The Correlation Between Liver Cirrhosis and Lactic Acidosis
The Correlation Between Liver Cirrhosis and Lactic Acidosis
Lactic acid is an organic compound which produces the conjugate base lactate through a dissociation reaction. Due to it being a chiral compound, two optical isomers of lactate exist; D-Lactate and L-Lactate. The lactate dehydrogenase (LDH) enzyme can produce and metabolise both isomer forms to pyruvate, however due to the isomer-specific nature of LDH different forms of the enzyme are required. D-Lactate requires a D-LDH form whereas L-Lactate requires L-LDH. As a result of this requirement, combined with the fact that mammalian cells only contain L-LDH, the lactate produced in humans is almost exclusively L-Lactate.
One of the roles of L-Lactate is its involvement in the Cori Cycle, a metabolic pathway involved in the production of glucose. The cycle involves the rotatory transportation of lactate and glucose from the liver and the muscle. Lactate is produced in the muscle through glycolysis which is then transported to the liver through the blood stream. In the liver, the lactate is oxidised to pyruvate and then converted to glucose by gluconeogenesis, which is then transported back to the muscle for the process to start again. 1500 mmol of lactate is produced daily by the body and is cleared at a constant rate via the liver.
Problems can arise if the liver fails to regulate the lactate produced. Hyperlactamia is the name given to elevated levels of lactate in the body, as a result of the rate of production exceeding the rate of disposal. This is due to a lack of oxygen that reduces blood flow to the tissues. If levels continue to rise a patient is at risk of lactic acidosis.
The liver is an important tissue in the regulation of lactate, it is therefore no surprise that liver damage can prevent this process resulting in a further diagnosis of lactic acidosis. A healthy liver is a vital part of lactate regulation as it acts as the main consumer of lactate and contributes to 30-40% of lactate metabolism. Potential victims are patients who suffer with cirrhosis, a complication of liver disease, which is commonly caused by alcohol abuse and viral Hepatitis B and C.
Patients with liver cirrhosis have a higher risk of increased lactate levels. Increased levels of the lactate ions disturbs the acid-base equilibrium, causing a tilt towards lactic acidosis. The mortality rate of patients who develop lactic acidosis is high, prompt recognition and treatment of the underlying cause remain the only realistic hope for improving survival.
The Randox L-Lactate reagent allows for a prompt and accurate diagnosis of lactic acidosis.
Randox L-Lactate Reagent
The Randox L-Lactate key benefits include:
- Excellent working reagent stability of two weeks when stored at + 15 – +25°C
- Exceptional correlation of r = 0.99 when compared against other commercially available methods
- A wide measuring range of 0.100 – 19.7 mmol/l and so is capable of detecting abnormal levels in a sample
- Colorimetric method
- Lyophilised reagents for enhanced stability
Securing the future with in vitro diagnostic tests
The aim of Biomedical Science Day is to raise the public’s awareness of the importance of biomedical science and the vital role it plays in the world. Randox are dedicated to improving healthcare worldwide through placing a major focus on research and development. The Randox scientists work in pioneering research into a range of common illnesses such as cancer, cardiovascular disease and Alzheimer’s disease.
A recent blog from Doris-Ann Williams, the Chief Executive at BIVDA, explains how “increased funding is not enough to sustain the NHS” and how “we need to make better use of in vitro diagnostics to ensure a successful future”.
The National Health Service (NHS) is a publicly funded, primarily taxation, national healthcare system in the United Kingdom. It was first set-up on July 5th, 1948 by Aneurin Bevan as he believed that everyone, regardless of wealth, should have access to good healthcare. Whilst the NHS is an extremely important aspect of healthcare in the UK, in vitro diagnostics are the heart and soul of the healthcare system as healthcare professionals not only rely on blood tests to diagnose and treat patients, but also to rule out the different contributing causes to a disease state. In vitro diagnostics also plays a key role in monitoring chronic disease states. In vitro diagnostics can also aid in reducing hospital stays, reduce misdiagnosis and support patients in looking after their own health and to deliver personalised treatment plans.
The Randox scientists have developed several niche assays to improve patient diagnosis, monitor treatment and eliminate misdiagnosis.
Adiponectin is a protein hormone secreted by adipocytes with anti-inflammatory and insulin-sensitising properties. It plays an important role in a number of metabolic processes including glucose regulation and fatty acid oxidation. Adiponectin levels are inversely correlated with abdominal visceral fat which have proven to be a strong predictor of several pathologies, including: metabolic syndrome, type 2 diabetes mellitus (T2DM), cancers and cardiovascular disease (CVD). For more information on the importance of testing Adiponectin levels, check out our Adiponectin Whitepaper.
Cystatin C is an early risk marker for renal impairment. The most commonly run test for renal impairment is Creatinine. Creatinine measurements have proven to be inadequate as certain factors must be taken into consideration, including age, gender, ethnicity etc. The National Institute for Health and Care Excellence (NICE) have updated their guidelines, which now recommends Cystatin C as a more superior test for renal impairment due to its higher specificity for significant disease outcomes than those based on Creatinine. For more information on the importance of testing Cystatin C levels, check out our Cystatin C Whitepaper.
