scholarly journals The Neoepitopes on Methylglyoxal- (MG-) Glycated Fibrinogen Generate Autoimmune Response: Its Role in Diabetes, Atherosclerosis, and Diabetic Atherosclerosis Subjects

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Shahnawaz Rehman ◽  
Jiantao Song ◽  
Mohammad Faisal ◽  
Abdulrahman A. Alatar ◽  
Firoz Akhter ◽  
...  

Objectives. In diabetes mellitus, hyperglycemia-mediated nonenzymatic glycosylation of fibrinogen protein plays a crucial role in the pathogenesis of micro- and macrovascular complications especially atherosclerosis via the generation of advanced glycation end products (AGEs). Methylglyoxal (MG) induces glycation of fibrinogen, resulting in structural alterations that lead to autoimmune response via the generation of neoepitopes on protein molecules. The present study was designed to probe the prevalence of autoantibodies against MG-glycated fibrinogen (MG-Fib) in type 2 diabetes mellitus (T2DM), atherosclerosis (ATH), and diabetic atherosclerosis (T2DM-ATH) patients. Design and Methods. The binding affinity of autoantibodies in patients’ sera (T2DM, n = 100 ; ATH, n = 100 ; and T2DM-ATH, n = 100 ) and isolated immunoglobulin G (IgG) against native fibrinogen (N-Fib) and MG-Fib to healthy subjects (HS, n = 50 ) was accessed by direct binding ELISA. The results of direct binding were further validated by competitive/inhibition ELISA. Moreover, AGE detection, ketoamines, protein carbonyls, hydroxymethylfurfural (HMF), thiobarbituric acid reactive substances (TBARS), and carboxymethyllysine (CML) concentrations in patients’ sera were also determined. Furthermore, free lysine and free arginine residues were also estimated. Results. The high binding affinity was observed in 54% of T2DM, 33% of ATH, and 65% of T2DM-ATH patients’ samples with respect to healthy subjects against MG-Fib antigen in comparison to N-Fib ( p < 0.05 to p < 0.0001 ). HS sera showed nonsignificant binding ( p > 0.05 ) with N-Fib and MG-Fib. Other biochemical parameters were also found to be significant ( p < 0.05 ) in the patient groups with respect to the HS group. Conclusions. These findings in the future might pave a way to authenticate fibrinogen as a biomarker for the early detection of diabetes-associated micro- and macrovascular complications.

2019 ◽  
Vol 62 (3) ◽  
pp. 109-116
Author(s):  
Reshma Suresh ◽  
Perayil Jayachandran ◽  
Angel Fenol ◽  
Raja Biswas ◽  
Sajitha Krishnan ◽  
...  

Sialic acid (SA), a family of acetylated derivatives of neuraminic acid, an acute phase reactant by itself. It usually occurs as a terminal component at the non-reducing end of carbohydrate chains of glycoproteins and glycolipids. SA participates in multiple physiological functions, such as cell-to-cell interactions, cell migration and proliferation. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by rise in blood glucose level. Periodontitis is a chronic inflammatory disease of the periodontal tissue, leading to destruction of bone surrounding the tooth and ultimately tooth loss. There is a two way relationship between diabetes mellitus and periodontitis. Periodontitis is the sixth complication of diabetes along with retinopathy, nephropathy, neuropathy, macrovascular disease, and altered wound healing. Inflammatory mediators like interleukin-6 and tumor necrosis factor-alpha produced during periodontal inflammation can interfere with the actions of insulin receptors and worsen the glycemic control of diabetic patients. Periodontitis is a major cause of tooth loss, affecting over 300 million people and bacteria associated with periodontitis are also linked with systemic problems like endocarditis, atherosclerosis. Recent work has highlighted a major role for the host sugar sialic acid in the biofilm physiology and host-pathogen interactions of T. forsithya, a key periodontal pathogen. There exists a need for a biomarker, for early detection of disease evolution and more robust therapy efficacy measurements. Serum sialic acids were estimated in Indian population by diphenylamine method and Thiobarbituric acid method. The average values were 68 ± 2.6 mg percent by DPA method and 56 ± 5 mg percent by TBA (thiobarbituric acid assay) method. Age and sex showed no influence on serum sialic acid level. Objectives of the present study was to compare (TSSA) level in healthy subjects, subjects with (CMP) with and without (NIDDM) and its effect on non-surgical periodontal therapy. In the present study, the participants were divided into three groups: Group A, B and C. Group A consists of systemically healthy subjects, Group B consists of subjects with (CMP) while Group C consists of subjects with (CMP) with (NIDDM) and results of this study indicated that, at baseline, there were significant differences between Group A, B and Group C with respect to all the clinical parameters, including (GI), (OHI-S), (PPD), (CAL), (TSSA) and (HbA1c) levels. Thus (TSSA) level could be considered as novel biomarker in the progression of periodontal disease and diabetic status. Periodontitis could be considered as a potential, modifiable, and independent risk factor for the development of diabetes. Early detection of elevated (TSSA) level may help in interpreting the progression of periodontitis, risk of development of diabetes mellitus in future and also to prevent complications.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1830-P ◽  
Author(s):  
GIAN PIO SORICE ◽  
ILARIA IMPROTA ◽  
TERESA MEZZA ◽  
SARA GRIONI ◽  
GIOVANNA MASONE IACOBUCCI ◽  
...  

