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.

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.

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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...

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... 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 ...

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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...

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... To reliably evaluate circulating C-peptide concentrations in daily practice, clinical trials, and research studies, a prerequisite is that results of different C-peptide immunoassay measurements should be comparable, i. e., C-peptide immunoassays are standardized [11]. In general, the following assumptions are needed to achieve standardization of a measurand: the biomarker has a well-defined molecular composition, and measurement results are traceable to a primary reference material using a reference management system [12]. ...
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C-peptide is an increasingly used and established marker for beta cell function by assessing endogenous insulin secretion. Accurate and comparable C-peptide measurements are needed in clinical practice and research studies. For example, to calculate HOMA-indices, the C-peptide/glucose ratio, and the classification of recently published novel subgroups of diabetes and prediabetes have used C-peptide measurements. Although the process for standardization of C-peptide measurements is advanced, its full implementation is still missing; therefore, the current status of the comparability of C-peptide measurements using different immunoassays is unclear. Here we compared five widely used C-peptide immunoassays on different analyzers (Abbott ALINITY i, DiaSorin Liaison XL, Roche Cobas e411, Siemens Healthineers ADVIA Centaur XPT, and Immulite 2000 XPi) using serum samples covering the clinically relevant C-peptide concentration range. Although all investigated immunoassays are traceable to the international reference reagent for C-peptide (NIBSC code: 84/510), results of C-peptide measurements showed significant differences between analyzers in the entire concentration range, especially with increasing C-peptide concentrations. The mean bias was largest (36.6%) between results of the immunoassays by Roche and Siemens Healthineers (ADVIA Centaur XPT), and both assays revealed large discrepancies compared to immunoassays by Abbott, DiaSorin, and Siemens Healthineers (Immulite 2000 XPi). In contrast, the three latter assays showed similar C-peptide results (mean bias: 2.3% to 4.2%). Consequently, C-peptide discrepancies might affect clinical diagnosis and the interpretation of study results. Therefore, there is an urgent need to implement and finalize the standardization process of C-peptide measurements to improve patient care and the comparability of research studies.
... [29]. b auch eine Standardisierung unmöglich [29,33]. Die biologische Variabilität beruht auf verschiedenen Faktoren: ▪ Die Insel-AAK werden von den jeweiligen Menschen individuell produziert und unterscheiden sich damit in ihrer Aminosäuresequenz und somit in der Bindungsregion des Autoantigens. ...
... Beide Peptidhormone sind mit immunologischen Methoden in Heparin-/EDTA-Plasma-Proben oder Serum messbar. Auf Grund der wesentlich längeren in vivo-Halbwertszeit von C-Peptid im Vergleich zu Insulin, der weitgehenden Resistenz von C-Peptid gegenüber Abbau in hämolysierten Blut und der besseren labormedizinischen Standardisierung der Messung von C-Peptid in Immunoassays [33], ist die C-Peptid-Messung als Surrogat-Parameter der β-Zellfunktion der Insulinmessung überlegen. ...
... [29]. b auch eine Standardisierung unmöglich [29,33]. Die biologische Variabilität beruht auf verschiedenen Faktoren: ▪ Die Insel-AAK werden von den jeweiligen Menschen individuell produziert und unterscheiden sich damit in ihrer Aminosäuresequenz und somit in der Bindungsregion des Autoantigens. ...
... Beide Peptidhormone sind mit immunologischen Methoden in Heparin-/EDTA-Plasma-Proben oder Serum messbar. Auf Grund der wesentlich längeren in vivo-Halbwertszeit von C-Peptid im Vergleich zu Insulin, der weitgehenden Resistenz von C-Peptid gegenüber Abbau in hämolysierten Blut und der besseren labormedizinischen Standardisierung der Messung von C-Peptid in Immunoassays [33], ist die C-Peptid-Messung als Surrogat-Parameter der β-Zellfunktion der Insulinmessung überlegen. ...