Small-dense LDL Cholesterol (sdLDL-C)
LDL Cholesterol (LDL-C) consists of two parts: the large and buoyant LDL Cholesterol and the small and dense LDL Cholesterol. Whilst all LDL-C transports triglycerides and cholesterol to bodily tissues, their atherogensis varies according to their size. As sdLDL-C is small and dense, they can more readily permeate the arterial wall and are more susceptible to oxidation. Research indicates that individuals with a predominance of sdLDL-C have a 3-fold increased risk of myocardial infarction. It has been noted that sdLDL-C carries less Cholesterol than large LDL, therefore a patient with predominately sdLDL-C particle may require nearly 70% more sdLDL-C particles to carry the same amount of cholesterol as the patient with predominately LDL-C particles. For more information on the importance of testing sdLDL-C levels, check out our sdLDL-C Whitepaper.
These three niche in vitro diagnostics tests developed by Randox scientists can aid in reducing NHS costs due to their higher performance compared to the traditional tests. Randox are constantly striving to improve healthcare worldwide.
For more information on the extensive range of Randox third-party in vitro diagnostic reagents, visit: https://www.randox.com/diagnostic-reagents/ or contact email@example.com.
Homocysteine & Women’s Health
Homocysteine is a thio-containing amino acid produced by the intracellular demethylation of methionine. Elevated levels of homocysteine (hyperhomocysteinemia) is more common in women than in men and is associated with a wide array of illnesses. It has also been proven to cause several problems in women including: cardiovascular disease (CVD), colon cancer, pregnancy complications, and birth defects.
Elevated levels of circulating homocysteine correlates with an increased risk of vascular occlusion (blockage of a blood vessel). Hyperhomocysteinemia can cause inflammation of the endothelium (thin layer of cells linking the interior blood vessels). Failure to lower homocysteine levels can cause further inflammation of the arteries, veins, and capillaries causing atherosclerosis. Consequently, blood and oxygen supply to tissues is reduced, increasing the risk of cardiovascular disease. Elevated levels correlates with higher diastolic and systolic blood pressure, hypertension. However, this correlation is stronger in women than in men. Women with elevated levels of homocysteine have a 3-fold increased risk of CVD, whereas men have a 2-fold increased risk.
Women with hyperhomocysteinemia have an increased risk of colorectal cancer than women with lower levels. Women who present with the highest levels of homocysteine have more than a 70% increased colorectal cancer risk. A correlation between reduced levels of folate and increased levels of homocysteine have been found in women with colorectal adenoma. It is recommended that women with hyperhomocysteinemia and reduced levels of folate should increase their intake of fruit and vegetables to reduce their levels of homocysteine and increase their levels of folate.
Pregnancy Complications and Birth Defects
Homocysteine levels should decline during pregnancy, however, in some cases, levels increase. Hyperhomocysteinemia is associated with foetal neural tube defects which causes various conditions, characterised by placental vasculopathy, including pre-eclampsia, abruption, and recurrent pregnancy loss. It has been identified that folate supplementation can half the risk of foetal neural tube defects. One study found that hyperhomocysteinemia was associated with a 2-fold to 3-fold increased risk for pregnancy-induced hypertension, abrupyio placentae, and intrauterine growth restriction.
Randox Homocysteine Reagent
The Randox Homocysteine assay offers a few unique features:
- Limited interference from Bilirubin, Haemoglobin, Triglycerides, and Intralipid, producing more accurate and precise results.
- Two-reagent format for convenience and ease of use
- Calibrator provided with kit, simplifying the ordering process
Other features include:
- Liquid ready-to-use reagents – for optimum user experience
- Excellent linearity – 47. 9 μmol/L, ensuring abnormally high levels of homocysteine are detected.
- Enzymatic method
- Tri-level cardiac control available
Rheumatoid Arthritis and Women’s Health
Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterised by pain, swelling and stiffness in joints which commonly affects the hands, wrists and feet. Whilst both men and women can suffer from rheumatoid arthritis, it is more commonly seen in women than men.
Rheumatoid arthritis is the most common autoimmune disease with a higher prevalence rate compared to lupus, multiple sclerosis, type 1 diabetes, Crohn’s disease and psoriasis.
The incidence rates of rheumatoid arthritis differ between men and women. The onset of RA occurs much earlier for women, for most, during their 30’s and 40’s. In an American study, it was noted that the incidence rates peak for women around the ages of 55 to 64, compared to 75 to 84 years of age for men.
As most women are diagnosed with rheumatoid arthritis in their 30’s and 40’s, a study found that the diagnosis negatively impacts both the body and mind of women, as indicated in their pain, disease activity, and quality of life scores. This is due to women being diagnosed at a time when their burdens are the heaviest as this is the time when women are most likely to have children or are raising children combined with work and socialising.
Changes in hormone levels also impacts women. It has been noted that before a menstrual period, women find the symptoms of rheumatoid arthritis to be more severe, but settles during their cycle. Also, due to the changes in hormone levels during pregnancy, 50 – 60% of women with rheumatoid arthritis noticed that their symptoms improved.
The key to managing rheumatoid arthritis is to start the treatment as early as possible as it can halt or slow the disease, preventing joint damage and complications, including: osteoporosis and cardiovascular disease. Rheumatoid arthritis increases the risk of heart attack by 60%. To start treatment as early as possible, it is important that it is diagnosed as early as possible.
