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INTERNAL MEDICINE
Assessment of Insulin Resistance and Effect of Metformin
in Non Alcoholic in Steatohepatosis
Mithlesh Kumar

Introduction: Insulin resistance plays a major role in the pathogenesis of non alcoholic steatohepatitis (NASH). Insulin-
sensitizing drugs like metformin may have a role in treatment in this disease.
Objective: To determine insulin resistance and role of metformin in the treatment of NASH.
Material and Methods: We prospectively studied 25 patients with NASH over a period of one and half years. In addition to
clinical pathological profile, we studied the insulin resistance by insulin tolerance test in 10 of them; seven of them, who did
not respond to 3 months of low-calorie, low-fat diet, exercise, weight reduction with metformin for six month. Results were
compared with control groups.
Results: All 10 patients with NASH tested had low insulin sensitivity; there was significant difference in the rate constant for
insulin sensitivity (kit) between patients with NASH and normal volunteers. Thirteen (52%) patients responded to dietary
restriction, exercise, weight reduction and UDCA. Four of 7 patients treated with metformin had normalization of ALT.
Conclusion: Patients with NASH have insulin resistance. Metformin may have a role in treatment of these patients.
JIAMSE IAMSE 2009 Volume 19 2S 68
INTERNAL MEDICINE
Association of Polymorphisms in Interleukin-4 and
Interleukin-10 Genes with Graves’ Disease in Iranian
Patients
Omid Khalilzadeh1, Mehdi Anvari2, Alireza Esteghamati3, Aliakbar
Amirzargar3
1Molecular Immunology and Immunogenetics Research Center 2Endocrinology and Metabolism Research Center (EMRC)
Introduction: Graves’ disease (GD) is the most common form of autoimmune thyroid disease with a still largely unclear
etiology. Among genetic factors that may contribute to the development and progression of the disease and its complications
are polymorphisms in the genes encoding cytokines. In the present study, we focused on gene polymorphisms of two important
cytokines, namely interleukin-4 (IL-4) and IL-10.
Material and Methods: Venous sample of participants were obtained and DNA was extracted by salting out method. Using
PCR-restriction fragment length polymorphism method (PCR-RFLP), the association between GD and the following
polymorphisms was studied in 107 patients and 140 healthy controls: IL-4 (-1098T/G, -590T/C, -33C/T), and IL-10 (-
1082A/G, -819C/T, -592A/C).
Results: For IL-4, the -1098G allele, TG genotype and GG genotype increased the odds of having the disease 3.08- (P <
0.0001), 2.56- (P = 0.0041) and 105-fold (P < 0.0001), respectively. The -590T allele and TC genotype decreased the odds of
having the disease 2.13- (P < 0.0001) and 12.5-fold (P < 0.0001), respectively. The -33T allele and TT genotype increased the
odds of having the disease 2.52-fold (P < 0.0001) and 118.83 (P < 0.0001), respectively. For IL-10, the -1082G allele and GG
genotype increased the odds of having the disease 2.16- (P < 0.0001) and 2.05-fold (P = 0.0246), respectively. The -819T
allele, TC genotype and TT genotype increased the odds of having the disease 2.16- (P < 0.0001), 2.09- (P = 0.0114) and 4.58-
fold (P = 0.0003), respectively. The -592C allele and CC genotype decreased the odds of having the disease 2.44- (P < 0.0001)
and 5.56-fold (P < 0.0001), respectively.
Conclusion: This study showed the significant association of polymorphisms in IL4 and IL10 with graves disease. Future
studies are needed to confirm our findings.
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JIAMSE IAMSE 2009 Volume 19 2S 69
INTERNAL MEDICINE
The Validation of IGF-I and P-III-P Assays in the
Development of a Methodology to Detect Growth Hormone
Abuse in Sport
A.J. Skingle

