Meta-Inflammation in Type 2 Diabetes Mellitus: Theoretical, Methodological, and Clinical Aspects.

Currently, there is no doubt that insulin resistance (IR) in prediabetes and type 2 diabetes mellitus (T2DM) is associated with chronic systemic metabolic inflammation (SMI). SMI is typically considered a form of low-grade systemic inflammation (LGSI). At the same time, one cannot rule out the possibility of the transformation of LGSI into more pronounced forms of chronic systemic inflammation (ChSI), typical of systemic autoimmune diseases and characterized by a high severity of systemic inflammatory response (SIR). The aim of this research is to assess the pathogenetic role of SMI as a general pathological process in the pathogenesis of prediabetes and T2DM, as well as differentiating SMI into LGSI and ChSI. The study included two main groups-T2DM (<i>n</i> = 65) and prediabetes (<i>n</i> = 24)-as well as three control groups of healthy individuals of different ages (<i>n</i> = 50, <i>n</i> = 89, and <i>n</i> = 22). In the patients of the main groups, metabolic syndrome (MetS) was diagnosed in accordance with the American Heart Association criteria, and metabolic indices (HOMA-IR, HOMA-islet, and TyG) were calculated. The levels of C-reactive protein (CRP) and cytokines (TNFα, IL-6, IL-8, and IL-10) were determined in blood plasma as SIR parameters, and the levels of cortisol (690 nmol/L or <100 nmol/L), D-dimer (>250 and >500 ng/mL), and troponin I (>0.2 ng/mL) were used as additional SMI criteria. Based on molecular inflammatory markers, the ChSI and LGSI scales were calculated using the authors' original method. SMI in T2DM and prediabetes manifested itself as both LGSI (in 57% of cases in T2DM and 46% in prediabetes) and ChSI (in 18.5% of cases in T2DM and 8.3% in prediabetes). The verification of SMI based on the frequently used criterion of CRP levels above 3 mg/L turned out to be ineffective in our study (this criterion was detected in the control groups in 24-45%). Therefore, we used CRP > 10 mg/L in combination with cytokines as the SIR criterion. Additionally, we identified the SMI criteria: D-dimer > 250 ng/mL in 27.7% of T2DM and 0% in the control groups and prediabetes; cortisol 15.4% in T2DM and 8.3% in prediabetes; and troponin I 7.7% in T2DM and 4.2% in prediabetes. SMI (LGSI and ChSI) develops in the majority of patients with prediabetes (54.1%) and T2DM (75.4%). To assess SMI, it is advisable to use the integral SIR criteria in combination with the markers of chronic stress, tissue damage, and coagulopathy.