Randox offer a number of key assays for the diagnosis of rheumatoid arthritis.
Rheumatoid factor is the most routinely run test to diagnose rheumatoid arthritis as 80% of rheumatoid arthritis patients test positive for rheumatoid factor. The Randox Rheumatoid Factor reagent offers the following benefits:
- Wide measuring range of 6.72 – 104lU/ml for the accurate measurement of clinically important results
- Accurate assessment of rheumatoid factor titre (calibrant standardised against primary WHO material; 1st British Standard 64/2)
- No interference from complement C1q
- Automated immunoturbidimetric assay
- Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings
It has been found that complement C4 and CRP upregulation indicates the middle to late stages of rheumatoid arthritis.
The Randox Complement C4 reagent offers the following benefits:
- Wide measuring of 3.41 – 152mg/dl for the accurate measurement of clinically significant results
- Limited interferences from Bilirubin, Haemoglobin, Intralipids, and Triglycerides, producing more accurate results
- Automated immunoturbidimetric assay
- Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings
The Randox High-Sensitivity CRP reagent offers the following benefits:
- Wide measuring of 0.477 – 10mg/l fir the accurate measurement of clinically significant results
- Liquid ready-to-use reagents for convenience and ease of use
- Applications available for a wide range of biochemistry analysers, detailing instrument-specific settings
Lp(a): For the Accurate Detection of CVD Risk
Lp(a) is an independent risk factor for cardiovascular disease (CVD), even when classical risk factors such as hypertension, elevated cholesterol, and diabetes have been taken into consideration. High levels of Lp(a) is a heredity condition, associated with complex mechanisms involving the proatherogenic and prothrombotic pathways (1).
Traditional CVD testing panel
According to the World Health Organisation (WHO), CVD is the leading cause of death globally, accounting for 31 percent of deaths, totalling 17.7 million deaths per year. 80 percent of all CVD deaths are attributed to heart attacks and strokes, equivalent to 1 in 4. Identifying those who are at a high risk of developing CVD and ensuring that they are receiving the appropriate treatment can prevent premature deaths (2).
The lipid profile is frequently used to assess an individual’s risk of CVD developing later in life. Routine tests to assess CVD risk include: triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). LDL-C has been found to strongly correlate with CVD risk (3). NICE recommend measuring total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides as the full lipid profile and then review other risk factors, including: age, diet, smoking, QRISK, co-morbidities to view risk and the management of risk (4). However, the current lipid panel needs to be adjusted to ensure that its utilisation is effective in meeting clinician and patient needs.
Lipoprotein (a) or Lp(a) consists of two protein molecules, apolipoprotein (a) or apo(a) is covalently linked by a disulphide bond to the apolipoprotein B-100 or apoB-100 of a cholesterol-rich low-density lipoprotein or LDL like particle. Lp(a) is synthesised in the liver and is detectable in the bloodstream (5).
The structure of Lp(a) resembles that of the proteins involved in the breakdown of blood clots, plasminogen and tissue plasminogen activator (TPA). As a result, the biggest concern with Lp(a) is that it prohibits the ability of these proteins to break down blood clots by competing for the ‘binding to fibrin’, boosting the blood’s clotting ability within arteries, thus heightening the risk of heart attacks and strokes. Consequently, high levels of Lp(a) is characterised by atherosclerosis including coronary heart disease, peripheral vascular disease, aortic stenosis, thrombosis and stroke (6).
The Journal of the American Medical Association reviewed 36 studies in 2009 which assessed ‘the role of Lp(a) and vascular disease’ in 126,634 individuals. The study found that a 3.5-fold increase in Lp(a) levels was accompanied with a 13 percent higher risk of coronary heart events and a 10 percent higher risk of stroke (7).
Later, an Italian population study carried out on 826 individuals in 2014 found that elevated levels of Lp(a) is due to two different variations of the apo(a) gene which is determined by the kringle sequence differences at the apo(a) locus. The study found that individuals with one variation had a 50 percent greater risk of CVD, while individuals with both variations had 2.5 times greater risk (7).
According to the Lipoprotein Foundation (2015), based on genetic factors, from birth, one in five or 20% of individuals have high Lp(a) levels greater than 50mg/dL, with most blissfully unaware they have it. Overtime, high levels of Lp(a) gradually narrow the arteries, limiting blood supply to the brain, heart, kidneys and legs, increasing the risk of heart attacks and strokes (5).
Testing for high Lp(a) levels
The Lipoprotein (a) Foundation (2015) recommends that Lp(a) levels should be tested if:
- There is a family history of cardiovascular disease including stroke, heart attack, circulation problems in the legs and/or narrowing of the aorta, at a young age
- Stroke or heart attack if classical risk factors including high LDL-cholesterol, obesity, diabetes and smoking have been eliminated
- High levels of LDL-cholesterol following treatment with statins or other LDL lowering medications(5)
When selecting a Lp(a) assay, the Internal Federation of Clinical Chemistry (IFCC) (2004) Working Group on Lp(a) recommends that laboratories use assays that do not suffer from apo(a) size-related bias to minimise the potential risk of misclassification of patients for coronary heart disease (8).
