Keywords
How to Cite
Abstract
Background and aims. Adiponectin is a hormone of adipose tissue, which is involved in the regulation of fatty acids catabolism, insulin sensitivity, blood glucose level, and other processes. Its serum level is significantly decreased in visceral obesity and pathological conditions that are associated with insulin resistance (IR). The aim of our study was to evaluate changes in serum adiponectin level, its diagnostic accuracy, and association with non-alcoholic fatty liver
disease (NAFLD) in patients with type 2 diabetes (T2D) depending on transaminases levels. Materials and methods. We have followed up 91 patients with
T2D, who were diagnosed for fatty liver by abdominal ultrasonography. All patients were divided into 3 groups. The control group (n=28) included patients with T2D without NAFLD. In the other two groups we identified patients with NAFLD and normal (n=37) or elevated (n=26) transaminases. To assess the diagnostic accuracy of adiponectin in NAFLD, ROC-analysis was used. Multiple logistic regression was used to identify factors independently associated with NAFLD.
Results. Serum adiponectin levels were significantly lower in the group with T2D and NAFLD with increased transaminases than in patients with normal transaminases and control group (2.74±1.43 vs 3.81±1.79 vs 6.2±2.04 μg/ml, p=0.001). In the univariate logistic regression adiponectin showed a protective effect against NAFLD development (OR = 0.451, 95%CI 0.317-0.641, p<0.001). According to stepwise multiple logistic regression, hypoadiponectinemia was associated with NAFLD independently on HOMA-IR (R2=0.528) and ALT (R2=0.563). To identify NAFLD in T2D patients, adiponectin proved to be a very effective diagnostic model, AUROC being equal to 0.871 (95%CI 0.795-0.946, p<0.001). The optimal cutoff value is set at <4.6 μg/ml with sensitivity, specificity, PPV and NPV equal to 79.4%, 82.1%, 90.9%, and 63.9%, respectively. To distinguish patients with NAFLD and elevated transaminases from patients with normal values, AUROC for adiponectin was 0,670 (95%CI 0.534-0.807, p=0.022). Adiponektin optimal cutoff value under which an increase in transaminases was reported in NAFLD patients <3.1mg/ml, with a sensitivity, specificity, PPV, and NPV equal to 61.5%, 59.5%, 51.6%, and 68.6%, respectively. Conclusion. Our study has demonstrated that hypoadiponectinemia - independently on IR and transaminases - was associated with NAFLD. Patients with elevated transaminases have a significantly lower serum adiponectin level. A decrease in adiponectin below 4.6 mg/ml can be used as a diagnostic marker of NAFLD in T2D patients.
References
2. Кравчун Н.А., Земляницина О.В., Тяжелова О.В. Неалкогольная жировая болезнь печени и сахарный диабет 2-го типа: клиника, диагностика, терапия // Ліки України. 2012, №3–4, 18-21.
3. Михальчук Л.М., Єфімов А.С. Неалкогольна жирова хвороба печінки // Міжнародний ендокринологічний журнал. 2010, № 2 (26), 71-82.
4. Scherer P.E., Williams S., Fogliano M. et al. A novel serum protein similar to C1q, produced exclusively in adipocytes // J. Biol. Chem. 1995, 270, 26746-26749.
5. Pajvani U.B., Du X., Combs T.P. et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/ adiponectin. Implications fpr metabolic regulation and bioactivity // J. Biol. Chem. 2003, 278, N11, 9073-9085.
6. Бабак О.Я., Колеснікова О.В., Шуть І.В. Вплив сироваткового рівня адипонектину на вираженість неалкогольного стеатозу печінки у хворих на цукровий діабет 2 типу з надлишковою масою тіла // Сучасна гастроентерологія. 2011, № 1 (57), 9-11.
7. Adachi M., Brenner D.A. High molecular weight adiponectin inhibits proliferation of hepatic stellate cells via activation of adenosine monophosphate-activated protein kinase // Hepatology. 2008, 47, 677-685.
8. Pajvani U.B. et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedionemediated improvement in insulin sensitivity // J. Biol. Chem. 2004, 279, 12152-12162.
9. Kubota N., Yano W., Kubota T. et al. Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake // Cell Metab. 2007, 6, N.1, 55-68.
10. Ebinuma H., Miida T., Yamauchi T. et al. Improved ELISA for selective measurement of adiponectin multimers and identification of adiponectin in human cerebrospinal fluid // Clin. Chem. 2007, 53, N8, 1541-1544.
11. Hara K., Boutin P., Mori Y. et al. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population // Diabetes. 2002, 51, 536-540.
12. Vasseur F., Helbecque N., Dina C. et al. Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocytesecreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians // Hum. Mol. Genet. 2002, 11, 2607-2614.
13. Gu H.F., Abulaiti A., Ostenson C.G. et al. Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetesin Swedish Caucasians // Diabetes. 2004, 53, 31-35.
14. Kubota N., Terauchi Y., Yamauchi T. et al. Disruption adiponectin causes insulin resistance neointimal formation // J. Bio.l Chem. 2002, 277, 25863-25866.
15. Maeda N., Shimomura I., Kishida K. et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 // Nat. Med. 2002, 8, 731-737.