Haplotypes of the genes (GCK and G6PC2) underlying the glucose/glucose-6-phosphate cycle are associated with pancreatic beta cell glucose sensitivity in patients with newly diagnosed type 2 diabetes from the VNDS study (VNDS 11)

Zusi, Chiara; Rinaldi, Elisabetta; Bonetti, Sara; Boselli, Maria Linda; Trabetti, Elisabetta; Malerba, Giovanni; Bonora, Enzo; Bonadonna, Riccardo C.; Trombetta, Maddalena

doi:10.1007/s40618-020-01483-3

Cited by 4 publications

(5 citation statements)

References 57 publications

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“…Because of the small number of patients, lack of randomization, and insufficient reporting of secondary outcomes in published studies [ 30 ], several authors have performed meta-analyses. One meta-analysis of six studies (heterogeneity [ I 2 ]: 54%) and another of seven studies ( I 2 : 55%) published in December 2020 and January 2021, respectively, revealed no significant difference in the risk for the development of a fatal or severe course of illness with the use of DPP-4is in patients with COVID-19 [ 31 , 32 ]. Two subsequent meta-analyses with very low heterogeneity, published in February 2021 and March 2021 and included nine and ten studies, respectively, came to similar conclusions [ 33 , 34 ], with the exception of some benefits of in-hospital use of DPP-4is.…”

Section: Discussionmentioning

confidence: 99%

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study

et al. 2021

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Introduction To investigate the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM). Methods A multicenter, retrospective cohort study was conducted using patient data extracted from the Turkish National Electronic Database. All patients who tested positive for COVID-19 (PCR test) between 11 March through to 30 May 2020 were screened for eligibility ( n = 149,671). Following exclusion of patients based on pre-determined inclusion criteria, patients with T2DM using a DPP-4i or glucose-lowering medications other than a DPP-4i were compared for mortality and hospitalization. The propensity score method was used to match age, gender, micro- and macrovascular complications, and medications in the two groups. Independent associates of mortality were analyzed using multivariable analysis on the whole T2DM population. Results A total of 33,478 patients with T2DM who tested postive for COVID-19 who met the inclusion criteria were included in the analysis. Median (interquartile range) age was 54 (22) years and 42.4% were male. Of these, 9100 patients using DPP-4is ( n = 4550) or other glucose-lowering drugs ( n = 4550) were matched in two groups. After matching, analysis revealed a lower mortality in the DPP-4i group (9.5 vs. 11.8%; p < 0.001). In the multivariable model, the use of DPP-4is (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35–0.91; p = 0.02) was associated with lower mortality in the whole sample, while age, male gender, computed tomography finding of COVID-19, obesity, low glomerular filtration rate, and an insulin-based regimen also predicted increased risk of death. There was no association between the preexisting treatment with DPP-4is and COVID-19-related hospitalization in the matched analysis or multivariate model. The rate of admission to the intensive care unit and/or mechanical ventilation favored the DPP-4i group (21.7 vs. 25.2%; p = 0.001), although this association became saturated in the multivariate analysis (OR 0.65, 95% CI 0.39–1.08; p = 0.099). Conclusions The results of this study demonstrate an association between DDP-4i use and reduced mortality in people with T2DM who tested PCR positive for COVID-19.

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Section: Discussionmentioning

confidence: 99%

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study

et al. 2021

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“…HMGC and CYP7A1 are key enzymes in cholesterol synthesis. PLIN1 not only regulates the process of lipolysis but also promotes the formation of lipid droplets . ELOVL6 is involved in fatty acid elongation and acyl-CoA biosynthesis .…”

Section: Discussionmentioning

confidence: 99%

“…PLIN1 not only regulates the process of lipolysis but also promotes the formation of lipid droplets. 37 ELOVL6 is involved in fatty acid elongation and acyl-CoA biosynthesis. 38 In this study, fluoride reduced the expression of IRS2 and G6PC while elevated the expression of MYC, SREBF1, GCK, FASN, HMGCR, CYP7A1, PLIN1, ELOVL6, and SCD2.…”

Section: ■ Discussionmentioning

confidence: 99%

Multiomics Analysis Revealed the Molecular Mechanism of miRNAs in Fluoride-Induced Hepatic Glucose and Lipid Metabolism Disorders

Zhao

Ommati

et al. 2022

J. Agric. Food Chem.

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Fluoride-induced liver injury seriously endangers human and animal health and animal food safety, but the underlying mechanism remains unclear. This study aims to explore the mechanism of miRNAs in fluoride-induced hepatic glycolipid metabolism disorders. C57 male mice were used to establish the fluorosis model ( 22.62 mg/L F − , 12 weeks). The results indicated that fluoride increased fluoride levels, impaired the structure and function, and disrupted the glycolipid metabolism in the liver. Furthermore, the sequencing results showed that fluoride exposure resulted in the differential expression of 35 miRNAs and 480 mRNAs, of which 23 miRNAs were related to glycolipid metabolism. miRNA−mRNA network analyses and RT-PCR revealed that miRNAs mediated fluoride-induced disturbances in the hepatic glycolipid metabolism. Its possible mechanism was to regulate the insulin pathway, PPAR pathway, and FOXO pathway, which in turn affected the bile secretion, the metabolic processes of glucose, the decomposition of lipids, and the synthesis of unsaturated fatty acids in the liver. This study provides a theoretical basis for miRNAs as diagnostic indicators and target drugs for the treatment of fluoride-induced liver injury.