The Lp(a) Foundation reference Marcovina and Albers (2016) in their recommendations for the best Lp(a) test. The study came to the following conclusions:
- Robust assays based on the Denka method, reportable in nanomoles per litre (nmol/L) are traceable to WHO/IFCC reference material
- Five-point calibrators with accuracy-based assigned target values will minimise the sensitivity of to the size of apo(a)
- Upon request, manufacturers should provide the certificate of evaluation of the calibrator and reagent lots with the relative expiration dates (9)
Benefits of the Randox Lp(a) assay
The Randox Lp(a) assay is one of the only methodologies on the market that detects the non-variable part of the Lp(a) molecule and so suffers minimal size related bias providing more accurate and consistent results. This methodology allows for the detection of Lp(a) in serum and plasma. The Randox Lp(a) kit is standardized to the WHO/IFCC reference material, SRM 2B, and is the closest in terms of agreement to the ELISA reference method.
A five-point calibrator is provided with accuracy-based assigned target values which accurately reflects the heterogeneity of isoforms present in the general population.
Liquid ready-to-use reagents are more convenient as the reagent does not need to be reconstituted, reducing the risk of errors.
Applications are available for a wide range of biochemistry analysers which details instrument-specific settings for the convenient use of the Randox Lp(a) assay on a variety of systems. Measuring units in nmol/L are available upon request.
- Li, Yonghong, et al. Genetic Variants in the Apolipoprotein(a) Gene and Coronary Heart Disease. Circulation: Genomic and Precision Medicine. [Online] October 2011. [Cited: April 24, 2018.] http://circgenetics.ahajournals.org/content/4/5/565.
- World Health Organisation. Cardiovascular Disease. [Online] 2017. [Cited: April 30, 2018.] http://www.who.int/cardiovascular_diseases/en/.
- Doc’s Opinion. Lipoprotein (a). [Online] 2013. [Cited: April 30, 2018.] https://www.docsopinion.com/health-and-nutrition/lipids/lipoprotein-a/.
- National Institutional for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification. [Online] July 2014. [Cited: April 30, 2018.] https://www.nice.org.uk/guidance/cg181/chapter/1-recommendations#lipid-modification-therapy-for-the-primary-and-secondary-prevention-of-cvd-2.
- Lipoprotein(a) Foundation. Understand Inherited Lipoprotein(a). [Online] 2015. [Cited: April 24, 2018.] http://www.lipoproteinafoundation.org/?page=UnderstandLpa.
- Heart UK. Lipoprotein (a). [Online] June 23, 2014. [Cited: April 24, 2018.] https://heartuk.org.uk/files/uploads/huk_fs_mfss_lipoprotein_02.pdf.
- Ashley, Robert. High lipoprotein(a) levels may indicate heart disease in some. The Brunswick News. [Online] March 05, 2018. [Cited: April 24, 2018.] https://thebrunswicknews.com/opinion/advice_columns/high-lipoprotein-a-levels-may-indicate-heart-disease-in-some/article_16ab1049-7a6f-5da0-8966-59e94ae31b6d.html.
- Dati, F; Tate, J R; Marcovina, S M; Steinmetz, A; International Federation of Clinical Chemistry and Laboratory Medicine; IFCC Working Group for Lipoprotein(a) Assay Standardization. First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay–Lp(a) SRM 2B. NCBI. [Online] 2004. [Cited: April 30, 2018.] https://www.ncbi.nlm.nih.gov/pubmed/15259385.
- Tsimikas, Sotirios. A Test in Context: Lipoprotein(a) – Diagnosis, Prognosis, Controversies, and Emergining Therapies. 6, s.l. : Elsevier, 2017, Vol. 69. 0735-1097.
Metabolism: how Randox is helping to diagnose metabolic conditions
Many people talk about their metabolism as if it is a muscle or organ they can somehow control. In reality, your metabolism refers to a series of chemical processes in each cell that turn the calories you eat into fuel to keep you alive.
Metabolism is the biochemical process of combining nutrients with oxygen to release the energy our bodies need to function. Your resting metabolic rate (RMR) is the number of calories your body burns to maintain vital body functions such as heart rate, brain function and breathing. RMR accounts for up to 75 percent of the calories you burn each day. Knowledge of your individual RMR is a critical piece of information to appropriately establish daily calorie needs.
The body’s major organs — the brain, liver, kidneys, and heart — account for about half of the energy burned at rest, while fat, the digestive system, and especially the body’s muscles account for the rest.
Did you know?
Approximately 20-25% of the world’s adult population have metabolic syndrome?
A common misconception surrounding metabolic health is that it refers solely to your weight, and if you are overweight you are considered to be unhealthy. But in actual fact this may not be entirely true. Good metabolism means that your body is in good overall health, which doesn’t account for just your weight! Common metabolic disorders include genetic metabolic disorders, diabetes and metabolic syndrome. Understanding and testing to see how well your metabolism is functioning is key to ensuring long lasting health.
There are a number of genetic metabolic disorders caused by mutations of single genes. Examples of common disordersinclude Gaucher’s disease, hemochromatosis and cystic fibrosis. Gaucher’s disease is a genetic disorder that affects the body’s ability to break down fat that can accumulate in the liver/spleen and bone marrow. Hemochromatosis is a condition that is caused by the over-absorption and build-up of iron while cystic fibrosis is a metabolic disorder that appears as a result of a build-up of mucus in lungs/liver and intestines. Each of these metabolic disorders affect certain organs from functioning properly and therefore your overall healthiness.
