Exploring the Intricacies of Bile Acids: Understanding Their Role in Metabolism and Intrahepatic Cholestasis of Pregnancy
Bile acids (BAs) are fascinating molecules that play a pivotal role in our bodies metabolic processes. From aiding in the digestion of lipids to regulating essential metabolic pathways, BAs have garnered significant interest among researchers and healthcare professionals. In this article, we will delve into the structural and functional aspects of bile acids and explore their significance in a condition called intrahepatic cholestasis of pregnancy (ICP). For additional information, we encourage you to take a look at our latest educational guide: 5th Generation Bile Acids & Intrahepatic Cholestasis of Pregnancy. So, let’s unravel the secrets of bile acids and their impact on our health!
Understanding Bile Acids
Bile acids belong to a diverse family of bile salts, characterised by their planar and amphipathic nature. They possess a hydrophilic hydroxyl and a hydrophobic methyl group, conferring their unique amphipathic properties. These properties allow bile acids to emulsify and solubilize lipids, facilitating their digestion and absorption1.
Bile acids are primarily synthesized in the liver through two pathways: the classic (neutral) pathway and the alternate (acidic) pathway. The classic pathway involves the hydroxylation of cholesterol, while the alternate pathway utilizes oxysterols as precursors. These pathways produce primary bile acids, which are further modified to generate secondary and tertiary bile acids2.
Importance of Bile Acids in Metabolism
Bile acids serve multiple functions in our bodies. Firstly, they emulsify dietary fats, breaking them down into smaller droplets that can be efficiently digested by pancreatic enzymes. Additionally, bile acids are crucial for the absorption of fat-soluble vitamins, such as vitamins A, D, E, and K. These vitamins are incorporated into micelles, facilitated by the presence of bile acids, enabling their uptake3.
Furthermore, bile acids exhibit signalling activity through various receptors, influencing metabolic responses. One key receptor associated with bile acid metabolism is the Farnesoid X receptor (FXR). Activation of FXR regulates bile acid synthesis, delivery, and clearance, maintaining their levels within a safe range. FXR also modulates lipid transport and metabolism, as well as hepatic gluconeogenesis. Another important receptor is TGR5, which influences vasodilation, gallbladder function, and exerts anti-inflammatory effects1.
Intrahepatic Cholestasis of Pregnancy
During pregnancy, the metabolic processes in the liver undergo significant adaptations to accommodate the growing foetus. One condition that can arise during pregnancy is intrahepatic cholestasis, commonly known as ICP. It is a multifactorial disorder characterised by elevated levels of bile acids in the blood, particularly chenodeoxycholic acid (CDCA) and cholic acid (CA)4.
ICP manifests in the second or third trimester and can lead to various symptoms such as pruritus (itching), abnormal liver enzyme levels, jaundice, abdominal pain, and depression. The exact mechanisms underlying ICP are not fully understood, but it is believed that elevated bile acid levels may have adverse effects on the cardiovascular system of the foetus, potentially leading to stillbirth or preterm birth5.
The detection and monitoring of ICP are essential for managing the condition and ensuring the well-being of both the mother and the foetus. Total bile acid (TBA) concentration is a commonly measured parameter to assess the severity of ICP. Monitoring TBA levels can aid in identifying potential risks and enabling timely interventions5.
Introducing the 5th Generation Total Bile Acids Assay
To facilitate the accurate quantification of total bile acids in serum and plasma, the 5th Generation Total Bile Acids Assay has emerged as a reliable and advanced diagnostic tool. This assay utilizes a highly sensitive enzymatic cycling method to measure total bile acid levels, providing precise and reproducible results. With its improved sensitivity and specificity, the 5th Generation Total Bile Acids Assay offers a valuable tool for the early detection and monitoring of intrahepatic cholestasis of pregnancy.
The assay is easy to use and can be incorporated into routine laboratory workflows. It requires a small sample volume, making it convenient for both patients and healthcare professionals. The assay provides rapid results, allowing for prompt diagnosis and timely intervention when necessary.
By accurately quantifying total bile acid levels, the 5th Generation Total Bile Acids Assay aids in assessing the severity of ICP and monitoring the response to treatment. This information is vital for guiding clinical decisions and optimizing patient care during pregnancy.
Furthermore, the assay can contribute to ongoing research on bile acids and their role in ICP. By analysing a larger population and monitoring the dynamics of bile acid levels, researchers can gain deeper insights into the mechanisms underlying this condition and explore potential therapeutic targets.
Assay Principle
Two reactions are combined in this kinetic enzyme cycling method. In the first reaction, bile acids are oxidised by 3-α hydroxysteroid dehydrogenase with the subsequent reduction of Thio-NAD to Thio-NADH. In the second reaction, the oxidised bile acids are reduced by the same enzyme with the subsequent oxidation of NADH to NAD. The rate of formation of Thio-NADH is determined by measuring the specific absorbance change at 405nm. Enzyme cycling means multiple Thio-NADH molecules are generated from each bile acid molecule giving rise to a much larger absorbance change, increasing the sensitivity of the assay.
