Serum level of retinol binding protein 4 in obese individuals with insulin resistance and with 2 type diabetes mellitus treated by metformin

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Slide 1 :

Serum level of retinol binding protein 4 in obese individuals with insulin resistance and with 2 type diabetes mellitus treated by metformin M. Tajtáková 1, Z. Semanová 1, G. Ivancová 2, J. Petrovicová 3, V. Donicová 2, E. Žemberová 4 1 1st Department of Internal Medicine, Safarikiensis University 2 Internal Medical and Diabetological service 3 Department of Medical Information, Safarikiensis University 4 RIA laboratórium, Košice, Slovakia ____________________________________________________ 9th European Congress of Endocrinology,Budapest-Hungary 2007

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Introduction The relationship between obesity and insulin resistance (IR) and diabetes mellitus type 2 (DM2) has been studied with high attention in the last years. Especially, the effects of adipokines produced by fat tissue are of interest.

Slide 3 :

The effects of adipokines ? They have autocrine, paracrine and endocrine effects and can affect appetite, energetic metabolism, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism, homeostasis. ? Their production depends on the volume and distribution of fat tissue. ? They modulate effects of obesity to metabolism.

Slide 4 :

The increase of the visceral fat tissue results in (1) increased release and subsequent storage of free fat acids and decreased effect of insulin in insulin sensitive tissues (skeletal muscles and liver), which results in insulin resistance subsequent storage of free fat acids in ß cells of pancreas (resulting in apoptosis of the ß cells of pancreas).

Slide 5 :

The increase of the visceral fat tissue results in (2) dysregulation of the adipokines production, decrease of the production of the insulin sensitizing adipokines (adiponectin) and increase of the production of the inflammatory adipokines, which affect insulin resistance ( IL6, TNFa, resistin, angiotensin II, RBP 4).

Slide 6 :

Aim of the study ? To find out whether there is a difference between serum RBP4 levels in obese patients with insulin resistance without diabetes mellitus type 2 and non obese healthy individuals, and whether RBP4 correlates with insulin and adiponectin. ? To compare serum RBP4 level in obese individuals with insulin resistance without diabetes mellitus type 2 with serum RBP4 level in obese individuals with compensated DM2, who have been treated for more than 1 year with Metformin (500 - 800 mg/day, HbA1c = 7 %).

Slide 7 :

Group characteristics 56 individuals of similar age At the biginning, the 11 obese individuals with DM2 treated by Metformin were supposed to be a part of the same group as 39 obese individuals with IR or DM2 . However, the results concerning serum level of RBP4 in these two groups were different. Therefore, we created two subgroups of obese individuals.

Slide 8 :

Group characteristics 56 individuals of similar age males: 24 (average age 50,6 ± 10,2) females: 32 (average age 50,9 ± 10,1) SUBGROUPS ? 28 obese (BMI 34,3 ± 4,6) with insulin resistance (IR HOMA 3,9 ± 1,9) without diabetes mellitus type 2 (IR) ? 11 obese individuals (BMI 35,9 ± 6,1) with diabetes mellitus type 2 treated with Metformin or more than 1 year (DM2) ? 17 healthy nonobese individuals (BMI 24,3 ± 2,9) without insulin resistance ( IR HOMA 1,1 ± 0,4) (CON)

Slide 9 :

Analysis of examined parameters ? BMI ( weight in kg/height in m2) WHR (waist/hip ratio) ? Blood pressure was measured with a mercury manometer ? Glycemie and triacylglycerides were estimated by routine biochemical methods ? Insulin was estimated by RIA ? Insulin resistance indexes IR HOMA ( glucose Ohr.x insulin Ohr./ 22.5) ? Plasma concentrations of RBP4 were measured by radioimmunoassay

Slide 10 :

Statistical analysis All the data are expressed as means ± SE. One-way Analysis of Variance- ANOVA) or its non-parametric parallel in cases of differences between scatters or low number of values (Kruskal-Wallis one-way analysis) as wel as regression and correlation analysis were used.

Slide 11 :

Examined parameters

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Results In both groups (IR, CON) RBP4 correlated positively with insulin (r = 0,46 P= 0,03 ) and negatively with adiponectin (r = - 0,38 P= 0,05 ).

Slide 13 :

Results BMI (kg/m2) p< 0.001 NS p< 0.001 34,3?4,6 35,9?6 24,3? 2,9 RBP4 (ng/ml) p< 0.001 NS p< 0.05 561,6?209 391,9?133 452,8?104

Slide 14 :

Results The highest serum RBP4 levels in the group were noticed in obese individuals wíth insulin resistence. Despite the fact, that there was no statistical difference in BMI between individuals with IR and DM2, there was a significant difference found in serum RBP4 levels

Slide 15 :

Conclusion (1) ? The increased serum RBP4 levels by affecting the expression of GLUT4 transporter in adipocytes in obese individuals can play a role in the pathogenesis of insulin resistance and diabetes mellitus type 2 as an indirect factor, which affects insulin action predominantly in skeletal muscle. (The GLUT4 transporter is a protein which is important for the transmembranous transport of glucose)

Slide 16 :

Conclusion (1) ? The serum RBP4 level is increased in obese individuals with insulin resistance before manifestation of diabetes mellitus type 2. Therefore it could serve as: 1) a marker of worsened glucose tolerance in obese individuals, 2) an early indicator of the risk of development of diabetes mellitus type 2 in obese individuals with insulin resistance.

Slide 17 :

Insuline sensitisers ? Metformin as well as thiazolidinediones belong to insulin sensitisers, which improve insulin sensitivity ( Staes, 2006; Moo et al., 2007). ? Thiazolidinediones in experiment leads to increased levels of adiponectin (insulin sensitising adipokin) and to decrease of RBP4, which affects insulin resistance (Yang et al., 2006). ? Metformin does not affect serum adiponectin levels (Sharma et al., 2006; Kim et al.,2007).

Slide 18 :

Conclusion (2) Studies concerning the effects of metformin on RBP4 have not been published yet. ? Based on our results we assume that the effects of metformin involve also the adipose tissue, and metformin as an insulin sensitiser can improve insulin sensitivity by affecting the expression of RBP4 in adipocytes. However, this needs to be confirmed by a further research.

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