Type 2 diabetes is one of the most common types of metabolic disorders in the world that is expected to affect 592 million people by 2035. It is characterised by high blood sugar, insulin resistance or a lack of insulin being produced by the pancreas. Insulin resistance occurs when the body isn’t able to use insulin the right way which increases blood glucose levels. Insulin is needed for cells to take in glucose (sugar) from the bloodstream and convert it into energy. Over time this lack of insulin can damage the organs in your body.
Metabolic syndrome (also known as syndrome X, Reaven’s syndrome, and CHAOS) is not a disease but a collection of risk factors that affect your health; these include high blood pressure, high blood sugar/cholesterol and abdominal fat. Left untreated, these risk factors, together, can lead to long term serious problems including an increased risk of heart disease, stroke and developing type 2 diabetes.
Can you improve your metabolic health?
Yes! The good news is that if you discover that your metabolic health is not up to scratch you can improve it through a combination of diet, exercise and lifestyle adjustments such as:
- 30 minutes of moderate to intense exercise 5-7 times a week
- Low-dose aspirin to reduce your risk of stroke or heart attack
- Quit smoking
- Medication for blood pressure/cholesterol/ blood sugar
- Limit alcohol intake
- Eat a healthy balanced diet
Randox has developed the RX series of clinical chemistry analysers for superior semi-automated and fully automated testing. The RX series extensive dedicated test menu goes beyond routine testing and has many unique and high-performance tests available. Our range of tests covers several parameters to assess your overall metabolic health.
Metabolic Health Profile
|Alkaline Phosphatase||C02 Total||Sodium|
|AST (GOT)||Glucose||Total Protein|
The RX series clinical chemistry analysers provide laboratories with a robust and smart solution ensuring you maintain a consistent workflow and can provide accurate results first time, every time. Offering excellent customer support services, our trained engineers are on hand to work with you in preserving the continuity of your operations while maximising the potential of your RX series instrument.Our world-famous test menu of high quality reagents ensures excellence in patient care, guaranteeing unrivalled precision and accuracy reducing costly test re-runs or misdiagnosis and offering complete confidence in results.
For more information visit: https://www.randox.com/clinical-chemistry-analysers/
Could there be 5 types of diabetes?
A peer-reviewed study, published in The Lancet Medical Journal suggests there are five types of diabetes. Could diabetes be more complex than we once thought? Could diabetes be segmented into five separate diseases?
What is diabetes?
Diabetes is an incurable disease which prohibits the body’s ability to produce and respond to insulin. Currently, diabetes is classified into two main forms, type 1 and type 2.
Type 1 diabetes is an autoimmune disease which manifests in childhood. In type 1 diabetes, the body’s white blood cells attack the insulin-producing cells in the pancreas. As a result, individuals with Type 1 diabetes rely on the injection of insulin for the remainder of their lives.
Type 1 diabetes affects 10 percent of individuals with diabetes. 96 percent of children diagnosed with diabetes have type 1. Type 1 diabetes in children is commonly diagnosed between the ages of 10 and 14. The prevalence of type 1 diabetes in children and young people (under the age of 19) is 1 in every 430-530 and the incidence of type 1 in children under 14 years of age is 24.5/100,000 (Diabetes UK, 2014).
Type 2 diabetes is the result of insulin resistance, meaning that the pancreas does not produce enough insulin or the body’s cells do not respond to the insulin produced. As type 2 diabetes is a mixed condition, with varying degrees of severity, there are a few methods to manage the disease, including dietary control, medication and insulin injections.
Type 2 diabetes is the most common form of diabetes, affecting 90 percent of individuals with diabetes, and has now become a global burden. The global prevalence of diabetes has almost doubled from 4.7 percent in 1980 to 8.5 percent in 2014, with a total of 422 million adults living with diabetes in 2014. It is expected to rise to 592 million by 2035. In 2012, diabetes accounted for 1.5 million deaths globally with hypertension causing a further 2.2 million deaths. 43 percent of these deaths occurred before 70 years of age. Previously type 2 diabetes was commonly seen in young adults but is now commonly seen in children as well. In 2017, 14% more children and teenagers in the UK were treated for diabetes compared to the year before (World Health Organization, 2016).
In both forms of diabetes, hyperglycemia can occur which can lead to number of associated complications including renal disease, cardiovascular disease, nerve damage and retinopathy.
The novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables – peer-review study
This new research studied 13,270 individuals from different demographic cohorts with newly diagnosed diabetes, taking into consideration body weight, blood sugar control and the presence of antibodies, in Sweden and Finland.
This peer-reviewed study identified 5 disease clusters of diabetes, which have significantly different patient characteristics and risk of diabetic complications. The researchers also noted that the genetic associations in the clusters differed from those seen in traditional type 2 diabetes.
Cluster One – Severe autoimmune diabetes (SAID)
SAID is similar to type 1 diabetes. SAID manifests in childhood, in patients with a low BMI, have poor blood sugar and metabolic control due to insulin deficiency and GADA. 6% of individuals studied in the ANDIS study were identified with having SAID.