In conclusion, understanding the intricacies of bile acids is essential for comprehending their impact on our metabolism and health. Intrahepatic cholestasis of pregnancy is a condition that warrants attention, and accurate measurement of total bile acid levels is crucial for its diagnosis and management. The 5th Generation Total Bile Acids Assay offers an advanced and reliable solution for assessing bile acid levels, enabling timely interventions, and improving patient outcomes. With ongoing research and advancements in diagnostic techniques, we can continue to unravel the complexities of bile acids and enhance our understanding of their role in health and disease.
Don’t underestimate the strength of knowledge and awareness. Empower yourself, stay informed, and prioritize your health and well-being!
If you’d like to learn more about Bile Acids and ICP we encourage you to read our new educational guide, 5th Generation Bile Acids & The Importance of Of Intrahepatic Cholestasis of Pregnancy
If you would like an additional information on our 5th Generation Total Bile Acids Assay, or anything else, don’t hesitate to reach out the marketing@randox.com. Additionally, feel free to visit our Reagent resource hub where you will find all of our brochures, support tools and a collection of educational material, to aid you in maintaining the highest possible levels of quality.
References
- McGlone ER, Bloom SR. Bile acids and the metabolic syndrome. Annals of Clinical Biochemistry. 2019;56(3):326-337. doi:https://doi.org/10.1177/0004563218817798
- Chiang JYL, Ferrell JM. Bile Acid Metabolism in Liver Pathobiology. Gene Expression. 2018;18(2):71-87. doi:https://doi.org/10.3727/105221618×15156018385515
- Chiang JYL. Bile Acid Metabolism and Signaling. Comprehensive Physiology. 2013;3(3). doi:https://doi.org/10.1002/cphy.c120023
- Di Mascio D, Quist-Nelson J, Riegel M, et al. Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review. The Journal of Maternal-Fetal & Neonatal Medicine. Published online November 19, 2019:1-9. doi:https://doi.org/10.1080/14767058.2019.1685965
- Piechota J, Jelski W. Intrahepatic Cholestasis in Pregnancy: Review of the Literature. Journal of Clinical Medicine. 2020;9(5):1361. doi:https://doi.org/10.3390/jcm9051361
A Comprehensive Guide to External Quality Assessment Programmes
The importance of External Quality Assessment (EQA) programmes in the realm of medical laboratories is beyond dispute. These programmes serve as external control mechanisms, underpinning the accuracy and reliability of diagnostic tests carried out by laboratories across the globe. By participating in EQA programmes, laboratories gain the ability to monitor their proficiency, identify areas for improvement, enhance their analytical performance, and above all, ensure top-tier patient care.
Today, we find ourselves faced with a multitude of EQA programmes, each touting its own, unique features and benefits. Therefore, the question that naturally follows is – how do you choose the right EQA programme for your laboratory?
Understand Your Laboratory’s Requirements
The first step towards selecting an EQA programme is to clearly understand the requirements of your laboratory. These requirements could encompass the range of tests performed, the desired frequency of assessment, and the specific areas where your lab wishes to improve
Examine the EQA Programmes
The next step is to critically examine each EQA programme. Look at the range of tests they cover, the frequency of their assessments, the type of samples they use, and their approach towards feedback and improvement.
Reporting
One of the most critical aspects of an EQA programme is the results reporting mechanism. This mechanism should provide comprehensive and constructive feedback, highlighting areas of improvement, and offering guidance on how to enhance performance. It is also essential to consider the frequency of reporting. More frequent reporting allows laboratories to identify problems and implement corrective actions swiftly, aiding in the continuous improvement of a laboratory and the confident delivery of accurate patient results.
Accreditation
The accreditation of the EQA programme should also be evaluated. Superior programmes are accredited to ISO17043:2010. Participation in an accredited EQA programme is mandatory under ISO15189:2022 accreditation. Choosing a scheme accredited to ISO17043 ensures that the programme has been rigorously evaluated and meets the necessary criteria of a high-quality EQA programme.
Cost-effectiveness
The cost of the EQA programme should be compared to the benefits your laboratory will reap from participating in the scheme. Although cost should not be the sole determining factor, it’s a crucial element to consider. Factors such as consolidation and number of registrations are key areas where many providers differ.
Customer Support
Finally, it’s vital to consider the customer support provided by the EQA programme. Adequate support will ensure that any issues or queries are addressed in a timely and efficient manner
Our latest educational guide Choosing the Right EQA Programme has been constructed to help you with this decision. Providing more detail on the points discussed above and more, this guide displays how the world-renowned RIQAS EQA programmes can help you maximise the accuracy of your laboratory results and achieve ISO15189:2022 accreditation.
In conclusion, selecting the right EQA programme requires a careful and thorough evaluation of several factors. By taking the time to understand your laboratory’s needs, scrutinising each EQA programme, and considering factors such as reporting, accreditation, cost, and customer support, you can make a well-informed decision that will significantly enhance the proficiency of your laboratory and the quality of patient care.
Remember, the primary objective of an EQA programme is to help your laboratory improve. Therefore, the right EQA programme for your laboratory is the one that best assists you in achieving this objective.