Introduction: It is believed Growth hormone (GH) and Insulin-like growth factor-I (IGF-I) are abused by athletes for their
anabolic and lipolytic properties. There is currently no test to detect doping with IGF-I and the test for GH abuse can only
detect individuals who have taken GH in the last 36 hours.
The GH-2000 team developed formulae based on serum IGF-I and P-III-P levels that can determine if an individual is taking
GH in up to 90% of cases. These formulae were developed using the Nichols IGF-I assay and the CIS P-III-P immunoassay,
unfortunately the Nichols assay is no longer available. The relationship of other IGF-I assays to each other and to Nichols is
vital in being able to apply these formulae to values achieved from the currently available IGF-I assays. The CIS P-III-P assay
measures in different units to the other commercially available P-III-P assay Orion, this in itself is not a problem and is akin to
measuring weight in stones or kilograms but it is important to know the relationship between them.
Material and Methods: One hundred and twenty four serum samples were assayed for IGF-I with two commercially available
immunoassay kits (DSL and Immunotech) and for P-III-P with two further radioimmunoassays (CIS and Orion). The body
composition of eleven amateur athletes was estimated using air displacement plesthymography (BODPOD), bioimpedance and
skinfold thickness. Physical fitness was estimated by a maximal treadmill test following the Bruce Protocol.
Results: Serum IGF-I to P-III-P showed a positive correlation of r = 0.388 and p≤0.01.Serum IGF-I to body fat percentage by
all estimates showed no significant relationship with all r<0.1 and all p values over 0.7. I found the DSL to immunotech
conversion factor to be Immunotech = 0.7828 X [DSL] and CIS to Orion conversion to be Orion = 9.2057 X [CIS] giving
similar results to previous work done in this area. This work allows values achieved from current IGF-I and P-III-P assays to
be converted into values that can be used in the GH-2000 formulae to detect GH abuse.
Conclusion: The development of conversion factors for the commercially available immunoassays takes us one step closer to a
reliable test for rhGH abuse.
JIAMSE IAMSE 2009 Volume 19 2S 70
INTERNAL MEDICINE
The Correlation Between LH to FSH Ratio and Metabolic
Factors in Indonesian PCOS Patients; Preliminary Study
I. Kusumaningtyas, S.N. Yuwono
Faculty of Medicine University of Indonesia
Introduction: Polycystic ovarian syndrome (PCOS) is common endocrine disorder affecting female fertility, including in
Indonesia. Metabolic factors are related with the clinical manifestation of PCOS (i.e. insulin, glucose levels, Body Mass
Index). From the previous study, LH to FSH ratio has been used as a value that correlate with degree of severity in patient with
PCOS. Other factor that may contribute to clinical sign is area under curve of Insulin (AUC-I). This research is proposed to
see which factor mentioned above that might has stronger correlation with LH to FSH ratio in PCOS patient in Indonesia.
Material and Methods: The data were collected in Cipto Mangunkusumo General Hospital and Hermina Maternal and Child
Hospital from January till November 2008. These patients were physically examined and followed by serum LH, FSH, Fasting
glucose, fasting insulin and 2 hours postprandial insulin measurement. AUC-I was calculated by using positive incremental
formula.
Results: The strong correlation between LH to FSH ratio and fasting insulin was observed in this study (r: 0.663, P<0.05). In
addition, we also observed strong correlation between LH to FSH ratio and AUC-I (r: 0.639, P<0.05). During this study we did
not find any correlation between LH to FSH ratio and fasting glucose level (r: 0.342, P>0.05); LH to FSH ratio and BMI (r:
0.323, P>0.05); and LH to FSH ratio and 2 hours postprandial insulin (r: 0.228, P>0.05).
Conclusion: The result of our study shows that the increasing of LH to FSH ratio shows a strong correlation with the fasting
insulin and AUC-I. The increasing of insulin has an independent correlation with glucose level, BMI and 2 hours postprandial
insulin. This result is similar with the previous study that shows increasing insulin had a stronger correlation with abdominal
obesity than BMI. Glucose levels have no correlation with the increasing LH to FSH ratio because most of the PCOS patients
have a normal glucose levels. The increasing of LH to FSH ratio has a strong correlation with AUC-I but not with 2 hours
postprandial insulin. It is suggested the result measurement of 2 hours postprandial insulin shows a wide variation. The
conclusion of our study is that fasting insulin and AUC-I has a strong correlation with increasing LH to FSH ratio, independent
to glucose levels, BMI and 2 hours postprandial insulin.
JIAMSE IAMSE 2009 Volume 19 2S 71

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