... Orally administered drugs employed in the management of diabetes lead to better patient compliance but may cause side effects such as gastric disturbance and poor renal clearance and generally suffer from lower bioavailability due to poor absorption from Fig. 1 Schematic illustration of glycation in hemoglobin (HbA1C). Reprinted with permission from Ref. [6]. Copyright (2020) Elsevier digestive tract and first pass metabolism in liver. ...
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... However, the following observations make this less likely: (i) sex differences; (ii) parallelism between FPG and HbA 1c ; (iii) individuals at the lower ends of the distributions of FPG (in both sexes) and HbA 1c (in women) showed larger increases than individuals at the upper ends, as shown by Cheng and colleagues [13]. Our single-center analysis was robust, because we measured the parameters in all the samples at a single laboratory, which minimizes measurement bias during the identification of small, but significant changes, especially when the standardization and harmonization of the insulin immunoassays are still in progress [23]. According to a study by Ito of 15,191 Japanese individuals, HbA 1c (%) was equal to 0.0334 × FPG (mg/dL) + 2.26 (R 2 = 0.7321, P < 0.0001) [24]. ...
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... Despite the increasing relevance of insulin and C-peptide measurements, studies have reported discordance among results obtained from different laboratories and different measurement systems; thus, substantial effort has been made to improve their harmonization status [5][6][7][8]. In 1996, the American Diabetes Association found that insulin measurements from different laboratories were widely discordant [9]. ...
Article
Background: Accurate measurements of serum insulin and C-peptide are needed for the therapy and classification of diabetes. This study investigated the status of serum insulin and C-peptide measurements in China by analyzing the results of five pooled serum samples measured in 94 laboratories. Methods: Patient serum samples were pooled into five groups according to insulin and C-peptide concentrations and measured in 94 laboratories using different measurement systems. The inter- and intra-laboratory %CV as well as inter- and intra-measurement system %CV were calculated to assess the status of insulin and C-peptide measurements. To verify whether the disagreement between laboratories was due to different calibrators, as reported in previous studies, one low-level and one high-level sample extracted from the five pooled serum samples were used to recalibrate clinical measurement systems. Results: The mean intra-laboratory, intra-measurement system, inter-laboratory, and inter-measurement system %CVs were 2.7%, 4.8%, 21.8%, and 22.4%, respectively, for insulin and 2.3%, 6.7%, 16.4%, and 24.5%, respectively, for C-peptide. The inter- and intra-laboratory %CVs for insulin decreased with increasing concentration. After recalibration with low- and high-level samples, the mean inter-measurement %CV decreased from 22.4% to 17.2% for insulin and from 24.5% to 5.7% for C-peptide. Conclusions: The intra-laboratory and intra-measurement system imprecision values are satisfactory for serum insulin and C-peptide measurements. However, the results from laboratories using different measurement systems were not comparable, and there is still much work needed to achieve the standardization or harmonization of serum insulin and C-peptide measurements.
... 11,20 Figure 2 presents the results of applying a single conversion factor of 6.00 for the results in The IU unit, namely hormone bioactivity, is commonly adopted in clinical and biological purposes, while the pmol/L unit has priority in metrological measurement systems as it is SI traceable. 8,13,25 The certified values of CRMs are served with SI by assessment of purity and quantification using LC-MS for amino acid analysis via acid hydrolysis, a primary method for protein quantification in terms of metrological hierarchy. 24 The new WHO IS for human insulin (IS 11/212) is also primarily served with an SI-based quantity (mg) with measurement uncertainty, rather than IU. ...
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... T1D is diagnosed by the production of autoantibodies against insulin (especially preproinsulin, GAD65, insulinoma antigen-2 (IA-2) and/or the zinc transporter, ZnT8) (Hörber et al. 2020). These auto antibodies induce oral tolerance but are required in large amounts. ...