Prostate-specific Antigen & Prostate Cancer
Prostate cancer is the most common form of cancer in men. In the UK, 1 in every 8 men will be diagnosed with the condition within their lifetime, resulting in around 12’000 deaths per year1. Prostate-specific antigen is a major protease found in semen which functions to cleave semeogelins into smaller polypeptides resulting in the liquefication of semen2.
This week, we had the pleasure of welcoming Dr Floris Helmich, who discussed laboratory imprecision relating to Prostate-specific antigen (PSA) and prostate cancer in our latest webinar. Dr Helmich took the time out of his busy schedule to present his experience in PSA quantification and the importance of quality control in yielding accurate and precise results as well as discussing some of the experimental techniques he has found useful in identifying the source of bias laboratory testing. Dr Helmich also discussed the ambiguity relating to reporting ranges and how bias can affect the results of laboratory PSA testing.
What is PSA?
PSA is an enzyme produced by the prostate ductal and acinar epithelium where it is secreted into the lumen before it is used to liquefy semen. Once PSA enters circulation, most are bound to protease inhibitors, however, some remain inactive and circulate in the lumen as free PSA2.
PSA levels in men vary depending on their age. Typically, men between the ages of 50 and 69 should have a PSA level below 3ng/ml. If the PSA concentration exceeds 3ng/ml, it could be a potential indicator of prostate cancer3. However, the challenge with using PSA as the sole monitoring method for prostate cancer is the relatively high false positive rate associated with it. A higher PSA concentration can also be attributed to conditions such as an enlarged prostate, prostatitis, or a urinary tract infection4.
Research indicates that 1 out of 4 men with elevated PSA levels will actually have prostate cancer. Additionally, it has been observed that approximately one in every seven men diagnosed with prostate cancer will maintain normal PSA levels3. These findings highlight the limitations of relying solely on PSA screening for prostate cancer diagnosis. As a result, some countries have started to limit their recommendations regarding PSA-based prostate cancer diagnosis.
In response to these limitations, other countries have chosen to maintain their recommendations for PSA testing but are augmenting the guidelines by incorporating additional criteria to ensure more accurate diagnoses.
Elevated PSA
Elevated levels of PSA should not always be automatically interpreted as a sign of prostate cancer. In older men, one common cause of elevated PSA is benign prostatic hyperplasia (enlarged prostate). Additionally, prostatitis, which refers to inflammation of the prostate, can contribute to an increase in PSA concentration3. It’s important to consider other potential factors that can lead to elevated PSA levels, such as urinary tract infections, recent sexual activity, natural age-related increases, or injury to the groin area5.
Therefore, when assessing PSA levels, it is crucial to recognize that various non-cancerous conditions can also result in elevated PSA. It is recommended to consult healthcare professionals who can evaluate the individual’s medical history, perform further diagnostic tests, and consider other clinical factors to accurately determine the underlying cause of elevated PSA and make informed decisions about the next steps in diagnosis and treatment.
Ultra-low PSA concentrations
The diagnostic accuracy of PSA concentration for prostate cancer is known to be limited. However, there is a clear association between PSA levels and prostate cancer, which confirms it as a valuable tool for risk stratification and diagnosis when used in conjunction with other established factors.
PSA testing also plays a crucial role in monitoring patients who have undergone treatment for prostate cancer. In cases where the patient is deemed cancer-free, their PSA levels should decrease to within the normal range. Following radical prostatectomy (removal of the entire prostate), PSA levels should ideally be undetectable. Post-radiotherapy, it is expected that PSA levels will reach their lowest point (nadir) within 12-18 months. However, it’s important to note that in some cases, a temporary spike in PSA concentration has been observed after radiotherapy. This spike should not be immediately interpreted as recurrent cancer, but these patients should be closely monitored.
If PSA concentrations rise above 2.0ng/ml after radiotherapy, further testing is recommended to assess the possibility of recurrent cancer. Close monitoring and additional evaluations will help healthcare professionals make accurate and timely decisions regarding the patient’s ongoing treatment and care6
Guidelines
Different countries offer varying guidance in relation to Ultra-low PSA testing. The table below details some of these recommended guidelines:
| Guidelines | Description |
| American Urology Association 7 | PSA concentrations of >0.2ng/ml, followed by a subsequent confirmatory >0.2ng/ml result should be considered biochemical recurrence. However, a cut-off of 0.4ng/ml may better predict metastatic relapse. |
| European Association of Urology8 | A detectable PSA indicating relapse should be differentiated from a clinically meaningful relapse. PSA thresholds that predict further metastasises are:
Post-RP = >0.4ng/ml Post-RT = nadir + 2ng/ml |
| Prostate Cancer Foundation1 | Post-RP = PSA 0.2ng/ml is indicative of biochemical recurrence
Post-RT = PSA nadir + 2ng/ml is indicative of biochemical recurrence |
Randox Ultra-low PSA Control
We are excited to introduce Randox’s latest innovation, the Ultra-low PSA Control, designed to assist in the precise quantification and monitoring of ultra-low levels of PSA in post-therapy prostate cancer patients. This control has been specifically optimized for use on Roche systems, ensuring exceptional performance and compatibility. Moreover, it is versatile enough to be utilized on various other platforms, making it the sole control available on the market for measuring ultra-low levels of PSA across a range of instruments.