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“…SNP selection was performed as previously reported 29,30 . Briefly, three genomic areas based on the International HapMap Project Phase III data on the CEU population were screened: (a) ADIPOQ gene, plus 10 kb on its 3′ flanking region and 3 kb on the 5′, on chromosome 3q27.3; (b) human chromosome 7q32.1 encompassing the LEP gene; (c) LEPR gene, as well as 3 kb of its 3′ flanking region, within 1p31.3 chromosome.…”

Section: Methodsmentioning

confidence: 99%

“…SNP selection was performed as previously reported. 29,30 Briefly, three genomic areas based on the International HapMap Project Phase III data on the CEU population were screened: (a) ADIPOQ gene, plus 10 kb on its 3 0 flanking region and 3 kb on the 5 0 , on chromosome 3q27.3; (b) human chromosome 7q32.1 encompassing the LEP gene; (c) LEPR gene, as well as 3 kb of its 3 0 flanking region, within 1p31.3 chromosome. Based on Tagger analysis using GEVALT (GEnotype Visualization and ALgorithmic Tool) software, five SNPs (rs182052, rs822396, rs12495941, rs1501299, rs2241767) within the ADIPOQ gene, three SNPs (rs4731426, rs10244329, rs11761556) on the LEP region and seven SNPs within the LEPR gene (rs7602, rs7537093, rs1475397, rs1171267, rs11208680, rs10749754, rs6678033) were selected as tagging SNPs covering at least 95% of the common genetic variability.…”

Section: Genotypingmentioning

confidence: 99%

Crosstalk between genetic variability of adiponectin and leptin, glucose‐insulin system and subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study 14

Zusi,

Csermely,

Rinaldi

et al. 2023

Diabetes Obesity Metabolism

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Aim To evaluate the relationship of genetic variability of adiponectin (ADIPOQ), leptin (LEP) and leptin receptor (LEPR) genes with glucose‐insulin system and markers of subclinical atherosclerosis (ATS) in patients with newly diagnosed type 2 diabetes. Materials and methods In 794 subjects we performed: 1) euglycemic hyperinsulinemic clamp to assess insulin sensitivity; 2) mathematical modelling of a 5h‐OGTT to estimate β‐cell function; 3) resting ECG; 4) carotid artery and lower limb artery eco‐doppler sonography to identify ATS; 5) genotyping of tag‐SNPs within ADIPOQ, LEP and LEPR gene. Results Regression analyses showed: 1) adiponectin levels were negatively associated with BMI, waist‐to‐hip ratio and triglycerides and positively with HDL and insulin sensitivity (p‐all<0.03); 2) leptin levels were positively associated with BMI, HDL‐cholesterol and plasma triglycerides and negatively with insulin sensitivity (p‐all<0.001). Two SNPs (rs1501299 and rs2241767) within ADIPOQ gene were associated with circulating levels of adiponectin. The ADIPOQ‐GAACA haplotype was associated with plasma adiponectin (p=0.034; β=‐0.24), ECG abnormalities (p=0.012; OR=2.76), carotid ATS (p=0.025; OR=2.00) and peripheral limb artery ATS (p=0.032; OR=1.90). The LEP‐CTA haplotype showed an association with ischemic ECG abnormalities (p=0.017; OR=2.24). Finally, LEPR‐GAACGG was associated with circulating leptin (p=0.005; β=‐0.31) and worst β‐cell function (p=0.023; β=‐15.10). Omnibus haplotype analysis showed that ADIPOQ haplotypes were associated with levels of adiponectin and common carotid artery ATS, LEP with peripheral limb artery ATS, whereas LEPR haplotypes influenced circulating levels of leptin. Conclusions Results of this study reinforce knowledge on adipokines’ role in regulating glucose metabolism; in particular highlighted the potential atherogenic role of leptin and the anti atherogenic role of adiponectin.

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Haplotypes of the genes (GCK and G6PC2) underlying the glucose/glucose-6-phosphate cycle are associated with pancreatic beta cell glucose sensitivity in patients with newly diagnosed type 2 diabetes from the VNDS study (VNDS 11)

Cited by 4 publications

References 57 publications

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study

Multiomics Analysis Revealed the Molecular Mechanism of miRNAs in Fluoride-Induced Hepatic Glucose and Lipid Metabolism Disorders

Crosstalk between genetic variability of adiponectin and leptin, glucose‐insulin system and subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study 14

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