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Diabetes mellitus is the most prevalent deadly disease caused by the destruction and dysfunction of pancreatic β cells that consequentially increased blood glucose levels. The management of this disease via external administration of insulin/insulin analogs has been difficult and challenging due to their limited production and accessibility at affordable prices. The conventional insulin production platforms (Escherichia coli, Saccharomyces cerevisiae and mammalian cell lines) with limited scalability and high upstream process costs have not been successful in meeting the rapidly increasing insulin demands. However, plants have been used as safe, scalable, environmentally friendly and cost-effective high capacity production platforms for recombinant orally delivered insulin. Recent technological advances in genome engineering and editing technologies for adequate insulin and insulin analogs production, renewable cellular sources of insulin through transplantation of islets or insulin-producing cells and reprogramming or differentiation of non β cells into β-like cells, used either alone or in combination, for diabetes containment are reviewed here along with their future prospects.
... B. Glucose, HbA1c, C-Peptid und Insulin, die alle molekular genau definiert sind, sind beta-AAK in vieler Hinsicht heterogen. Diese biologische Variabilität macht eine molekulare Definition und deswegen auch eine Standardisierung unmöglich [8]. Eine Vergleichbarkeit der Messwerte muss über eine Harmonisierung angestrebt werden. ...
... Wie aus den obigen Ausführungen zur Problematik bei der Messung von AAK hervorgeht, kann für beta-AAK schon aus biologischen Gründen weder ein definierter Referenzstandard vorhanden sein, noch eine allgemein anerkannte Referenzmethode etabliert werden. Für Testsysteme zur Bestimmung von beta-AAK besteht daher lediglich die Möglichkeit einer Harmonisierung [8]. ...
Article
Zusammenfassung Die Messung von spezifischen Autoantikörpern gegen beta-Zellproteine (beta-AAK) hat in den letzten Jahren das diagnostische Repertoire in der Diabetologie erweitert. Das Vorliegen von beta-AAK kann als erstes Stadium in der Entwicklung eines Typ-1-Diabetes mellitus (DM) gewertet werden, ohne dass Symptome bzw. metabolische Veränderungen vorliegen. Da sich diese oft Jahre vor der klinischen Manifestation in Personen mit hohem Erkrankungsrisiko nachweisen lassen, stellen sie wichtige prädiktive und frühdiagnostische Marker dar. Weiterhin kann die Bestimmung von beta-AAK zur Unterscheidung von Patienten mit einem Typ-1-DM auf der einen und Typ-2-DM und Maturity-Onset Diabetes of the Young (MODY) auf der anderen Seite indiziert sein. Auch für die Differenzialdiagnostik von Patienten mit Insulinmangel aufgrund einer autoimmunen Betazelldestruktion und von Patienten mit klinisch sehr ähnlichem „severe-insulin-deficient“-Diabetes, die aber beide eine unterschiedliche Prognose haben, ist die Antikörperdiagnostik zielführend. Die Abschätzung des Risikos für die Entwicklung eines Typ-1-DM bei Patienten, die an autoimmunen Endokrinopathien leiden, stellt einen weiteren Einsatzbereich für beta-AAK dar. Analytisch sind die beta-AAK mit recht unterschiedlichen Methoden messbar; häufig aber weichen die erhaltenen Messergebnisse bei verschiedenen Testmethoden beträchtlich voneinander ab. Es müssen daher eigene Cut-off Werte vom beauftragten Labor definiert werden, um die erhaltenen Ergebnisse klinisch interpretieren zu können. Zur besseren Vergleichbarkeit der Messergebnisse gibt es derzeit international abgestimmte Harmonisierungsbestrebungen. Für teilnehmende Laboratorien angebotene Ringversuche für die Bestimmungen der Autoantikörper gegen Insulin (IAA), Insulinoma-Antigen 2 (IA-2), Zink Transporter-8 (ZnT8) und Glutamatdecarboxylase (GAD65) können die analytische Qualität ebenfalls verbessern.
... La fructosamina, al igual que la HbA1 C , refleja la concentración media de glucosa, sin embargo, durante menor espacio de tiempo: (últimos catorce a veintiún días), por consiguiente, es más sensible a cambios actuales en el control glucémico. El enorme problema de la fructosamina es sus altas variaciones intraindividuales, lo cual imposibilita valorar las modificaciones en el estado glucémico (Hörber et al., 2020). Actualmente no existen suficientes investigaciones que contemplen a la fructosamina como un marcador en el diagnóstico de la DG. ...
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La obra aborda contenidos relacionados con la diabetes durante el embarazo, para una mejor comprensión de esta patología. La diabetes mellitus gestacional es una enfermedad de enorme trascendencia debido a su creciente prevalencia, asociada a complicaciones maternas, fetales y/o neonatales.