2020 ◽  
Vol 17 (1) ◽  
pp. 37-54
Author(s):  
Tatyana Chalakova ◽  
Yoto Yotov ◽  
Kaloyan Tzotchev ◽  
Sonya Galcheva ◽  
Boyan Balev ◽  
...  

: Type 1 diabetes mellitus (T1DM) is a chronic disease that starts early in life and often leads to micro- and macrovascular complications. The incidence of the disease is lower than that of type 2 DM and varies in different countries and ethnic groups, and the etiological and pathogenetic factors are different from T2DM. The aim of this overview is to investigate the effect of T1DM on all-cause mortality and CVD morbidity and mortality. During the last decades, the treatment of T1DM has improved the prognosis of the patients. Still, the mortality rates are higher than those of the age- and sex-matched general population. With the prolonged survival, the macrovascular complications and cardiovascular diseases (CVD) appear as major health problems in the management of patients with T1DM. The studies on the CVD morbidity and mortality in this disease group are sparse, but they reveal that T1DM is associated with at least 30% higher mortality. In comparison to healthy people, CVDs are more common in T1DM patients and they occur earlier in life. : Furthermore, they are a major cause for death and impaired quality of life in T1DM patients. The correlation between diabetic control and the duration of T1DM is not always present or is insignificant. Nevertheless, the early detection of the preclinical stages of the diseases and the risk factors for their development is important; similarly, the efforts to improve glycemic and metabolic control are of paramount importance.


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 183
Author(s):  
Anna Izzo ◽  
Elena Massimino ◽  
Gabriele Riccardi ◽  
Giuseppe Della Pepa

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.


2021 ◽  
pp. 112067212110334
Author(s):  
Meng Li ◽  
Gengyuan Wang ◽  
Honghui Xia ◽  
Ziqing Feng ◽  
Peng Xiao ◽  
...  

Objective: To compare the vessel geometry characteristics of color fundus photographs in normal control and diabetes mellitus (DM) patients and to find potential biomarkers for early diabetic retinopathy (DR) based on a neural network vessel segmentation system and automated vascular geometry parameter analysis software. Methods: A total of 102 consecutive patients with type 2 DM (T2DM) and 132 healthy controls were recruited. All participants underwent general ophthalmic examinations, and retinal fundus photographs were taken with a digital fundus camera without mydriasis. Color fundus photographs were input into a dense-block generative adversarial network (D-GAN)-assisted retinal vascular segmentation system ( http://www.gdcerc.cn:8081/#/login ) to obtain binary images. These images were then analyzed by customized software (ocular microvascular analysis system V2.9.1) for automatic processing of vessel geometry parameters, including the monofractal dimension ( Dbox), multifractal dimension ( D0), vessel area ratio ( R), max vessel diameter ( dmax), average vessel diameter ( dave), arc–chord ratio (A/C), and tortuosity (τn). Geometric differences between the healthy subjects and DM patients were analyzed. Then, regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic efficiency of the vascular geometry parameters. Results: No significant differences were observed between the baseline characteristics of each group. DM patients had lower Dbox and D0 values (1.330 ± 0.041; 1.347 ± 0.038) than healthy subjects (1.343 ± 0.048, p < 0.05; 1.362 ± 0.042, p < 0.05) and showed increasing values of dmax, dave, A/C, and τn compared with normal controls, although only the differences in dave and τn between the groups were statistically significant. In the regression analysis, dave and τn showed a good correlation with diabetes ( dave, OR 1.765, 95% CI 1.319–2.362, p < 0.001; τn, OR 9.323, 95% CI 1.492–58.262, p < 0.05). Conclusions: We demonstrated the relationship between retinal vascular geometry and the process in DM patients, showing that Dbox, D0, dave, and τn may be indicators of morphological changes in retinal vessels in DM patients and can be early biomarkers of DR.


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