With the Acusera Ultra-low PSA Control, healthcare professionals can achieve accurate and reliable results, enabling them to monitor the progress and treatment response of prostate cancer patients with heightened sensitivity. With a clinically relevant concentration of approximately 0.055ng/ml, this advancement in control technology contributes to enhanced patient care and supports medical professionals in making informed decisions regarding treatment adjustments or further interventions.
Randox’s commitment to innovation and precision in diagnostic solutions continues with the Ultra-low PSA Control, empowering laboratories to deliver high-quality and dependable PSA measurements, even at the ultra-low levels required for post-therapy monitoring.
Take a look at our webinar, Laboratory Imprecision in Relation to PSA and Prostate Cancer Follow-up, with Dr Floris Helmich to learn about how his clinical laboratory deals with bias at quality control relating to Ultra-low PSA quantification
If you’d like to learn more about PSA testing and prostate cancer, we encourage you to read our new educational guide, Ultra-low PSA and Prostate Cancer
If you would like an additional information on our Ultra-low PSA Control, or anything else relating to Quality Control, don’t hesitate to reach out the marketing@randox.com. Additionally, feel free to visit our QC resource hub where you will find all of our brochures, support tools and a collection of educational material, to aid you in maintaining the highest possible levels of quality.
References
- Prostate Cancer Foundation. About prostate cancer. Prostate Cancer UK. Published 2023. https://prostatecanceruk.org/prostate-information-and-support/risk-and-symptoms/about-prostate-cancer
- Balk SP, Ko YJ, Bubley GJ. Biology of Prostate-Specific Antigen. Journal of Clinical Oncology. 2003;21(2):383-391. doi:https://doi.org/10.1200/jco.2003.02.083
- NHS Choices. Should I have a PSA test? – Prostate cancer. NHS. Published 2019. https://www.nhs.uk/conditions/prostate-cancer/should-i-have-psa-test/
- Isono T, Tanaka T, Kageyama S, Yoshiki T. Structural Diversity of Cancer-related and Non-Cancer-related Prostate-specific Antigen. Clinical Chemistry. 2002;48(12):2187-2194. doi:https://doi.org/10.1093/clinchem/48.12.2187
- Mejak SL, Bayliss J, Hanks SD. Long Distance Bicycle Riding Causes Prostate-Specific Antigen to Increase in Men Aged 50 Years and Over. Steyerberg EW, ed. PLoS ONE. 2013;8(2):e56030. doi:https://doi.org/10.1371/journal.pone.0056030
- Santis D, Gillessen S, Grummet J, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer.; 2023.
- AUA. Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline (2020) – American Urological Association. www.auanet.org. Published 2023. https://www.auanet.org/guidelines-and-quality/guidelines/advanced-prostate-cancer
- Sindhwani P, Wilson CM. Prostatitis and serum prostate-specific antigen. Current Urology Reports. 2005;6(4):307-312. doi:https://doi.org/10.1007/s11934-005-0029-y
Acusera 24·7 Software Updates v3.3
Randox Quality Control is thrilled to announce the release of our latest software update for Acusera 24·7, which includes a collection of new features to enhance your user experience and create a more effective quality management system for your laboratory. This update shall take place on Tuesday 20th June 2023. Below, you’ll find details of the latest software updates and how these changes can help you improve your daily QC activities.
Events
- Users can now add an event at the assay, instrument or QC levels to allow more accurate monitoring of control events. In addition, this feature adds the capability to record reagent lot changes.
- Users now have the ability to temporarily hide all events from the interactive charts, allowing for a clearer view of QC performance over a selected timeframe.
Uncertainty of Measurement
- User can now add the uncertainty of the calibrator value to the uncertainty of measurement report to provide a more accurate assessment of uncertainty.
- Users now have the ability to hide the intraprecision data from the uncertainty of measurement report if no data has been entered for this field.
Charts
- A selection of new interactive charts have been added to this software. These charts focus on the individual results per analyte that each instrument generates over a specified time period.
Individual results
This graph displays a spread of the individual results for a single machine, per analyte generated over a specified time.
Weekly Count
This Bar Chart shows the weekly count of quality control results for a specific instrument, assay and lot.
Instrument Comparison
Users can now view a line graph, which plots the weekly mean of results from multiple instruments using the same assay and QC lot, allowing a comprehensive overview of your QC data.
If you’d like to learn more about these updates, we encourage you to watch our new Acusera 24·7 video guides: Acusera 24.7 Video Guides
This software update will be live from Tuesday 20th June 2023. To make the upgrade process as smooth as possible, we encourage Acusera 24·7 users to clear their browser cache, visit the Acusera 24·7 site, and you will be ready to avail of these new features!