Cluster Two – Severe insulin-deficient diabetes (SIDD)
SIDD is similar to SAID, however, GADA is negative. This means that the characteristics of SIDD are the same as SAID, young, of a healthy weight and struggled to make insulin, however, SIDD is not the result of an autoimmune disorder as no autoantibodies are present. Patients have a higher risk of diabetic retinopathy. 18% of subjects in the ANDIS study were identified with having SIDD.
Cluster Three – Severe insulin-resistant diabetes (SIRD)
SIRD is similar to that of type 2 diabetes and is characterised by insulin-resistance and a high BMI. Patients with SIRD are the most insulin resistant and have a significantly higher risk of kidney disease, and microalbuminuria, and non-alcoholic fatty liver disease. 15% of subjects in the ANDIS study were identified as having SIRD.
Cluster Four – Mild obesity-related diabetes (MOD)
MOD is a mild form of diabetes which generally affects a younger age group. This is not characterised by insulin resistance but by obesity as their metabolic rates are close to normal. 22% of subjects in the ANDIS study were identified as having MOD.
Cluster Five – Mild age-related diabetes (MARD)
MARD is the most common form of diabetes manifesting later in life compared to the previous four clusters. Patients with MARD have mild problems with glucose regulation, similar to MOD. 39% of subjects in the ANDIS study were identified with having MARD.
This new sub-classification of diabetes could potentially enable doctors to effectively diagnose diabetes earlier, through the characterisation of each cluster, including: BMI measurements, age, presence of autoantibodies, measuring HbA1c levels, ketoacidosis, and measuring fasting blood glucose levels. This will enable a reduction in the incidence of diabetes complications and the early identification of associated complications, and so patient care can be tailored, thus improving healthcare (NHS, 2018) (The Week, 2018) (Ahlqvist, et al., 2018) (Collier, 2018) (Gallagher, 2018).
The Randox diabetes reagents cover the full spectrum of laboratory testing requirements from risk assessment, using our Adiponectin assay, to disease diagnosis and monitoring, using our HbA1c, glucose and fructosamine assays, to the monitoring of associated complications, using our albumin, beta-2 microglobulin, creatinine, cystatin c, d-3-hydroxybutyrate, microalbumin and NEFA assays.
Whilst this study is valuable, alone it is not sufficient for changes in the diabetes treatment guidelines to be implemented, as the study only represents a small proportion of those with diabetes. For this study to lead the way, the clusters and associated complications will need to be verified in ethnicities and geographical locations to determine whether this new sub-stratification is scientifically relevant.
Ahlqvist, E. et al., 2018. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. [Online]
Available at: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30051-2/fulltext?elsca1=tlpr
[Accessed 16 April 2018].
Collier, J., 2018. Diabetes: Study proposes five types, not two. [Online]
Available at: https://www.medicalnewstoday.com/articles/321097.php
[Accessed 16 April 2018].
Diabetes UK, 2014. Diabetes: Facts and Stats. [Online]
Available at: https://www.diabetes.org.uk/resources-s3/2017-11/diabetes-key-stats-guidelines-april2014.pdf
[Accessed 16 April 2018].
Gallagher, J., 2018. Diabetes is actually five seperate diseases, research suggests. [Online]
Available at: http://www.bbc.co.uk/news/health-43246261
[Accessed 16 April 2018].
NHS, 2018. Are there actually 5 types of diabetes?. [Online]
Available at: https://www.nhs.uk/news/diabetes/are-there-actually-5-types-diabetes/
[Accessed 16 April 2018].
The Week, 2018. What are the five types of diabetes?. [Online]
Available at: http://www.theweek.co.uk/health/92048/what-are-the-five-types-of-diabetes
[Accessed 16 April 2018].
World Health Organization, 2016. Global Report on Diabetes, Geneva: World Health Organization.
The Importance of Equine Health
With the Grand National around the corner, Randox Reagents have investigated the importance of equine health, focusing on racehorses.
Maintaining good health in racehorses is vital as proper management can reduce the incidence of many disease conditions. Racehorses are bred, raised, and trained to perform as athletes. Therefore, it is vital that the performance health of racehorses is continually assessed to ensure that they are physically fit, happy and healthy.
Racehorse’s have a busy life. They are broken in from 18 months of age, usually using traditional methods such as long reining, followed by accepting a rider and training alongside other horses. At 2 years of age, the real training begins which focuses on fitness and speed rather than ‘schooling’ the horse in the conventional way. This training is undertaken alongside another horse to teach the trainee horse how to race but at the same time, it is taught to settle and listen to the jockey.
In peak season, the horse’s weekly exercise regime consists of: two days of fast gallop work with steady trotting or cantering the rest of the week, with a rest day on Sunday’s (depending on races scheduled for the horse).
The most important bodily systems for top athletic performance in racehorses include:
Skeletal system (including bone, tendons and ligaments) problems such as torn or stretched ligaments or tendons or a broken bone will be very painful, inducing lameness and prohibiting performance
Muscles enable the horse to perform. Fatigued or damaged muscles will result in poor performance as the horse cannot generate enough energy and strength to maintain its high performance
Respiratory system (nasal passages, throat and lungs) problems prohibits the normal flow of oxygen through the body, which prohibits the energy required for exercise
Cardiovascular system (heart, blood vessels, volume of blood and red blood cells) problems prohibits the movement of oxygen from the lungs to the muscles, again prohibiting the generation of energy required for exercise.
