PMID- 37383391 OWN - NLM STAT- MEDLINE DCOM- 20230703 LR - 20230703 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension. PG - 1173402 LID - 10.3389/fendo.2023.1173402 [doi] LID - 1173402 AB - INTRODUCTION: Type II diabetes mellitus (T2DM) is a metabolic disorder that poses a serious health concern worldwide due to its rising prevalence. Hypertension (HT) is a frequent comorbidity of T2DM, with the co-occurrence of both conditions increasing the risk of diabetes-associated complications. Inflammation and oxidative stress (OS) have been identified as leading factors in the development and progression of both T2DM and HT. However, OS and inflammation processes associated with these two comorbidities are not fully understood. This study aimed to explore changes in the levels of plasma and urinary inflammatory and OS biomarkers, along with mitochondrial OS biomarkers connected to mitochondrial dysfunction (MitD). These markers may provide a more comprehensive perspective associated with disease progression from no diabetes, and prediabetes, to T2DM coexisting with HT in a cohort of patients attending a diabetes health clinic in Australia. METHODS: Three-hundred and eighty-four participants were divided into four groups according to disease status: 210 healthy controls, 55 prediabetic patients, 32 T2DM, and 87 patients with T2DM and HT (T2DM+HT). Kruskal-Wallis and chi2 tests were conducted between the four groups to detect significant differences for numerical and categorical variables, respectively. RESULTS AND DISCUSSION: For the transition from prediabetes to T2DM, interleukin-10 (IL-10), C-reactive protein (CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG), humanin (HN), and p66(Shc) were the most discriminatory biomarkers, generally displaying elevated levels of inflammation and OS in T2DM, in addition to disrupted mitochondrial function as revealed by p66(Shc) and HN. Disease progression from T2DM to T2DM+HT indicated lower levels of inflammation and OS as revealed through IL-10, interleukin-6 (IL-6), interleukin-1beta (IL-1beta), 8-OHdG and oxidized glutathione (GSSG) levels, most likely due to antihypertensive medication use in the T2DM +HT patient group. The results also indicated better mitochondrial function in this group as shown through higher HN and lower p66(Shc) levels, which can also be attributed to medication use. However, monocyte chemoattractant protein-1 (MCP-1) levels appeared to be independent of medication, providing an effective biomarker even in the presence of medication use. The results of this study suggest that a more comprehensive review of inflammation and OS biomarkers is more effective in discriminating between the stages of T2DM progression in the presence or absence of HT. Our results further indicate the usefulness of medication use, especially with respect to the known involvement of inflammation and OS in disease progression, highlighting specific biomarkers during disease progression and therefore allowing a more targeted individualized treatment plan. CI - Copyright (c) 2023 Yousef, Khandoker, Feng, Helf and Jelinek. FAU - Yousef, Hibba AU - Yousef H AD - Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates. FAU - Khandoker, Ahsan H AU - Khandoker AH AD - Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates. AD - Healthcare Engineering Innovation Center, Khalifa University, Abu Dhabi, United Arab Emirates. FAU - Feng, Samuel F AU - Feng SF AD - Department of Science and Engineering, Sorbonne University Abu Dhabi, Abu Dhabi, United Arab Emirates. FAU - Helf, Charlotte AU - Helf C AD - Dermatology, Venereology and Allergology, University Hospital Schleswig-Holstein, Schleswig-Holstein, Germany. FAU - Jelinek, Herbert F AU - Jelinek HF AD - Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates. AD - Healthcare Engineering Innovation Center, Khalifa University, Abu Dhabi, United Arab Emirates. AD - Biotechnology Center, Khalifa University, Abu Dhabi, United Arab Emirates. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230613 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 130068-27-8 (Interleukin-10) RN - 0 (Interleukin-6) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications MH - Interleukin-10 MH - *Prediabetic State/complications MH - Inflammation/complications MH - *Hypertension/complications MH - Interleukin-6 MH - Disease Progression PMC - PMC10296202 OTO - NOTNLM OT - hypertension OT - inflammation OT - mitochondrial dysfunction OT - oxidative stress OT - prediabetes OT - type II diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/06/29 13:42 MHDA- 2023/07/03 06:41 PMCR- 2023/01/01 CRDT- 2023/06/29 11:50 PHST- 2023/02/24 00:00 [received] PHST- 2023/05/26 00:00 [accepted] PHST- 2023/07/03 06:41 [medline] PHST- 2023/06/29 13:42 [pubmed] PHST- 2023/06/29 11:50 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1173402 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Jun 13;14:1173402. doi: 10.3389/fendo.2023.1173402. eCollection 2023.