If you would like an additional information on these updates, or anything else relating to Acusera 24·7, don’t hesitate to reach out the marketing@randox.com. Additionally, feel free to visit our QC resource hub where you will find all of our brochures, support tools and a collection of educational material, to aid you in maintaining the highest possible levels of quality.
Enhancing Laboratory Quality Control with Multi-Rule QC: A Comprehensive Guide
Introduction
We are thrilled to announce the release of our latest educational guide, “Understanding Multi-rule QC,” which delves into the world of laboratory quality control. Designed for laboratory professionals, this comprehensive guide aims to empower you with knowledge and strategies to ensure accurate results and uphold patient safety.
Understanding the Significance of Multi-Rule QC
Laboratory quality control is paramount in maintaining the integrity of test results. The guide begins by exploring the various causes of deviations in laboratory testing processes. From instrument malfunctions to environmental factors, we shed light on potential sources of error that can impact result accuracy.
Next, we dive into the core of the guide: Multi-rule QC. This powerful framework encompasses a series of rules that serve as a robust screening tool for identifying outliers, shifts, and trends in data. Through an in-depth exploration of rules such as 1:2s, 1:3s, 2:2s, R4s, 3:1s, 4:1s, 10x, and 7T, we unveil their underlying principles and their significance in maintaining quality control within laboratory settings.
Applying the Multi-Rule QC Approach
The guide equips laboratory professionals with practical insights on applying the Multi-rule QC approach. By examining consecutive data points, analysing trends, and detecting systematic shifts, you gain the ability to proactively address issues before they compromise result accuracy. We highlight the importance of avoiding overreliance on individual rules for result rejection, emphasizing the need to consider additional factors such as clinical relevance and method performance.
Troubleshooting Out-of-Control Events
No laboratory is immune to out-of-control events. That’s why our guide goes beyond rule implementation and delves into effective troubleshooting strategies. We provide guidance on identifying root causes, implementing corrective actions, and re-establishing control in your laboratory environment. By embracing a culture of continuous improvement, you can minimize the impact of deviations and optimize laboratory performance.
Acusera 24.7
Acusera 24.7 is a cloud-based inter-laboratory data management and peer-group reporting software designed to assist in the management of daily QC activities and aid continuous improvement in the laboratory. It includes multi-rule capabilities that can be utilized to monitor your QC data and index it as accepted, rejected, or trigger an alert, depending on the pre-defined multi-rules against which you want to check your data. These features enable the identification of nonconformities and reduce the need for laborious manual statistical analysis while enhancing the accuracy and precision of the laboratory.
Conclusion
In an era where accuracy and patient safety are paramount, the “Multi-rule QC” guide serves as an invaluable resource for laboratory professionals. By mastering the principles and applications of Multi-rule QC, you can enhance the quality control processes within your laboratory, mitigating risks and delivering reliable test results.
To explore the full potential of Multi-rule QC and embark on a journey of laboratory excellence, we invite you to download the guide today. Stay ahead of the curve and ensure the highest standards of quality and patient care in your laboratory!
You can download the Understanding Multi-rule QC Educational Guide below:
If you’d like to find out more about what we can do to help your laboratory or view our range of Internal Quality Controls, don’t hesitate to contact us at marketing@randox.com or feel free to browse the range on our website https://www.randox.com/laboratory-quality-control-acusera/.
Differentiating Type 1 and Type 2 Diabetes Mellitus
An estimated 422 million people across the world are living with diabetes1. Diabetes Mellitus (DM) encompasses a collection of chronic diseases characterised by absent or ineffective insulin activity. Insulin is a hormone produced by the pancreas responsible for a host of essential physiological processes related to glucose metabolism and protein synthesis.
There are two main forms of DM, named type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) which result from different mechanisms and more importantly, require different therapeutic approaches. It is estimated that up to 40% of those diagnosed with T2DM after the age of 30 may have been misdiagnosed2. This misdiagnosis of T1DM as T2DM will result in poor glycaemic control, frequent healthcare contact for increased treatment, inappropriate insulin regimes and risk of life-threatening ketoacidosis.
In this article, we’ll look at the similarities and differences between these two forms of DM and investigate the mechanisms by which these common diseases arise.
Insulin Pathway
The normal insulin signalling pathway, shown below, is responsible for the processing and transport of glucose in the body. Briefly, insulin binds to the insulin receptor and activates PI3K and, subsequently, serine-threonine kinase (AKT). AKT is responsible for the phosphorylation of glycogen synthase kinase 3-β (GSK-3β), inhibiting its activity and promoting the synthesis of glycogen leading to a reduction in blood glucose concentration. Failing to inhibit GSK-3β will result in hyperglycaemia and eventually T2DM.
Type 1 Diabetes Mellitus
T1DM is most commonly diagnosed at a young age. This form of DM is the result of an autoimmune reaction to proteins produced by the pancreas which results in a lack of insulin secretion. The antibodies responsible for this autoimmunity are detailed in the table below:
A key factor in T1DM pathogenesis is changes in the T cell-mediated immunoregulation, notably in the CD4+ T cell compartment. The activation of the CD4+ T cells is responsible for inflammation of the pancreatic cells which produce insulin, known as insulitis.
