrual bleeding longer than 6 months

• Clinical hyperandrogenism – hirsutis, acne, oily skin, an androgenic alopecia

Inclusion criteria• PCOS diagnosed according to 2004 Rotterdem criteria• Age 15-20 years• BMI 18-25 kg/m2• Maternal History of PCOS

Control Group• Age and BMI matched adolescent with no family history

or diagnosis of PCOS or other reason and diseases.

Antropometric measurement • Subject wearing light clothing, without shoes.• Height and weight measured• BMI calculated in kg

Scoring of hirsutism (using modified Ferman Gallway System)• Score>8 =hirsutism

Alopecia (using Ludwig scoring)

Acne ( criteria Hayashi et all)

ALOPECIA AND ACNE SCORING

LUDWIG SCORING HAYASHI ET ALL

PCOS 4 phenotypes• 1: hyperandrogenism + OA ( anovulation) +PCOS• 2: hyperandrogenism + OA• 3: hyperandrogenism + PCOS • 4: OA + PCOS

• Blood samples –obtained in the morning after an overnight fast on day 3 of initiated or spontaneous menstrual cycle.

• Measured – free triodothronine, free thyroxin (FT4), TSH, DHEAS, PRL, FSH, LH, E2, 17a-hydroxyproestrone (17-OHP), free T, total T, total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL) cholesterol, and HMW adiponectin.

HORMONAL IMMUNOASSAYS

• Glucose + lipid profile measurement: using vitros chemistry system

• Serum FSH, LH, E2, PRL, P, total T, free T levels : chemiluminescence method

• DHEAS and 17-OHP levels were determined with the radioimmunoassay method

• HMW adiponectin –Buhlmann multimeric Adiponectin ELISA kit.

• Insulin- DiaMetra ELISA kit with micro ELISA method

STATISTICAL ANALYSIS

• Performed using statistical for social sciences.• Distribution of continuous variables checked using

Kolmogrov Smirnov Test

RESULTS

• Demographic charecteristics- presented in table 1• 1 excluded because lost to follow up.• Groups were comparable regarding BMI and age.• The clinical sign of hyperandrogenism were significantly

higher in PCOS group than in control group.

• 2nd hour glucose concentration in OGTT higher in the PCOS group.

• HMW adiponectin lower in PCOS group.• The insulin resistance was determined in 69% and 2.5 %

of adolescent in the PCOS and control group respectively.

• Insulin resistant PCOS adolescent level of HMW adiponectin was lower

• The adolescent + PCOS + biochemical hyperandrogenism lower HMW adiponectin

• The adolescent + PCOS + biochemical hyperandrogenism higher HOMA-IR compared with The adolescent + PCOS + biochemical normoandrogenism

• Normal weight , healthy adolescent with PCOS and maternal history of PCOS higher insulin resistance, lower HMW adiponectin than controls.

MAIN FINDINGS:-• IR can be found in normal weight adolescent with PCOS

(without metabolic disorder and obesity)• HMW adiponectin levels were negatively correlated with

IR.• Hyperandrogenism is associated with IR and low HMW

adiponectin in adolescent with PCOS.

• First degree relatives of women with PCOS have high risk of developing PCOS symptoms and endocrine disorders (obesity, IR, hyperlipidemia)

• Cross sex: 9 peripubertal girls + first degree relatives PCOS reduced by threefold compared to 10 age matched controls :insulin sensitivity

• Cross sex: 19 adolescent + mothers or sisters diagnosed with PCOS demonstrated lower insulin sensitivity compared to 21 healthy age matched controls.

• The women with PCOS have an 11 fold increase in the prevalence of metabolic syndrome, and the risk enhanced at young age.

• Women with PCOS have an increased of impaired glucose tolerance, type 2 diabetes, and metabolic syndrome compared with controls.

• Women with PCOS have a higher risk for early onset of cardiovascular diseases.

Villa et all• Demonstrated that in adolescent with PCOS, the basal

insulin value and HOMA-IR higher than in non PCOS group.

• Impaired glucose tolerance is an indicator for increased IR in nonobese adolescent with PCOS.

• Therefore, screening of IR should be considered for adolescent with PCOS independent of BMI

O’connor et al.• Total, medium and low molecular weight adiponectin

concentrations did not differ between the PCOS group and control.

• HMW adiponectin concentrations were significantly lower in the PCOS group.

• Conclusion, adolescent with PCOS had a significantly increased rate of IR independent of BMI.

• The HMW adiponectin levels were lower in normal weight + adolescent + PCOS and inversely correlated with IR.

• The IR with low HMW adiponectin levels may indicate the future development of metabolic disorders in adolescent with PCOS, even in the absence obesity.