scholarly journals Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes

2021 ◽  
Vol 8 ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Manjula Nandakumar ◽  
Ahmed Al-Qaissi ◽  
Thozhukat Sathyapalan ◽  
Stephen L. Atkin ◽  
...  

Background and Purpose: Patients with type 2 diabetes (T2D) have increased risk of cardiovascular disease (CVD), encompassing myocardial infarction, stroke, and peripheral vascular disease. We hypothesized that those biomarkers indicative of acute ischemic stroke (AIS) seen in large vessel occlusion (LVO) may also be elevated in T2D and further enhanced by stress conditions; therefore, these proteins represent potentially predictive biomarkers for those T2D patients at high risk of AIS.Methods: We performed an exploratory proteomic analysis in control subjects (n = 23) versus those with type 2 diabetes (T2D) (n = 23) who underwent a hyperinsulinemic clamp study to transient severe hypoglycemia [blood glucose <2.0 mmol/L (36 mg/dl)] in a prospective case-control study. We compared these proteins described as diagnostic and prognostic biomarkers for AIS due to LVO: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE1), thrombospondin-1 (THBS1), pro-platelet basic protein (PPBP), and cadherin 1 (CDH1).Results: At baseline (BL), PPBP (p < 0.05), THBS1 (p < 0.05), and CDH1 (p < 0.01) were elevated in T2D; LYVE1 was not different between controls and T2D subjects at BL or at subsequent timepoints. PPBP and THBS1 tended to increase at hypoglycemia in both cohorts, though reached significance only in controls (p < 0.05), returning to BL levels post-hypoglycemia. CDH1 levels were higher in T2D at BL, at hypoglycemia and up to 2-h posthypoglycemia, thereafter reverting to BL levels.Conclusion: Elevated levels of PPBP, THBS1, and CDH1, circulatory proteins suggested as biomarkers of AIS due to LVO, may, in T2D patients, be prognostically indicative of a cohort of T2D patients at increased risk of ischaemic stroke. Prospective studies are needed to determine if this reflects future clinical risk.Clinical trial reg. no: NCT03102801.

2020 ◽  
Vol 40 (4) ◽  
pp. 555-560 ◽  
Author(s):  
Wisit Chaveepojnkamjorn ◽  
Wandee Boorasri ◽  
Chukiat Viwatwongkasem ◽  
Sukontha Siri ◽  
Warakorn Krienkaisakda

2018 ◽  
Vol 4 (6) ◽  
Author(s):  
Chaveepojnkamjorn W ◽  
Boonrasri W ◽  
Viwatwongkasem C ◽  
Siri S ◽  
Kriengkaisakda W

2016 ◽  
Vol 24 (4) ◽  
pp. 423-430 ◽  
Author(s):  
Ramin Saravani ◽  
Zahra Irani ◽  
Hamid Reza Galavi

Abstract Type 2 diabetes (T2D) is a chronic disorder with different genetics and environmental factors. It is one of growing diseases in the world. Previous studies show association between Transcription Factor 7 Like2 (TCF7L2) and T2D. The current study set to evaluate the relation between TCF7L2 polymorphisms and T2D in Southeast Iran. The present case-control study was done on 250 T2D and 250 healthy controls (HCs). For genotyping polymorphisms TCF7L2 (rs11196205) and (rs4132670) Amplification-Refractory Mutation System-Polymers Chain Reaction (ARMS-PCR) was used. The results showed frequency rates of GC and CC genotypes increased in patients compared to controls (31% vs. 6% and 55% vs. 8%, respectively), showing a statistically significant difference (OR=2.67(1.37-5.21), P<0.05 and OR=3.31(1.92-5.71), P< 0.05, respectively). The C allele was associated with an increased risk of T2D, with the frequency of 28% and 11% in patients and controls, respectively (OR=3.11 (2.22-4.37), P< 0.05). Another Polymorphism of this gene TCF7L2 (rs4132670) was not associated with T2D. Furthermore, the haplotype analysis revealed that rs11196205C/rs4132670C and rs11196205C/rs4132670T are risk factors against T2D (OR=2.08 (1.49-2.86, P<0.05 and OR=1.72 (1.06-2.78) P<0.05, respectively). The findings demonstrated that TCF7L2 (rs11196205) genotypes GC, CC, and allele (C) confer risk for susceptibility to T2D.