Changes in the expression of IL-1 and TNFα cause structural alterations in pancreatic β-cells which result in the suppression of insulin secretion. This insulin deficiency has subsequent effects on glucose metabolism and protein synthesis.
T1DM causes an increase in hepatic glucose levels when gluconeogenesis converts glycogen to glucose. A lack of insulin means the subsequent hepatic uptake of this glucose does not occur.
Insulin is also responsible for regulating the synthesis of many proteins. This regulation can be positive or negative but ultimately results in an increase in protein synthesis and a decrease in protein degradation. Therefore, when hypoinsulinemia occurs, decreasing insulin concentration in the blood, protein catabolism is increased leading to increased plasma amino acid concentration.
Type 2 Diabetes Mellitus
The pathogenesis of T2DM, detailed in the diagram below, is multi-factorial. It arises from a combination of genetic and environmental factors which affect insulin activity.
In T2DM, the regulatory mechanisms related to glucose metabolism fail resulting in impaired insulin activity or insulin resistance.
Mutations in genes involved in insulin production can cause the secretion of abnormal insulin molecules, known as insulinopathies. Insulinopathies are unable to effectively metabolise glucose which results in the accumulation of this sugar. Additionally, obesity is considered to be a causal factor in the development of T2DM.
Unlike those with T1DM, patients with T2DM can maintain circulating insulin levels. T2DM is characterised by glucose intolerance, impaired glucose tolerance, diabetes with minimal fasting hyperglycaemia, and DM in association with overt fasting hyperglycaemia.
Individuals with impaired glucose tolerance have hyperglycaemia despite preserving high levels of plasma insulin. These levels of insulin decline from impaired glucose tolerance to DM. It is insulin resistance is considered the primary cause of T2DM.
Misdiagnosis
The misdiagnosis of these types of DM is common, due to similar symptoms. The simplest differentiating factor is when these symptoms manifest. T1DM is an autoimmune disorder and therefore, symptoms generally occur much earlier in one’s life. T2DM is typically diagnosed in later life. The common symptoms of DM are:
- Frequent urination, particularly throughout the night.
- Polydipsia (excessive thirst)
- Polyphagia (excessive hunger)
- Lethargy
- Sudden weight loss
- Genital itching or thrush
- Blurred vision
The misdiagnosis of T2DM as T1DM results in unnecessary initial insulin therapy, higher drug and monitoring costs and often, an increase in the number and severity of symptoms. Conversely, the incorrect classification of T1DM as T2DM causes poor glycaemic control, frequent visits to healthcare services for treatment, inappropriate insulin regimes and risk of Diabetic Ketoacidosis.
Diabetic Ketoacidosis (DKA)
DKA is a potentially life-threatening condition caused by an accumulation of ketones in the body due to insulin deficiency, which is common in patients with T1DM, however, an increasing number of cases have been reported in patients with T2DM. Diagnosis of DKA consists of a high anion gap metabolic acidosis, ketone bodies present in serum and/or urine, and high blood glucose concentration. The symptoms of DKA include:
- Polyuria (excessive urination) and polydipsia (thirst)
- Weight loss
- Fatigue
- Dyspnoea (shortness of breath)
- Vomiting
- Fever
- Abdominal pain
- Polyphagia (excess hunger)
- Fruity-smelling breath caused by acetone accumulation.
Randox Type 1 Diabetes Mellitus Genetic Risk Array
T1DM is largely genetic and is associated with over 50 distinct genetic signatures, many of which are single nucleotide polymorphisms (SNPs). This is of great advantage in testing as unlike traditional biomarkers, genetic markers don’t change throughout one’s life, providing a robust method for diagnosis and risk stratification. Genetic data gathered can then be used to develop a genetic risk score, allowing an individual’s probability of developing the disease to be quantified.
Using this principle, together with our patented Biochip array technology, Randox have developed a T1DM GRS array. Using a combination of 10 SNPs from the HLA region and the non-HLA region commonly detected in T1DM patients, and a selection of other risk factors and biomarkers, this molecular array can accurately discriminate between T1DM and T2DM.
Conclusions
Misdiagnosis of DM can have life-threatening consequences. Both types of DM are very common and distinguishing between T1DM and T2DM is crucial.
T1DM is an autoimmune disorder with a lack of insulin secretion, while T2DM is primarily due to insulin resistance. Understanding their mechanisms is vital for accurate diagnosis and treatment. Genetic testing, like the Randox Type 1 Diabetes Mellitus Genetic Risk Array, can differentiate between T1DM and T2DM by analysing genetic markers and providing personalized treatment insights.
Accurate diabetes diagnosis is crucial for proper management, prevention of complications, and improving the lives of millions. Together, we can make a difference in the lives of those affected by diabetes!
If you’d like to learn more about the different types of DM, including the pathogenesis, pathophysiology, associated risk factors, and more, please take a look at our educational guide Diabetes Solutions.
Alternatively, feel free to reach out to our marketing team at marketing@randox.com who will be happy to help you with any queries you may have.
