Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity
Open accessAbstract
Diabetes mellitus is a metabolic disease that causes a hyperglycemic status which leads, over time, to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The most frequent form of diabetes is type 2 diabetes mellitus (T2DM) which is often part of a metabolic syndrome (hyperglycaemia, hypertension, hypercholesterolemia, abdominal obesity) that usually requires the use of several medications from different drug classes to bring each of these conditions under control. T2DM is associated with an increase in inflammatory markers such as interleukin-6 (IL-6) and the tumor necrosis factor alpha (TNF-α). Higher levels of IL-6 and TNF-α are associated with a downregulation of several drug metabolizing enzymes, especially the cytochrome P450 (P450) isoforms CYP3As and CYP2C19. A decrease in these P450 isoenzymes may lead to unexpected rise in plasma levels of substrates of these enzymes. It could also give rise to a mismatch between the genotypes determined for these enzymes, the predicted phenotypes based on these genotypes and the phenotypes observed clinically. This phenomenon is described as phenoconversion. Phenoconversion typically results from either a disease (such as T2DM) or concomitant administration of medications inducing or inhibiting (including competitive or non-competitive inhibition) a P450 isoenzyme used by other substrates for their elimination. Phenoconversion could have a significant impact on drug effects and genotypic-focused clinical outcomes. As the aging population is exposed to polypharmacy along with inflammatory comorbidities, consideration of phenoconversion related to drug metabolizing enzymes is of importance when applying pharmacogenomic results and establishing personalized and more precise drug regimens.
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In T2DM patients, IL-6 and TNF-α levels are strikingly increased, and this is associated with downregulation of several drug metabolizing enzymes, leading to poor drug effects.
“In T2DM patients, IL-6 and TNF-α levels are strikingly increased. This is also associated with a downregulation of several drug metabolizing enzymes, which leads to poor drug effects [11].”
From The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2021) · cites this paper as [11]
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Self-citationDel Toro-Pagán, N. M., Matos, A., Bardolia, C., Michaud, V., Turgeon, J., & Amin, N. S. (2022) · Figshare · doi:10.6084/m9.figshare.18849372
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Enhancing dental implant outcomes in type 2 diabetes: Addressing inflammation and risk factors
Xiao, L.-F., Xing, Y.-X., & Sun, N. (2026) · World Journal of Diabetes · doi:10.4239/wjd.v17.i2.113906
Bi, Z.-H., Liu, S.-C., Weng, Y.-H., Chen, J.-Y., Li, S. X., Lin, X.-Q., Liu, Y., & Miao, L. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1875319
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- Authors
- Darakjian, L., Deodhar, M., Turgeon, J., & Michaud, V.
- Affiliations
- Tabula Rasa HealthCare (United States) (US)
- Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-05-07
- Volume
- 22
- Issue
- 9
- Pages
- 4967
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC8124164
- OpenAlex
- W3158869533
- Cited by
- 53
- References
- 155
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 7 · 2023: 12 · 2022: 13 · 2021: 7
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- type 2 diabetes, chronic inflammation, cytochrome P450, CYP3A4/5, CYP2C19, phenoconversion, drug-metabolizing enzymes, interleukin-6, TNF-α, metabolic syndrome, polypharmacy, pharmacogenomics, drug interactions
- MeSH terms
- Animals, Chronic Disease, Cytochrome P-450 Enzyme System, Diabetes Mellitus, Type 2, Humans, Inflammation, Insulin, Models, Biological
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