Diabetes: The Role of Fructosamine
Diabetes Week is an annual week to raise awareness of diabetes. This year, the aim is to increase the public’s understanding of diabetes 1. Diabetes mellitus (DM) is a global epidemic, increasing at an alarming rate and burdening healthcare systems 2. DM is a life-long condition characterised by the body’s inability to produce / respond to insulin resulting in the abnormal metabolism of carbohydrates and elevated blood glucose levels.
Whilst it is important to increase the public’s understanding of DM, it is imperative that clinicians and physicians are aware of the different in vitro diagnostic tests to diagnose and monitor DM. Not only is this vital, but is also important that clinicians and physicians also understand the different methodologies available when choosing the diagnostic test.
It has been highlighted in numerous clinical studies that diabetic complications may be reduced through the long-term monitoring and tight control of blood glucose levels. Both fasting plasma glucose (FPG) and glycated haemoglobin A1c (HbA1c) tests are universally accepted as reliable measurements of diabetic control. However, studies have emerged highlighting the role of fructosamine in diabetes monitoring. Whilst HbA1c provides an index of glycaemia over 2 to 3 months, fructosamine provides this index over the course of 2 to 3 weeks, enabling closer monitoring of diabetic control 1.
Drawbacks of Traditional Diabetes Tests
The FPG test measures the level of blood sugars which is used to diagnose and monitor diabetes based on insulin function. The main drawback of this test is that a hormone called glucagon, produced in the pancreas, is triggered during prolonged fasting, signalling the liver to release glucose into the bloodstream. In diabetic conditions, either the body is unable to generate enough insulin or cannot appropriately respond to insulin. Consequently, FPG levels remain high 4.
In the 1980’s, HbA1c was incorporated into clinical practice as HbA1c levels correlated well with glycaemic control over a 2 to 3-month period. The main drawback of this test is that any condition that reduces the survival rate of erythrocytes such as haemolytic anaemia will falsely lower the HbA1c test results, regardless of the assay method utilised 5.
In a diabetic patient where blood glucose levels are abnormally elevated, the concentration levels of fructosamine also increase as fructosamine is formed by a non-enzymatic Maillard reaction between glucose and amino acid residues of proteins. During this glycation process, an intermediate labile Schiff base is produced which is converted to a more stable ketoamine (fructosamine) via an Amadori rearrangement 2.
Fructosamine has been identified as an early indicator of diabetic control compared to other markers such as HbA1c. Red blood cells live for approximately 120 days, HbA1c represents the average blood glucose levels for the previous 2 to 3 months. Conversely fructosamine has a shorter lifespan, about 14 to 21 days, reflecting average blood glucose levels from the previous 2 to 3 weeks. Due to the shorter time span of fructosamine, it is also used to evaluate the effectiveness of medication changes and to monitor the treatment of gestational diabetes. The test is also particularly useful in situations where HbA1c cannot be reliably measured e.g. haemolytic anaemia, thalassemia or with genetic haemoglobin variants 5.
Fructosamine Assay Methodology
The most commonly utilised method for fructosamine testing is the colorimetric method. Whilst widely available, automated and inexpensive, the main drawback is the lack of standardisation across the different fructosamine assays 4.
Randox, on the other hand, utilise an enzymatic method, offering improved specificity and reliability compared to conventional NBT-based methods. The Randox enzymatic method does not suffer from non-specific interferences unlike existing methods which can also be time consuming and difficult to automate.
The Randox fructosamine assay is also standardised to the highest level as the Randox fructosamine calibrator and control is assigned relative to human serum glycated with 14C-glucose, which directly reflects the nature of the patient sample.
With an excellent stability of 28 days on-board the analyser, the Randox fructosamine assay is developed in a liquid ready-to-use format for convenience and ease-of-use.
Randox offer fully automated applications detailing instrument-specific settings for the convenient use of the Randox fructosamine assay on a wide range of clinical chemistry analysers.
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Reagents Resource Hub
 Diabetes UK. Diabetes Week. [Online] 2019. [Cited: May 31, 2019.] https://www.diabetes.org.uk/get_involved/diabetes-week.
 Gounden, Verena and Jialal, Ishwarlal. Fructosamine. [Online] January 23, 2019. [Cited: April 11, 2019.] https://www.ncbi.nlm.nih.gov/books/NBK470185/.
 World Health Organization (WHO). Diabetes. [Online] October 30, 2018. [Cited: May 2, 2019.] https://www.who.int/news-room/fact-sheets/detail/diabetes.
 Manzella, Debra. The Fasting Plasma Glucose Test. very well health. [Online] November 16, 2018. [Cited: April 11, 2019.] https://www.verywellhealth.com/understanding-the-fasting-plasma-glucose-test-1087680.
 BMJ. Using haemoglobin A1c to diagnose type 2 diabetes or to identify people at high risk of diabetes. [Online] 2014. [Cited: April 11, 2019.] https://www.bmj.com/content/348/bmj.g2867/rr/695927.
Approximately 400,000 people in the UK are living with type 1 diabetes, with over 29,000 being children and young people . Type 1 diabetes affects 96% of all children with diabetes in England and Wales, with incidences increasing by approximately 4% each year.
Globally, the UK has the fifth highest rate of type 1 diabetes diagnosis in children (aged up to 14) with 85% of these children having no family history of the condition. Whilst the condition isn’t fatal and can be managed, it cannot be cured. Type 1 diabetes increases the risk of developing other health problems such as heart disease, stroke, foot and circulation problems, sight problems including blindness, nerve damage and kidney problems. However, many of these related conditions are preventable and it is recommended to stabilise blood sugar levels, attend diabetes appointments regularly and complete a diabetes course to educate patients and family members and prevent the risk of further help complications.
