Disorders of uric acid metabolism as а manifestation of obesity phenotype in patients with type 2 diabetes (part 1)

Abstract

Uric acid (UA) metabolism disorders are known to be a common manifestation of insulin resistance syndrome in patients with type 2 diabetes, which is usually  associated with the general and/or abdominal obesity. 74 men with type 2 diabetes mellitus (Т 2DM) were divided into 5 groups according to the level of uric acid (UA)  in the blood serum (normourikemiya — NU, or hyperuricemia — HU), and to the presence of general and abdominal obesity (AO). Groups of patients with general  obesity, relatively high levels of insulin, a significant degree of insulin resistance, were added by us to the phenotype «obese T2DM» (or «alimentary-kinetic»). Patients  without obesity and significant increase in the level of insulin and HOMA IR, were marked by a other phenotype — «non-obese T2DM» The characteristic feature of  both phenotypes, regardless of body mass index and type of fat distribution, was overproduction of UA, which could be accompanied by a high clearance and  fractional excretion of UA (that provided NU), or by reduced excretion of UA, which led to HU. Phenotype «obese T2DM» in the presence of AO in the groups of patients  with similar levels of uricosuria was associated with higher insulin levels and the degree of IR and changes in lipid profile in comparison with relevant indicators in groups of patients with phenotype «non-obese T2DM». Only in men with hyperuricemia without obesity a significant decrease of the index of reutilization  of purines, which corresponds to the reduced activity of the enzyme hypoxantinguaninphosphoribosil trasnpherase (HGRT), which prevents the degradation of purines  with the formation of the UK was revealed. We concluded that advantageous mechanisms of disorders of purine and lipid metabolism in patients were  different depending on the phenotype. In obese patients, UA overproduction, hypertriglyceridemia and low HDL levels could be provoked by relatively high level of  insulin, which is known as a stimulant of lipogenesis to increase triglyceride, and has antiuricosuric effect. In non-obese patients, increased UA production can be  attributed to augmented desintegration of purines, which was not be related to increased insulinemia, but may be due to the activation of the catabolism of purines,  simultaneously with violation of their reutilization (due to the lack HGRT) that it is possible under the influence of stress hormones.