Central nervous system (CNS) problems can result in the loss of coordination and the fine control that accompanies minor problems to the CNS can significantly prohibit exercise performance
Due to the intense training that racehorses undergo, it is vitally important that their health is continually assessed to diagnose and treat injuries and the jockey allows the horse time to recover from the injury. The most common sites of injury include: forelegs, back and pelvis such as bowed tendon (tendonitis), strained suspensory ligaments, splints, osselets, sesamoid fractures, condylar fractures, knee fractures, bone chips, bucked skins and pin firing. It is vitally important that racehorses are allowed time to rest and heal after an injury. Training or racing a horse whilst injured can be detrimental.
Randox Equine Panel
Randox offer 10 scientifically proven assays for equine health which are made from the same high-quality material as our human assays, providing accurate and precise results. These assays have extensive measuring ranges for the accurate detection of disease or inflammation which are suitable for use with serum, plasma and whole blood. Instrument specific applications (ISA’s) are available for an extensive range of biochemistry analysers suitable for use with manual, semi-automated and fully automated analysers.
The Randox range of assays, suitable for equine use, cover a range of biomarkers:
Adiponectin is used to assess equine metabolic syndrome (EMS) which is characterised by obesity, regional adiposity, insulin resistance, and susceptibility to laminitis. Laminitis is one of the most common causes of lameness in horses. It is a painful and potentially crippling condition, which in severe cases usually results in the horse being humanely euthanised.
Aspartate Aminotransferase (AST) levels directly correlate with the severity of muscle inflammation or damage, or liver damage. The highest levels of AST will be seen around 24hours after muscle injury and persist for 2-3 weeks.
CK-NAC is a sensitive marker for the detection of musculoskeletal diseases; and is useful to assess the extent of severe muscle trauma, crush injuries, and burns and the likelihood of developing rhabdomyolysis.
Complement C4 – Biomarker for Systemic Lupus Erythematosus (SLE)
Systemic Lupus Erythematosus (SLE) is an autoimmune disorder associated with a deficiency in complement C4. Complement C4 is one of nine components of the complement system which is an integral part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the host, promote inflammation, and attack the cell membrane of pathogens.
Complement C4 is a vital component of two immunology pathways: Classical pathway and Mannrose Binding Lectin (MBL) pathway.
The classical pathway is triggered by antibody-antigen complexes which induces a conformational change in the C1 complex. The activated C1 complex cleaves the C4 component, resulting in a reactive C4b which covalently binds to proteins or polysaccharides at the surface in close proximity of the C1 component. The bound C4b complexes binds to the C2 component rendering C2 for proteolysis by C1.
The MBL pathway is activated through the binding of MBL to mannose residues on the pathogen surface. This in turn activates the MBL-associated serine proteases, MASP-1 and MASP-2, which activates the C4 and C2 components, to form the C3 convertase, C4b2a. The C4b2a complex splits C3 into two fragments which causes the release of vasoactive mediators such as histamine.
Complement C4 deficiency is commonly associated with systemic lupus erythematosus (SLE).
According to lupus.org, 16,000 new cases of lupus are reported each year. Approximately 1 in 250 people may end up developing SLE at some point with 90% of SLE patients being female aged between 15-44 years. The causes of SLE are unknown, but are believed to be linked to environmental, genetic, and hormonal factors. 1.5 million Americans are living with diagnosed lupus.
There are four forms of lupus:
- Systemic – accounts for approximately 70% of all lupus cases. In half of these cases, a major organ or tissue in the body, such as the heart, lungs, kidneys, or brain will be affected.
- Cutaneous lupus – accounts for approximately 10% of all lupus cases and only affects the skin.
- Drug-induced lupus accounts for approximately 10% of all lupus cases and is caused by high doses of certain medications.
- Neonatal lupus is a rare condition in which the mother’s antibodies affect the fetus. At birth, the baby may have a skin rash, liver problems, or low blood cell counts, but these symptoms typically disappear completely after six months with no lasting effects.
The Randox Complement C4 assay
The Randox Complement C4 assay is used for the quantitative in vitro determination of complement C4 concentration in serum. The Randox Complement C4 assay can be used as a biomarker in the diagnosis and monitoring of SLE. It is the cell-bound levels of processed complement activation products, especially E-C4d (erythrocyte-bound C4) that makes the complement C4 assay a biomarker for SLE.
Key Features of the Randox Complement C4 assay
Liquid ready-to-use reagents – The Randox reagent comes in a convenient liquid format requiring minimal preparation thus reducing the risk of errors.
Exceptional correlation with standard methods – The Randox methodology was compared against other commercially available methods and the Randox Complement C4 assay showed a correlation coefficient of r=0.98.
Wide measuring range – The healthy range for Complement C4 is 7 -49 mg/dl. The Randox Complement C4 assay can comfortably detect levels outside of the healthy range measuring between 2.90 – 152 mg/dl.
Excellent stability – Stable until expiry date when stored at +2 to +8°C.
Randox celebrate British Science Week 2018
The theme this year for British Science Week is exploration & discovery. Randox Laboratories was established in 1982 with the aim to revolutionise healthcare through continuously improving diagnostic solutions as diagnostics are vital to improving healthcare and disease diagnosis. To achieve this, 28% of the total annual revenue is reinvested in R&D.