References
- World Health Organization. Diabetes. World Health Organisation. Published April 5, 2023. Accessed April 25, 2023. https://www.who.int/news-room/fact-sheets/detail/diabetes
- The Misdiagnosis of type 1 and type 2 diabetes in adults. The Lancet Regional Health. 2023;29:100661-100661. doi:https://doi.org/10.1016/j.lanepe.2023.100661
World Haemochromatosis Awareness Week
World Haemochromatosis Awareness Week, took place this year between the 1st – 7th June.
Genetic Haemochromatosis, or the ‘Celtic Curse’ is the UK and Ireland’s most inherited condition.
Randox can help you find out if you are at risk with a blood test from one of our Randox Health clinics, including our newly opened Clinic in Sandyford, Dublin.
The tests are available from £69 and the results of which will be returned within 7-14 days. Randox’s easy-to-interpret Genetic Haemochromatosis risk report will provide a breakdown of your results and what they mean.
An optional remote appointment with a Randox genetic counsellor can also be made when booking. Early diagnosis enables early treatment to prevent ill health because of iron overload.
Haemochromatosis is a condition which causes people to absorb too much iron from their diets but many people are not aware of it despite over 9 million people in the UK estimated to have the genetic predisposition to haemochromatosis (or Iron overload disorder.)
Despite its commonplace, this condition is rarely diagnosed with only one in every five thousand receiving a diagnosis.
Symptoms can Include:
• Fatigue
• Palpitations
• Joint Pain
• Abdominal Pain
• Skin Pigmentation
Haemochromatosis is an Autosomal Recessive disorder.
These type of disorders usually mean that men and women are equally likely to be affected, with Haemochromatosis however, men are more likely to be at risk than women.
Women may be protected from iron overload due to physiological blood loss (menstruation and pregnancy) which can reduce the iron overload.
Men living with haemochromatosis are ten-times more likely to be at risk of liver cancer and have twice the risk of developing dementia, if left undiagnosed or untreated.
Follow the link below to book: Haemochromatosis Test
AACC 2023
We will be exhibiting at 2023 AACC!
We invite you to stop by the Anaheim Convention Center between July 25 and July 27, 2023 for a visit.
With over four decades of experience in the medical diagnostics industry, Randox is dedicated to enhancing global health outcomes. As a provider of high-quality diagnostic solutions, Randox offers a wide range of products and services, including Quality Control, Molecular Diagnostics, Third Party Reagents, Point of Care, and Clinical Chemistry Analysers.
Meet The Team
If you plan to attend 2023 AACC, our Product Specialists Team will be available at Booth #3223 to answer any questions you may have. To ensure the most productive use of your time, we recommend scheduling a meeting with one of our Randox representatives in advance to discuss your specific needs and book a time slot during the event by clicking on the button below:
Sexually Transmitted Infections – Rapid Testing at the Point of Care
Urgency, Challenges and Advances in STI Testing
Sexually transmitted infections (STIs) are a major global health issue, with over 30 pathogens causing an estimated one million infections daily, a number that is rising. Surveillance programs in countries like the United States and Canada have reported an increase in STIs such as syphilis, gonorrhoea, and chlamydia. STIs can have serious consequences for sexual health, including infertility and chronic pelvic pain, particularly affecting women. The World Health Organization (WHO) has recognised the urgency of addressing this problem and has recommended measures to end the STI healthcare issue by 2030. Integrated testing, including multiplex and point-of-care testing, is considered essential. However, implementation of these recommendations at regional and national levels is lacking. Rapid point-of-care PCR tests that can detect multiple pathogens simultaneously would greatly improve STI diagnosis and containment. Currently, Randox, in collaboration with Bosch offers two STI test panels on the Vivalytic POC system: Vivalytic STI and Vivalytic MG, MH, UP/UU panels, capable of detecting multiple pathogens in a single test run, with results available within hours.
The Global Burden
- The WHO estimates 374 million new infections of chlamydia, gonorrhoea, syphilis, and trichomoniasis annually.
- Chlamydia is the most frequently reported STI in Europe, followed by gonorrhoea and syphilis.
- Countries with comprehensive STI screening programs, like Denmark, have higher prevalence rates than the European average.
- The UK has a comprehensive screening program for chlamydia targeting 15-24-year-olds, with cases accounting for 60% of total cases in the European Region.
- The actual infection rate in countries without systematic screening is likely higher than official figures suggest.
- Reported cases of gonorrhoea and syphilis in the European Region have increased, particularly among certain age groups and higher numbers in men than women.
Gaps in Current STI Testing Strategies
The European Centre for Disease Prevention (ECDC) acknowledges the growing concern of STIs in Europe and emphasises the importance of testing in their recent report. While various European countries have screening programs for chlamydia, testing options for other STI pathogens are usually limited. The lack of accessible testing, combined with the prevalence of asymptomatic infections, increases the risk of STI transmission and hampers containment efforts. Prevention campaigns and low-threshold testing opportunities are crucial to address the spread of STIs. The UK’s chlamydia screening program, implemented in 2008, demonstrated the benefits of community-based testing services and led to a significant increase in diagnosed cases, reducing the number of unreported cases.
