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Schematic illustration of insulin synthesis by proinsulin cleavage. After formation of proinsulin in the endoplasmic reticulum, proinsulin is packed in granules and split into insulin and C-peptide by limited proteolysis (arrows). Upon stimulation (e.g. by glucose), both peptides are rapidly secreted into circulation at an equimolar ratio. As insulin is rapidly degraded by the liver, insulin concentrations in the peripheral blood are markedly reduced compared to C-peptide concentrations.
Source publication
Harmonization of biomarkers is important for the comparability of laboratory results as it allows the definition of universal reference values and clinical decision limits. In diabetology, immunoassays are widely used to determine HbA1c, C-peptide, insulin, and autoantibodies to beta cell proteins, which are essential biomarkers for the diagnosis a...
Context in source publication
Context 1
... shown in Fig. 8, insulin and C-peptide are well defined on the molecular level. The first insulin immunoassay, a radioimmunoassay (RIA), was described by Yalow and Berson (Yalow and Berson, 1959) and used polyclonal guinea-pig anti-bovine insulin antibodies. However, it could not discriminate between insulin, proinsulin, or different proinsulin ...
Similar publications
Objective. C-peptide is a reliable marker of beta cell reserve and is associated with diabetic complications. Furthermore, HbA1c level is associated with micro- and macro-vascular complications in diabetic patients. HbA1c measurement of diabetic patients with anemia may be misleading because HbA1c is calculated in percent by taking reference to hem...
Citations
... To address this issue, an international agreement has defined the HbA1c measurand as "all haemoglobin molecules having a special hexapeptide in common, which is the stable adduct of glucose to the amino-terminal valine of the haemoglobin β-chain (βN-1-deoxyfructosylhemoglobin)" [23]. Starting from the measurand definition, standardisation efforts led by the National Glycohemoglobin Standardization Program (NGSP) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have been instrumental in establishing consistent reference values and calibration methods, which facilitate the comparability of results across laboratories and testing platforms [24][25][26][27]. There are two principal methods for reporting HbA1c, as follows: the National Glycohemoglobin Standardisation Program (NGSP) method, which expresses values as percentages (%), and the International Federation of Clinical Chemistry (IFCC) method, which reports values in mmol/mol to standardise international measurements [28] and ensure traceability and accuracy, enabling the comparability of results across assay types [29]. ...
Background/Objectives: The determination of glycated haemoglobin (HbA1c) is a cornerstone of the diagnosis and management of diabetes mellitus, serving as a reliable biomarker for assessing long-term glycaemic control. While high-performance liquid chromatography (HPLC) is regarded as the gold standard for HbA1c measurement, its widespread adoption is limited by high costs, operational complexity, and resource requirements. Alternative methodologies, including immunoturbidimetric assays, have garnered interest as practical solutions. This study evaluates the analytical performance of an immunoturbidimetric method for HbA1c determination and its comparability with a validated HPLC method. Methods: The evaluation process was conducted in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The results from 178 human sample leftovers, covering the medical decision range, were compared with those obtained using the HPLC-based Menarini ADAMS A1c HA-8180T system. The analytical performance regarding repeatability and within-laboratory imprecision was also assessed. The probability risk of misinterpreting the analytical results was also calculated. Results: The Passing–Bablok regression indicated a strong correlation between the two methods, with a slope of 1.00 (95% CI: 1.00 to 1.04). The Bland–Altman analysis confirmed minimal systematic differences, showing a mean bias of −0.07% for NGSP and −0.74 mmol/mol for IFCC, both falling within the predefined total allowable error (ATE) limits. Imprecision studies demonstrated excellent repeatability and intermediate precision, with coefficients of variation (CV) ranging from 0.68% to 2.4% across all levels. The risk assessment of diagnostic misinterpretation indicated minimal deviation from an ideal analytical system, in which the measurement uncertainty was regarded as zero. Conclusions: The findings establish the immunoturbidimetric method as a reliable and cost-effective alternative to HPLC for routine HbA1c determination. Its strong analytical performance, combined with operational efficiency, makes it a valuable tool for laboratories, particularly in resource-limited settings, enhancing access to high-quality diabetes monitoring.
... into two categories: type 1 diabetes mellitus (T1DM) is an autoimmune disease that causes the destruction of pancreatic beta cells, whereas type 2 diabetes (T2DM) is much more prevalent and occurs due to a combination of dysfunctional pancreatic beta cells and insulin resistance, leading to impaired glucose regulation over time (1). Figure 1 illustrates the distinct pathological events that result in their development of T1DM and T2DM (2). In 2014, the American Diabetes Association defined T2DM as "a condition characterized by hyperglycemia resulting from the body's inability to use blood glucose for energy...either the pancreas does not make enough insulin or the body is unable to use insulin correctly" (1). ...