Diabetes in children
Children under five are at the highest risk of developing diabetic ketoacidosis due to a late diagnosis and it is also thought to be due to of lack of public knowledge of the signs and symptoms attributed to type 1 diabetes. Such symptoms include:
- Frequent urination as the kidneys are trying to expel excess sugar in the blood, resulting in dehydration which leads to extreme thirst.
- Increased hunger or unexpected weight loss because the body is unable to attain enough energy from food
- Slow healing cuts as high blood sugar levels can affect blood flow which can cause nerve damage.
- Fatigue as the body is unable to convert sugar into energy
- Irritable behaviour combined with other symptoms can be a means of concern
Diabetes and the NHS
Diabetes costs the NHS approximately £9.8 billion per year, an estimate of 10% of total expenditures. Hospital admissions of children and young people with diabetes presents a considerable burden on themselves, their families and the NHS. It is estimated that approximately 80% of these cases are potentially avoidable.
A report produced by the National Paediatric Diabetes Audit found that although the numbers of admissions didn’t significantly differ year to year, it highlighted differences in terms of socio-economic risk factors:
- Living in a deprived area increases the risk of hospital admissions which can be attributed to lack of education in the community about diabetic symptoms and the management of diabetes.
- Children below 5 years of age have a 35% increased risk of hospitalisation compared to those aged 5-9
- Females have a 33% increased risk of developing type 1 diabetes compared to males.
- Children with poor diabetes control have a twelve-fold increased risk of hospital admission
- Insulin pump users have a 27% increased risk of hospital admission compared to those who use insulin injections.
Figure A. Number of preventable paediatric diabetes admissions 
There are campaigns in place to aid in the early diagnosis of type 1 diabetes which mainly focus on raising awareness of the signs and symptoms of diabetes. On this World Diabetes Day, it is important to know that it is not just simply the responsibility of the diabetic patient to prevent admission but the main responsibility lies with the diabetic teams that inform the families with children who are diagnosed with type 1 diabetes.
Paediatric diabetes teams should ensure that the families and the children receive structured education for self-management when diagnosed and throughout the illness. In doing so, the diabetic teams should implement blood ketone testing from diagnosis and utilise the nationally agreed hypoglycaemia management guidelines. It is also important that diabetic teams are fully aware of the patient characteristics associated with a greater risk of admission and that they use this knowledge to develop anti-admission strategies specifically tailored to the needs of each individual group.
Primary care practitioners should seek access to a specialist diabetic team who they can refer to when deciding if a patient requires admission to hospital. Furthermore, they should access blood glucose and ketone testing to identify patients at risk of diabetic ketoacidosis that require hospital admission.
How Randox can Help
Randox offer a range of assays to diagnosis and monitor diabetes and to monitor associated complications. Some of these tests are unique to Randox, including:
The Randox fructosamine assay employs the enzymatic method which offers improved specificity and reliability compared to conventional NBT-based methods. The Randox enzymatic method does not suffer from non-specific interferences unlike other commercially available fructosamine assays.
The Randox D-3-Hydroxybutyrate (Ranbut) assay detects the most abundant and sensitive ketone in the body, D-3-Hydroxybutyrate. The Randox Ranbut assay is used for the diagnosis of ketosis, more specifically diabetic ketoacidosis. Other commercially available tests, such as the nitroprusside method, are less sensitive as they only detect acetone and acetoacetate, not D-3-Hydroxybutyrate.
The Randox adiponectin assay is a biomarker in diabetes testing as adiponectin is a protein hormone responsible for regulating the metabolism of lipids and glucose and influences the body’s response to insulin. Adiponectin levels inversely correlates with abdominal visceral fat levels.
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 National Paediatric Diabetes Audit and Royal College of Paediatrics and Child Health, National Paediatric Diabetes Audit Report 2012-15: Part 2, 2017
 NHS, “Avoiding Complications” – Type 1 Diabetes, Available at: https://www.nhs.uk/conditions/type-1-diabetes/avoiding-complications/ [Accessed on 24th October 2018].
 “Potentially Preventable Pediatric Hospital Inpatient Stays for Asthma and Diabetes, 2003-2012”, www.hcup-us.ahrq.gov, 2015. [Online] Available: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb192-Pediatric-Preventable-Hospitalizations-Asthma-Diabetes.jsp [Accessed 08-Nov-18]
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.
More and more women in the United States are waiting until they’re older to start having children.
The number of births to women aged 45–49 rose 14% in 2013 from 2012, according to the Centers for Disease Control and Prevention’s National Vital Statistics Report. With this comes the responsibility by clinicians and laboratories to better assess those at risk of gestational diabetes and to aid better control of the condition for those who already have it. Quick and precise detection of risk of gestational diabetes and associated complications by clinical labs will provide women with the autonomy to take control of their maternal health.
Innovations in maternal health testing have meant that analysis such as adiponectin and enzymatic fructosamine are now available in automated biochemistry formats and with more accurate methodologies; allowing laboratories to assess gestational diabetes risk, and evaluate control of the condition with ease, speed and accuracy. Testing of such analytes have historically been non-routine and not easily accessible for clinical laboratories, and now with little adjustment within the laboratory, these can be added to the test menu allowing for detailed patient testing profiles.
Current innovations in the area of gestational diabetes testing will ultimately secure the health, both during and post-pregnancy, of mother and baby.