Infections and Co-Infections
- Co-infections, where multiple sexually transmitted pathogens are present simultaneously, are common but often go undetected due to limited testing.
- Symptoms of co-infections can be difficult to differentiate since different pathogens can cause similar or overlapping symptoms.
- However, most STIs, even in high-risk groups, are caused by a single sexually transmitted pathogen.
- In cases where co-infections need to be detected, a rapid and comprehensive differential diagnosis of sexually transmitted pathogens is crucial for initiating appropriate therapy promptly.
The Importance of Rapid Results at the Point of Care
- Rapid detection and treatment of STIs are crucial to prevent further spread.
- Traditional STI diagnostics in specialized laboratories can result in delays of several days or up to 1-2 weeks until test results are available to the physician.
- Delays occur due to transportation of samples, laboratory workflow, result transfer, and scheduling additional appointments.
- The delay in treatment initiation can lead to decreased patient compliance and missed appointments.
The Vivalytic STI test provides results directly at the point of care (POC) in less than two and a half hours. It eliminates the need for sample transportation to a central laboratory. In addition, patients can receive their test results on the same day of the visit, allowing for immediate initiation of appropriate treatment.
In a Nutshell
Sexually transmitted infections (STIs) spread due to various factors. Many STIs do not show symptoms, resulting in numerous unreported and untreated cases that can have fatal consequences depending on the specific pathogen. Increasing awareness and implementing a decentralised low-threshold testing strategy can significantly reduce infections, particularly among high-risk groups. Speed and comprehensive testing of relevant pathogens are crucial for targeted therapy and containing STIs. Rapid PCR tests used at the point of care (POC) are emerging as important technologies due to their advantages. Patients receive same-day results and immediate treatment, providing clarity in just one visit. Clinicians can provide up-to-date diagnoses and treatments, even in decentralised or hospital settings, benefiting high-risk patients with limited access to healthcare.
Vivalytic
The Bosch Vivalytic, is an advanced and automated platform for molecular diagnostics that utilises PCR to detect pathogens. It offers applications for various medical disciplines and requires only a few steps from sample collection to obtaining results. The patient sample is processed automatically within the Vivalytic analyser, and the test result is displayed on its integrated screen. The time it takes to get results depends on the specific Vivalytic application. For the STI Panel, which simultaneously detects 10 common sexually transmitted pathogens, the time to result is 2.5 hours. On the other hand, the Vivalytic MG, MH, UP/UU panel, used to detect mycoplasmas and/or ureaplasmas, provides results in approximately one hour.
By conducting fully automated analyses at the point of care, Vivalytic saves valuable time for hospitals, labs, genitourinary clinics and doctor’s offices during their routine processes.
| STI Panel | MG, MH, UP, UU Panel |
|---|---|
| Chlamydia trachomatis | Mycoplasma genitalium |
| Neisseria gonorrhoeae | Mycoplasma hominis |
| Trichomonas vaginalis | Ureaplasma parvum/Ureaplasma |
| Mycoplasma genitalium | |
| Treponema pallidum | |
| Mycoplasma hominis | |
| Ureaplasma urealyticum | |
| Haemophilus ducreyi | |
| Herpes simplex virus I | |
| Herpes simplex virus II |
At a Glance
- The Vivalytic system allows fully automated sample analysis with minimal manual steps.
- It eliminates the need for expensive and complex laboratory equipment.
- Vivalytic supports both single and multiplex tests.
- The Vivalytic does not require peripheral equipment such as a laptop, keyboard, barcode scanner, or charging station.
- The cartridge used in the system ensures hygienic and safe operation as a closed system.
- Cartridges can be stored and used at room temperature.
- Vivasuite, a cloud-based solution, facilitates convenient device management.
- The Vivalytic can be seamlessly integrated into existing IT structures using HL7, Ethernet, USB, or WLAN.
For more information please contact us at: marketing@randox.com
Internal Quality Control and ISO 15189
As a major contributor to the IVD industry, like many of you, the trials and tribulations of quality control are an everyday consideration. It is for this reason we strive to make the process of IQC as straightforward as possible. We recognise how busy life in the laboratory can get and believe it is our duty to simplify your QC process as much as possible.
The Acusera range has been designed with this in mind. Our true third-party control range boasts unrivalled levels of consolidation, supplied at clinically relevant concentrations in a suitable, commutable matrix. When used in combination with Acusera 24.7, our interlaboratory management software, the Acusera range will help to reduce analytical errors and maximise precision in your laboratory.
With the recent updates to ISO 15189:2022, we understand that there will be added pressure on many laboratories who are trying to maintain their accreditation. To assist you with your gap analysis and transition to these updated standards, we have produced this accreditation guide, detailing all of the key points relating to this new version of the highly sought after accreditation.
If you’d like to find out more about what we can do to help your laboratory or view our range of Internal Quality Controls, don’t hesitate to contact us at marketing@randox.com or feel free to browse the range on our website https://www.randox.com/laboratory-quality-control-acusera/.
