Transporters, TBC1D4, and ARID5B Variants to Explain Glycated Hemoglobin Variability in Patients with Type 2 Diabetes

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Vanessa Gonzalez-Covarrubias ◽  
Héctor Sánchez-Ibarra ◽  
Karla Lozano-Gonzalez ◽  
Sergio Villicaña ◽  
Tomas Texis ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Glucose Control ◽  
Plasma Levels ◽  
Prediction Models ◽  
Glycated Hemoglobin ◽  
Clinical Chemistry ◽  
Diabetic Patients ◽  
Genetic Associations ◽  
Hemoglobin Variability

<b><i>Introduction:</i></b> Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin. <b><i>Methods:</i></b> HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach. <b><i>Results:</i></b> We identified genetic variants on <i>SLC47A1, SLC28A1, ABCG2, TBC1D4,</i> and <i>ARID5B</i> that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on <i>SLC47A1</i>, <i>SLC28A1</i>, and <i>ABCG2</i> likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis. <b><i>Conclusions:</i></b> Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.

scholarly journals Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1283 ◽  
Author(s):  
AlKhairi ◽  
Cherian ◽  
Abu-Farha ◽  
Madhoun ◽  
Nizam ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Positive Association ◽  
Diabetic Patients ◽  
Metabolic Dysregulation ◽  
Strong Positive Association ◽  
Metabolic Biomarkers ◽  
Diabetes And Obesity

Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients (p < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals (p < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and p = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay.

scholarly journals The role of glycated hemoglobin (HbA1c) and serum lipid profile measurements to detect cardiovascular diseases in type 2 diabetic patients

2016 ◽  
Vol 5 (2) ◽  
pp. 30-34 ◽  
Author(s):  
Muhammad Naeem ◽  
Rehman Mehmood Khattak ◽  
Mati Ur Rehman ◽  
Muhammad Nasir Khan Khattak
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Lipid Profile ◽  
Serum Lipid ◽  
Glycated Hemoglobin ◽  
Density Lipoprotein ◽  
Serum Lipid Profile ◽  
Diabetic Patients

Patients with diabetes are considered to be at more risk of dyslipidemia and hypertension, hence targets for cardiovascular diseases. This study describes the possible role of Glycated Hemoglobin (HbA1c) and serum lipid profile as a biomarker in the detection of cardiovascular diseases. A cross-sectional study was carried out on 54 (33 males and 21 females) type 2 diabetes (T2DM) patients at Ayub Teaching Hospital (ATH), Abbottabad and Mardan Medical Complex (MMC), Mardan, Khyber Pukhtunkhwa (KP), Pakistan. The control group comprised of 20 (13 males and 7 females) healthy human samples. The patients had significantly higher (p<0.05) Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), HbA1c, Fasting Blood Glucose (FBG), Total Cholesterol (TC), Triglyceride (TG) compared to control subjects. Only High Density Lipoprotein (HDL) was found to be significantly (p<0.05) lower in the patients compared to controls. With regards to gender, in the female patients SBP, DBP, TC and Low Density Lipoprotein (LDL) were significantly higher (p<0.05) compared to males patients. The HbA1c was found to be significantly higher (p<0.05) in males. Results also revealed that patients having HbA1c>7.0%, had higher TG than those with HbA1c?7.0%. Furthermore, 14.2% patients with HbA1c>7.0% had cerebrovascular diseases and 28% have ischemic heart diseases. The findings of the current study suggests association of HbA1c with lipid profile in T2DM patients and both might be used as a predictor of cardiovascular diseases in such patients.South East Asia Journal of Public Health Vol.5(2) 2015: 30-34

scholarly journals Plasma Resolvin D2 to Leukotriene B4 Ratio Is Reduced in Diabetic Patients with Ischemic Stroke and Related to Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhijuan Miao ◽  
Xin Tang ◽  
Marianne Schultzberg ◽  
Yuwu Zhao ◽  
Xiuzhe Wang
Keyword(s):  
Ischemic Stroke ◽  
Plasma Levels ◽  
Leukotriene B4 ◽  
Good Prognosis ◽  
Diabetic Patients ◽  
Stroke Severity ◽  
Proinflammatory Mediators ◽  
Prognosis Group ◽  
Good Prognosis Group