2010 ◽  
Vol 163 (3) ◽  
pp. 427-434 ◽  
Author(s):  
José Miguel Dora ◽  
Walter Escouto Machado ◽  
Jakeline Rheinheimer ◽  
Daisy Crispim ◽  
Ana Luiza Maia

ObjectiveThe type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T3) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2.Design and methodsA case–control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms ‘rs225014’ odds ratio (OR) ‘thr92ala’ OR ‘T92A’ OR ‘dio2 a/g’.ResultsIn the case–control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (n=173) versus 12.0% (n=62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03–1.94, P=0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78–2.51)), Grarup (OR 1.09 (95% CI 0.92–1.29)), and Maia (OR 1.22 (95% CI 0.78–1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03–1.36, P=0.02).ConclusionsOur results indicate that in a case–control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a meta-analysis including 11 033 individuals, and support a role for intracellular T3 concentration in skeletal muscle on DM2 pathogenesis.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Liang Ma ◽  
Yongwei Jiang ◽  
Xiaomu Kong ◽  
Meihua Yan ◽  
Tingting Zhao ◽  
...  

The aim of this study was to investigate the relationship between the combined effect of MTHFR C677T (rs1801133) and EPHX2 G860A (rs751141) polymorphism and ischemic stroke in Chinese T2DM patients. This case-control study included a total of 626 Chinese T2DM patients (236 T2DM patients with ischemic stroke and 390 T2DM patients without ischemic stroke). The rs1801133 and rs751141 were genotyped using real-time polymerase chain reaction. Statistical analysis was performed with SPSS 17.0. Results showed that the combined effect of MTHFR TT and EPHX2 GG or GA + AA genotype has a higher risk of ischemic stroke compared with the control group (combined effect of MTHFR CC and EPHX2 GA + AA genotypes; OR = 3.46 and OR = 3.42, resp.; P=.001 and P=.002, resp.). The A allele showed marked association with a lower risk of ischemic stroke in patients with the lowest Hcy levels under additive, recessive, and dominant genetic models (OR = 0.45, OR = 0.11, and OR = 0.44, resp.; P=.002, P=.035, and P=.008, resp.), which was not observed in medium or high Hcy level groups. In conclusion, the T allele of rs1801133 and the G allele of rs751141 may be risk factors of ischemic stroke in the Chinese T2DM population.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Juraj Koska ◽  
Daniel S. Nuyujukian ◽  
Gideon D. Bahn ◽  
Jin J. Zhou ◽  
Peter D. Reaven

Abstract Aims Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia. Materials and methods Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants. Results There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range (< 0.50 nmol/l, HR 1.30 [95%CI 1.05–1.60], p = 0.02) and with rising levels in the high range (> 1.23 nmol/l, 1.27 [1.00–1.63], p = 0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60–0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate − 0.12 [SE 0.01]; ARV, − 0.10 [0.01]) (p < 0.0001 all). The association of low C-peptide levels with CVD risk was independent of cardiometabolic risk factors (1.48 [1.17–1.87, p = 0.001) and remained associated with CVD when tested in the same model with severe hypoglycemia and glucose CV. Conclusions Low C-peptide levels were associated with increased CVD risk in advanced type 2 diabetes. The association was independent of increases in glucose variation or severe hypoglycemia. C-peptide levels may predict future glucose control patterns and CVD risk, and identify phenotypes influencing clinical decision making in advanced type 2 diabetes.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 459-P
Author(s):  
MARIANTHI PAPAGIANNI ◽  
KONSTANTINOS TZIOMALOS ◽  
STAVROULA KOSTAKI ◽  
STELLA-MARIA ANGELOPOULOU ◽  
KONSTANTINOS CHRISTOU ◽  
...  

2021 ◽  
Author(s):  
Navin Kumar Loganadan ◽  
Hasniza Zaman Huri ◽  
Shireene Ratna Vethakkan ◽  
Zanariah Hussein

Aim: This study investigated the incidence of sulfonylurea-induced hypoglycemia and its predictors in Type 2 diabetes (T2D) patients. Patients & methods: In this prospective, observational study, T2D patients on maximal sulfonylurea-metformin therapy >1 year were enrolled. Hypoglycemia was defined as having symptoms or a blood glucose level <3.9 mmol/l. Results: Of the 401 patients, 120 (29.9%) developed sulfonylurea-induced hypoglycemia during the 12-month follow-up. The ABCC8 rs757110, KCNJ11 rs5219, CDKAL1 rs7756992 and KCNQ1 rs2237892 gene polymorphisms were not associated with sulfonylurea-induced hypoglycemia (p > 0.05). Prior history of hypoglycemia admission (odds ratio = 16.44; 95% CI: 1.74–154.33, p = 0.014) independently predicted its risk. Conclusion: Sulfonylurea-treated T2D patients who experienced severe hypoglycemia are at increased risk of future hypoglycemia episodes.


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