The demand for orthodontic treatment among adults has been steadily rising, and it's likely that the adult population will present with more complex dental issues, potentially including chronic conditions like diabetes mellitus. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by insulin deficiency or insulin resistance or both, subsequently leading to a disruption in carbohydrate, fat and protein metabolism. Type I DM or insulin dependent DM (IDDM) is a result of insulin deficiency owing to an autoimmune destruction of pancreatic β cells, more common in younger patients, below 19 years of age; and Type II DM or non-insulin dependent DM (NIDDM) is owing to a resistance in insulin uptake more common in adult patients. Orthodontic tooth movement is a result of complex mechanical loading patterns with consecutive reactions to the periodontal tissues. The orthodontic force applied stimulates the release of multiple biological agents into the local microenvironment ultimately triggering an aseptic inflammatory response leading to local periodontal tissue remodeling. Orthodontic compressive strains on the periodontal ligament and alveolar bone stimulate osteoclastogenesis, and tensile strains on the other side of the tooth, increases the differentiation rate of osteogenic progenitor cells into mature osteoblasts resulting in osteoid deposition. Therefore, for progressive tooth movement to occur in orthodontics, osteoclast-mediated bone resorption occurs in the compressive zone and osteoblast-mediated bone formation takes place in the tension zone. Diabetes mellitus alters the process of bone remodeling that will have an impact on orthodontic tooth movement and ultimately affect treatment goals set out by the orthodontist. The aim of this narrative review is to highlight the mechanisms that DM may have on orthodontic treatment and considerations in managing adult and children orthodontic patients with diabetes.
... The types of diabetes: type 1 diabetes due to insulin secretion and type 2 diabetes due to insulin resistance [69]. B) Pathological events leading to type 1 and type 2 diabetes mellitus [37]. ...
... Immunoassays are the most widely used worldwide and over time have undergone a significant technological evolution ( Figure 1). Through different technologies, immunoassays rely on the ability of antibodies to recognize targets by binding to specific epitopes in complex biological solutions [4]. ...
Introduction
Neurofilament light chain (NfL) is one of the most important biomarkers in the field of clinical neurochemistry. Several analytical methods have been developed in the last decade. Recently, Fujirebio introduced a ready‐to‐use assay kit for measuring NfL levels in the cerebrospinal fluid (CSF) on the fully automated LUMIPULSE G System. In this study, we established the decisional cutoffs for CSF NfL.
Materials and Methods
We performed a retrospective observational study including patients with cognitive decline. CSF NfL levels were measured by two analytical methods: the NF‐light ELISA kit (UmanDiagnostics) and the Lumipulse G1200 fully automated system (Fujirebio). We calculated the cutoffs for the Lumipulse, starting from the consolidated cutoffs of the ELISA method for each age and using the equation obtained by the regression analysis.
Results
The study population consisted of 100 patients with cognitive decline. The median levels of CSF NfL measured by Lumipulse and ELISA were 776.5 ± 772.6 pg/mL and 473.5 ± 443.5 pg/mL, respectively, significantly different (p < 0.001). The Spearman's rank correlation coefficient was 0.962, indicating a robust positive correlation between the two measurement methods. The equation derived from the Passing–Bablok regression analysis was CSF CLEIA = −61.16 + 1.83 × CSF ELISA. Based on this equation, we defined the decisional cutoff values.
Conclusions
Decisional cutoffs are fundamental tools for guiding clinicians to use biomarkers' results and interpretation appropriately. This is the first study establishing the decisional cutoff value of NfL measured by Lumipulse, a fully automated platform widely used in clinical laboratories.
... Beide Peptidhormone sind mit immunologischen Methoden in Heparin-/EDTA-Plasma-Proben oder Serum messbar. Aufgrund der wesentlich längeren in-vivo-Halbwertszeit von C-Peptid im Vergleich zu Insulin, der weitgehenden Resistenz von C-Peptid gegenüber Abbau in hämolytischem Blut und der Messung von C-Peptid in Immunoassays [32], ist die C-Peptidmessung als Surrogat-Parameter der β-Zellfunktion der Insulinmessung im Prinzip überlegen [39]. Allerdings gibt es ein Problem, da die verschiedenen Assays zur C-Peptid-Messung recht unterschiedliche Ergebnisse liefern, es fehlt eine Standardisierung der Messung. ...
... Beide Peptidhormone sind mit immunologischen Methoden in Heparin-/EDTA-Plasma-Proben oder Serum messbar. Aufgrund der wesentlich längeren in-vivo-Halbwertszeit von C-Peptid im Vergleich zu Insulin, der weitgehenden Resistenz von C-Peptid gegenüber Abbau in hämolytischem Blut und der Messung von C-Peptid in Immunoassays [32], ist die C-Peptidmessung als Surrogat-Parameter der β-Zellfunktion der Insulinmessung im Prinzip überlegen [39]. Allerdings gibt es ein Problem, da die verschiedenen Assays zur C-Peptid-Messung recht unterschiedliche Ergebnisse liefern, es fehlt eine Standardisierung der Messung. ...
... ): Pathological events leading to type 1 DM and type 2 DM[27] ...