Background. Diabetes mellitus (DM) aggravates symptoms and prognosis of acute ischemic stroke (AIS), and inflammation plays an important role therein. Resolvin D2 (RvD2) is one of the specialized pro-resolving mediators (SPMs), while leukotriene B4 (LTB4) is a classic proinflammatory mediator. The ratio of RvD2 to LTB4 is an index of pro-resolving/proinflammatory balance. We aim to explore the role of RvD2/LTB4 ratio in ischemic stroke complicated with DM. Methods. The plasma levels of RvD2 and LTB4 were analyzed by enzyme immunoassay in stroke patients with DM (DM + AIS group) or without DM (nonDM+AIS group). Patients were followed up at 90 days after stroke onset, and modified Rankin Score (mRS) was assessed. The association of RvD2/LTB4 ratio with stroke severity and prognosis was also analyzed. Results. The plasma levels of RvD2 were positively correlated to LTB4. The RvD2/LTB4 ratio in DM + AIS group was lower than that in the nonDM+AIS group. No correlation was found between the RvD2/LTB4 ratio and infarct size or NIHSS score. The RvD2/LTB4 ratio at baseline was significantly lower in the poor prognosis group ( mRS ≥ 3 ) than that in the good prognosis group ( mRS ≤ 2 ). Conclusions. Our study indicated that the balance between pro-resolving and proinflammatory mediators was impaired by diabetes in ischemic stroke. The RvD2/LTB4 ratio may serve as a biomarker of prognosis for ischemic stroke.

Associations with metabolites in Chinese suggest new metabolic roles in Alzheimer’s and Parkinson’s diseases

2019 ◽  
Author(s):  
Jin-Fang Chai ◽  
Suryaprakash Raichur ◽  
Ing Wei Khor ◽  
Federico Torta ◽  
Wee Siong Chew ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Metabolic Pathways ◽  
Genetic Associations ◽  
Complex Disorders ◽  
Genome Wide ◽  
Parkinson’S Diseases ◽  
Metabolite Concentrations ◽  
Sphingosine 1 Phosphate ◽  
Novel Associations

Abstract Metabolites are small intermediate products of cellular metabolism perturbed in a variety of complex disorders. Identifying genetic markers associated with metabolite concentrations could delineate disease-related metabolic pathways in humans. We tested genetic variants for associations with 136 metabolites in 1,954 Chinese from Singapore. At a conservative genome-wide threshold (3.7 x 10-10), we detected 1,899 variant-metabolite associations at 16 genetic loci. Three loci (ABCA7, A4GALT, GSTM2) represented novel associations with metabolites, with the strongest association observed between ABCA7 and d18:1/24:1 dihexosylceramide. Among 13 replicated loci, we identified six new variants independent of previously reported metabolite or lipid signals. We observed variant-metabolite associations at two loci (ABCA7, CHCHD2) that have been linked to neurodegenerative diseases. At SGPP1 and SPTLC3 loci, genetic variants showed preferential selectivity for sphingolipids with d16 (rather than d18) sphingosine backbone, including sphingosine-1-phosphate (S1P). Our results provide new genetic associations for metabolites and highlight the role of metabolites as intermediate modulators in disease metabolic pathways.

Genetic variants associated with glycemic response to treatment with dipeptidylpeptidase 4 inhibitors

2020 ◽  
Vol 21 (5) ◽  
pp. 317-323 ◽  
Author(s):  
Anna Űrgeová ◽  
Martin Javorský ◽  
Lucia Klimčáková ◽  
Jozef Židzik ◽  
Ján Šalagovič ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Glycated Hemoglobin ◽  
Missense Variant ◽  
Response To Treatment ◽  
Diabetic Patients ◽  
Glycemic Response ◽  
European Origin ◽  
Central European ◽  
Dipeptidylpeptidase 4

Aim: We examined associations of eight SNPs in/near seven candidate genes with glycemic response to 6 month treatment with DPP4 inhibitors. Patients & methods: 206 patients with type 2 diabetes (116 men and 90 women) were treated with sitagliptin or vildagliptin (both 100 mg/day) in combination with metformin or metformin/sulphonylurea over 6 months, and the reduction in glycated hemoglobin (HbA1c) was measured. Results: Rs6923761 in GLP1R was significantly associated with a reduction in HbA1c (adjusted p = 0.006). Homozygotes for the minor A allele had smaller reduction in HbA1c by 0.4% (4 mmol/mol) than the G allele carriers (p = 0.016). Conclusion: The missense variant rs6923761 in the  GLP1R gene was associated with a smaller glycemic response to 6 month gliptin therapy in diabetic patients of central European origin.

scholarly journals Role of Glycated Hemoglobin on Islets Cell Autoantibody Mediated Insulin Resistance in Type 2 Diabetic Patients

2020 ◽  
Vol 8 (10) ◽  
pp. 2355-2360
Author(s):  
Dr. Saimun Nahar Rumana ◽  
Dr. Mohammad Moniruzzaman ◽  
Dr. Arif Mahmud Jewel ◽  
Dr. Qumruzzaman .
Keyword(s):  
Insulin Resistance ◽  
Glycated Hemoglobin ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Thyroid hormone-catecholamine interrelationships during exposure to cold

1981 ◽  
Vol 97 (1) ◽  
pp. 91-97 ◽  
Author(s):  
H. Storm ◽  
C. van Hardeveld ◽  
A. A. H. Kassenaar
Keyword(s):  
Nervous System ◽  
Plasma Concentration ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Plasma Levels ◽  
Surgical Procedure ◽  
Exposure To Cold ◽  
Basal Plasma ◽  
Sympathetic Nervous

Abstract. Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation. The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level. During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.

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