Pharmacogenetics of Sulfonylurea-Induced Hypoglycemia in Type 2 Diabetes Patients: the SUCLINGEN Study

Loganadan, Navin Kumar; Huri, Hasniza Zaman; Vethakkan, Shireene Ratna; Hussein, Zanariah

doi:10.2217/pgs-2021-0059

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Структурные варианты генов ABCC8 (rs757110), KCNJ11 (rs5219), CDKAL1 (rs7756992) и KCNQ1 (rs2237892) не были связаны с гипогликемией, индуцированной СМ (p > 0,05). Единственным предиктором их развития была предшествующая госпитализация по причине тяжелой гипогликемии (OR = 16,44; 95 % ДИ 1,74-154,33, p = 0,014) [19].…”

Section: Discussionunclassified

Relationship between the efficacy of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in patients with type 2 diabetes mellitus with different phenotypes

Bondar’,

Filipenko,

Shabel’nikova

et al. 2024

Sibirskij nauchnyj medicinskij zhurnal

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Recently, a large number of studies have been conducted to investigate the variability of response in the treatment of diabetes mellitus (T2DM), which make personalized medicine possible. However, the available data are insufficient to decide on the choice of sugar-lowering drugs in T2DM. The search for phenotypic and clinical factors of pharmacogenetic response to therapy continues. Aim of the study was to investigate the relationship between the effectiveness of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in T2DM patients with clinical phenotypes. Material and methods. A cross-sectional clinical and pharmacogenetic study of 1271 patients with T2DM receiving sulfonylurea monotherapy (SU) or in combination with metformin and divided into three clinical phenotypes: with insulin deficiency (insulinopenic phenotype), with obesity and moderate insulin resistance (classical phenotype) and with severe insulin resistance (insulin-resistant phenotype) was performed. A glycated hemoglobin content of less than 7% was considered as a good response to SU therapy. Results. Patients with a good response to SU therapy with a classic phenotype had a longer duration of diabetes compared to patients with absence of good response (5.68 ± 5.22 vs 9.12 ± 6.10 years, respectively, p < 0.001) and a later age at diagnosis of T2DM (54.05 ± 7.18 vs 49.37 ± 7.65 years, respectively, p < 0.001); patients with an insulin-resistant phenotype had T2DM established at an older age (54.35 ± 7.91 vs 50.10 ± 7.51 years, respectively, p = 0.001). Logistic regression analysis did not reveal a statistically significant association of the genotype of the structural variant of the ABCC8 gene (rs757110) with the effectiveness of SU in clinical phenotypes. The T/T genotype of the KCNJ11 gene (rs5219) was associated with a better response to SU therapy only in the group of T2DM patients with the classic phenotype (odds ratio 1.85, 95% confidence interval 1.05–3.25, p = 0.041). Conclusions. In patients with type 2 diabetes, predictors of a good response to SU with a classic phenotype were a later age of T2DM diagnosis, a shorter duration of diabetes, and the presence of the T/T genotype of the structural variant of the KCNJ11 gene (rs5219); with an insulin-resistant phenotype, a later age of T2DM diagnosis; with the insulinopenic phenotype no clinical and genetic predictors of the SU effectiveness were identified.

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Section: Discussionunclassified

Relationship between the efficacy of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in patients with type 2 diabetes mellitus with different phenotypes

Bondar’,

Filipenko,

Shabel’nikova

et al. 2024

Sibirskij nauchnyj medicinskij zhurnal

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“…Phase I clinical trial indicated berberine effectively reduced blood glucose levels without evoking hypoglycemia. [8] Nevertheless, traditional blockers of potassium K ATP channels, e. g. sulfonylurea, could induce hypoglycemia, [9] weight gain or other adverse effects [10] in patients with type 2 diabetes. Thus, promotion of stimulus-secretion coupling by closure of potassium channel is an oversimplified strategy to cure diabetes.…”

Section: Introduction 1ion Channels Regulate Metabolic Homeostasismentioning

confidence: 99%

Multidisciplinary Advances Address the Challenges in Developing Drugs against Transient Receptor Potential Channels to Treat Metabolic Disorders

Wang

2023

ChemMedChem

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Transient receptor potential (TRP) channels are cation channels that regulate key physiological and pathological processes in response to a broad range of stimuli. Moreover, they systemically regulate the release of hormones, metabolic homeostasis, and complications of diabetes, which positions them as promising therapeutic targets to combat metabolic disorders. Nevertheless, there are significant challenges in the design of TRP ligands with high potency and durability. Herein we summarize the four challenges as hydrophobicity, selectivity, mono‐target therapy, and interspecies discrepancy. We present 1134 TRP ligands with diversified modes of TRP‐ligand interaction and provide a detailed discussion of the latest strategies, especially cryogenic electron microscopy (cryo‐EM) and computational methods. We propose solutions to address the challenges with a critical analysis of advances in membrane partitioning, polypharmacology, biased agonism, and biochemical screening of transcriptional modulators. They are fueled by the breakthrough from cryo‐EM, chemoinformatics and bioinformatics. The discussion is aimed to shed new light on designing next‐generation drugs to treat obesity, diabetes and its complications, with optimal hydrophobicity, higher mode selectivity, multi‐targeting and consistent activities between human and rodents.

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Glyburide confers neuroprotection against age-related macular degeneration (AMD)

Picard,

Youale,

Hyman

et al. 2024

Translational Research

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Pharmacogenetics of Sulfonylurea-Induced Hypoglycemia in Type 2 Diabetes Patients: the SUCLINGEN Study

Cited by 3 publications

References 42 publications

Relationship between the efficacy of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in patients with type 2 diabetes mellitus with different phenotypes

Relationship between the efficacy of sulfonylurea therapy and structural variants of the ABCC8 (rs757110) and KCNJ11 (rs5219) genes in patients with type 2 diabetes mellitus with different phenotypes

Multidisciplinary Advances Address the Challenges in Developing Drugs against Transient Receptor Potential Channels to Treat Metabolic Disorders

Glyburide confers neuroprotection against age-related macular degeneration (AMD)

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