Did you know?
The RX series have analyser placements in over 120 countries worldwide
5th largest manufacturer of clinical chemistry reagents in the world.
3rd largest manufacturer of QC and calibrators globally, supplying to 60,000 labs worldwide.
Largest international EQA scheme, with more than 45,000 lab participants in 133 countries.
Patient care is the primary focus of clinical chemistry testing and Randox has developed the RX series of clinical chemistry analysers for high quality semi-automated and fully automated testing. The RX series combines robust hardware and intuitive software with the world leading RX series test menu, including routine chemistries, specific proteins, lipids, therapeutic drugs, drugs of abuse, antioxidants and diabetes testing.
Renowned for quality and reliability, the RX series has one of the most extensive dedicated clinical chemistry test menus on the market guaranteeing real cost savings through consolidation of routine and specialised tests onto a single platform. This extensive dedicated test menu of high quality reagents guarantees excellence in patient care ensuring unrivalled precision and accuracy reducing costly test re-runs or misdiagnosis and offering complete confidence in results.
The RX series offers both semi-automated and fully automated clinical chemistry analysers to suit your laboratory needs. Choose from the RX misano, RX monaco, RX daytona+, RX imola and RX modena to start your journey with the RX series today.
The market-leading reagents portfolio from Randox is internationally recognised as being of the highest quality, offering rapid and reliable results. With 118 assays, covering over 100 disease markers, Randox offers the most comprehensive product portfolio in the diagnostic market incorporating antioxidants, cardiology, diabetes, drugs of abuse, hepatic function, lipids, renal function, specific proteins, therapeutic drug monitoring and veterinary testing. Randox assays are available in a wide range of formats and methods providing greater flexibility and choice for your laboratory. In addition to flexible pack sizes, a comprehensive list of 13,000 applications for 195 clinical chemistry analysers can be provided as dedicated reagent packs (Easy Read & Easy Fit Reagents).
Through continued exploration to expand the clinical test panels, Randox discovered numerous high performing and unique tests. These tests are either unique to Randox or offer a superior methodology for more accurate results. Such tests include:
– Adiponectin is a protein hormone secreted by adipocytes which has an important role in a number of metabolic processes. Adiponectin is a diabetes biomarker as adiponectin levels are inversely correlated with abdominal visceral fat (AVF) levels, which has proven to be a strong predictor of several pathologies including metabolic syndrome, type 2 diabetes mellitus (T2DM), some cancers and cardiovascular disease (CVD).
– Cystatin C is a small cysteine proteinase inhibitor that is produced at a constant rate by all nucleated cells. Cystatin C is a more sensitive marker of renal function than creatinine as up to 50% of renal function can be lost before significant creatinine levels become detectable. Cystatin C is also useful in patients where creatinine measurements are inconclusive or unreliable, such as patients who are obese, malnourished, have liver cirrhosis or reduced muscle mass.
– 5th Generation Bile Acids is a highly sensitive marker of hepatic function, enabling the early detection of liver disease. The Randox 5th Generation Bile Acids assay utilises an advanced enzyme cycling method which displays outstanding sensitivity and precision when compared to traditional enzymatic based tests.
The Randox High Performance and Unique Tests brochure can be downloaded here for further information.
As the aim of British Science Week 2018 is to inspire innovation and celebrate science, Randox Quality Control are celebrating the fact that we have evolved into one of the principal manufacturers of quality controls and calibrators in the world. With approximately 70% of clinical decisions based on laboratory test results, it is clear to see the significant role laboratory testing plays. Our extensive range of Acusera Controls help labs to find and correct flaws in their analytical processes before potentially incorrect patient results are released, ultimately helping to improve health worldwide.
With more than 390 analytes available across the range, labs can significantly reduce costs without compromising on quality. We specialise in consolidation, our range of multi-analyte controls is designed to cover your test menu, ultimately reducing costs, preparation and storage space for any lab.
Manufactured independently, our third-party range of controls delivers unbiased performance assessment with any instrument or method, furthermore our commutable materials are designed to mimic the patient sample and ensures accurate and reliable test results. Designed to complement our range of third party controls the Acusera 24•7 software is the only peer group program to offer automatic calculation of measurement uncertainty helping laboratories to meet ISO 15189 requirements. Peer group statistics are also uniquely updated live, in real-time giving you access to the most up-to-date information possible enabling rapid and effective troubleshooting.
As the largest EQA scheme in the world, RIQAS (Randox International Quality Assessment Scheme) is used by more than 45,000 laboratory participants in 133 countries worldwide. Comprising 33 programmes a wide range of clinical testing is covered. Each RIQAS programme delivers high quality samples spanning clinically relevant levels to allow identification of concentration related biases; our frequent, user-friendly reporting enables early identification of system errors and our report turnaround time of less than 72 hours from the submission deadline, ensures corrective action can be implemented earlier, reducing costly errors with patient results.
Diagnostics is the key enabler to improve healthcare, patient outcomes and reduce the burden on healthcare; 80% of all medical decisions are based on diagnostic tests. In 1982, we had meagre resources, but we felt we could develop and manufacture world class diagnostic tests. Through continuously improving diagnostic solutions through exploration and discovery, Randox are a world leading manufacturer of diagnostic solutions.