Diabetes mellitus (DM) is a recurrent trouble found in humans and
animals, especially dogs and cats. Clinical symptoms include
hyperglycemia with glycosuria, and using the documentation of their
persistencefor diagnosis. The insurance that the owners of cats or dogs
have the ability to administer of insulin, perceive the clinical symptoms
of deficiency control DM, and observe of glucose concentrations in
blood, are important steps in the successful management of DM.
Treatment by using insulin twice daily with the diet diversity is very
useful in the management insulin resistance and obesity in dogs. In cats,
the first treatment includes moving to a diet of low-carbohydrates
accompanied by an injection of insulin twice daily. Amnesty rates in cats
can be more than 90%, while in dogs the disease, with the omission of a
bias disorder, is usually life-long. This manuscript aim to detail the
achievable classification, pathogenesis and etiology of impulsive DM in
pet animals and spotlight innovative conducted research in this area.
... In contrast to classical laboratory measured values in diabetology, such as glucose, HbA1c, C-peptide and insulin, which are molecularly precisely defined, islet AABs have a high biological variability. This means that a molecular definition and thus a standardisation are impossible [38,42], Biological variability is due to several factors: ▪ Islet AABs are produced individually by each person and thus differ in their amino acid sequence and therefore in the binding region of the autoantigen. ▪ Islet AABs are polyclonal, i. e. they also differ molecularly within a single person (even in one individual, autoantibodies have a different affinity for the antigen). ...
... CTB-pro-insulin with three furin cleavage sites accumulated in plant seeds has the possibility of in vivo processing (outside the pancreas) in most body cells to produce functional insulin and C-peptide in equimolar concentrations into circulation. C-peptide has been initially considered to have no biological roles, but the experimental data and clinical studies have suggested its significance in the treatment of diabetic complications related to nerve stimulation and renal functions and helps in assessing insulin secretion and insulin resistance [40,41]. CTB fusion with pro-insulin reduces the effective insulin dose for preventing diabetes, which may be due to efficient transmucosal delivery through the gut [5]. ...
The current production of recombinant insulin via fermenter-based platforms (Escherichia coli and yeast) could not fulfill its fast-growing commercial demands, thus leading to a great interest in its sustainable large-scale production at low cost using a plant-based system. In the present study, Agrobacterium tumefaciens-mediated nuclear stable genetic transformation of an industrial oilseed crop, Camelina sativa, to express pro-insulin (with three furin endoprotease cleavage sites) fused with cholera toxin B subunit (CTB) in their seeds was successfully achieved for the first time. The bar gene was used as a selectable marker for selecting transformants and producing herbicide-resistant camelina plants. The transformation process involved the infiltration of camelina inflorescences (at flower buds with partially opened flowers) with A. tumefaciens and harvesting the seeds (T0) at maturity. The T0 seeds were raised into the putative T1 plants sprayed with Basta herbicide (0.03%, v/v), and the survived green transformed plants tested positive for pro-insulin and bar genes. A transformation frequency of 6.96% was obtained. The integration and copy number of the pro-insulin transgene and its expression at RNA and protein levels were confirmed in T1 plants using Southern hybridization, semi-quantitative Reverse Transcriptase-Polymerase Chain Reaction (sqPCR), and quantitative real-time Time PCR (qPCR) and western blot analysis, respectively. Enzyme-linked immunosorbent Assay (ELISA) quantified the amount of expressed pro-insulin protein, and its anti-diabetic efficacy was validated in diabetic rats on oral feeding. Transgenic plants integrated the pro-insulin gene into their genomes and produced a maximum of 197 µg/100 mg of pro-insulin (0.804% of TSP) that had anti-diabetic efficacy in rats.
... There are many applications of immunoassay devices in health, food industry, and clinical applications. Immunoassay devices have been used not only for the detection of bacteria and viruses [7], but also for the measurement of drugs [8] and hormones [9], or for the determination of glucose in urine [10]. ...
In the case of a biological threat, early, rapid, and specific detection is critical. In addition, ease of handling, use in the field, and low-cost production are important considerations. Immunological devices are able to respond to these needs. In the design of these immunological devices, surface antibody immobilisation is crucial. Nylon nanofibres have been described as a very good option because they allow for an increase in the surface-to-volume ratio, leading to an increase in immunocapture efficiency. In this paper, we want to deepen the study of other key points, such as the reuse and stability of these nanofibres, in order to assess their profitability. On the one hand, the reusability of nanofibres has been studied using different stripping treatments at different pH values on the nylon nanofibres with well-oriented antibodies anchored by protein A/G. Our study shows that stripping with glycine buffer pH 2.5 allows the nanofibres to be reused as long as protein A/G has been previously anchored, leaving both nanofibre and protein A/G unchanged. On the other hand, we investigated the stability of the nylon nanofibres. To achieve this, we analysed any loss of immunocapture ability of well-oriented antibodies anchored both to the nylon nanofibres and to a specialised surface with high protein binding capacity. The nanofibre immunocapture system maintained an unchanged immunocapture ability for a longer time than the specialised planar surface. In conclusion, nylon nanofibres seem to be a very good choice as an antibody immobilisation surface, offering not only higher immunocapture efficiency, but also more cost efficiency as they are reusable and stable.
