Assessment of Insulin Resistance and Effect of Metformin in Non Alcoholic in Steatohepatosis

Mithlesh Kumar

Kharkov National Medical University, Kharkov, Ukraine

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.

Association of Polymorphisms in Interleukin-4 and Interleukin-10 Genes with Graves’ Disease in Iranian Patients

Omid Khalilzadeh, Mehdi Anvari, Alireza Esteghamati, Aliakbar Amirzargar

Tehran University of Medical Sciences, Tehran Iran

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.

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

University of Southampton, Southhamptom, United Kingdom

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<0Conclusion: The development of conversion factors for the commercially available immunoassays takes us one step closer to a reliable test for rhGH abuse.

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, Jakarta, 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<00.05); 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.