Could there be 5 types of diabetes?

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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.

 

References

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.

If you are a clinician, dietitian or laboratory who are interested in running diabetes assays, Randox offer a wide range of high-quality routine and niche assays including: fructosamine, glucose, HbA1c for diagnosing and monitoring diabetes, albumin, beta-2 microglobulin, creatinine, cystatin c, NEFA, microalbumin, and d-3-hydroxybutyrate to monitor associated complications, and adiponectin  as a biomarker for diabetes risk assessment.  These assays can be run on most automated biochemistry analysers.

Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.

For more information, visit: https://www.randox.com/diabetes-reagents or email: reagents@randox.com 


Randox Reagents are Supporting World Kidney Day 2018

On 8th March 2018, Randox Reagents are supporting World Kidney Day!  World Kidney Day is an annual campaign and partnership to raise awareness of the importance of our kidneys to our overall health and to reduce the frequency and impact of kidney disease and its associated health problems worldwide.

 

This year, the World Kidney Day theme is: “Kidney Disease and Women’s Health: Include, Value, Empower”.  Chronic kidney disease affects approximately 195 million women worldwide and it is currently the 8th leading cause of death in women, with close to 600,000 deaths per year.

 

Chronic kidney disease in women has increased over the years.  Women over the age of 50 and African American women have seen the highest rise of kidney failure.  This has been attributed to obesity, diabetes and high blood pressure.  It is important that women are screened for renal impairment as although treatment of kidney disease in men and women are the same, the complications associated with renal impairment in women is greater than in men.  The complications women are faced with due to renal impairment include: irregular periods, diminished sex drive and difficulties conceiving.  Whilst it is difficult for a woman with renal impairment to conceive, it is not impossible, however, 50% of babies born to women on dialysis survived with most being born prematurely due to high blood pressure.  There are several measures that women can take to reduce their likelihood of developing renal impairment or manage their symptoms including; lifestyle changes, medication to control associated problems, dialysis and kidney transplant.

 

The standard marker for renal functional is creatinine as creatinine clearance gives a measure of the glomerular filtration rate (GFR), however, creatinine levels are unreliable in individuals who are obese, malnourished, have liver cirrhosis or reduced muscle mass.  Due to this, Randox developed an automated test for Cystatin C, a superior marker of kidney dysfunction.

 

The Randox Cystatin C assay

Cystatin C is a small (13kDa) cysteine proteinase inhibitor that is produced at a constant rate by all nucleated cells.  The small molecular weight of cystatin C allows it to be completely removed and broken down by the kidneys.  Therefore, levels remain steady if the kidneys are working efficiently and the Glomerular Filtration Rate (GFR) is normal.

There are several studies that have documented the superiority of cystatin C compared to creatinine as a marker of GFR function.  Unlike creatinine, cystatin C does not have a ‘blind area’ meaning it is extremely sensitive to very small changes in GFR and therefore capable of detecting early reductions in GFR.  Up to 50% of renal function can be lost before significant creatinine levels are detected.  GFR estimates based on cystatin C are less influenced by diet or muscle mass compared to GFR estimates based on creatinine, therefore, Cystatin C is also beneficial if the patient is overweight, elderly or has a lot of muscle mass. Cystatin C is also beneficial if previous kidney function tests were inconclusive.

World Kidney Day and Randox are working towards improving healthcare globally.  With continuous investment into R&D, Randox are striving to develop the earliest biomarker for renal function to prevent serious complications.

 

For more information, download our High Performance & Unique Tests Brochure or email reagents@randox.com.

Cystatin C

 

 

For health professionals

If you are a clinician or laboratory who are interested in running renal function assays, Randox offer a wide range of high-quality routine and niche assays including:  Albumin, Ammonia, β2- Microglobulin, Calcium, Chloride, Creatinine Enzymatic and Jaffe, Cystatin C, Glucose, HbA1c, IgG, LDH, Magnesium, Microalbumin, Phosphorus (Inorganic), Potassium, Sodium, Urea, Uric Acid, and Urinary Protein. These can be run on most automated biochemistry analysers.

For more information, download our High Performance & Unique Tests Brochure or email reagents@randox.com.


Acetaminophen-Induced Acute Kidney Failure

Acetaminophen is a commonly used medicine for pain-relief.  During cold and flu season, it is common to resort to pain-relief medicines to relieve headaches, and ache and pain symptoms associated with a cold or flu as there is no cure.  However, the therapeutic range for acetaminophen is 10-30 mg/l, which is small and very easy to go over.  During cold and flu season, it is important to monitor the amount of paracetamol entering your body as acetaminophen is more dangerous than suspected.  At therapeutic levels, acetaminophen does not produce any adverse effects, however, long-term treatment, prolonged use, and taking a few more than the recommended dose can be severely damaging and fatal.  Accidental acetaminophen overdose took the lives of 1,500 people in the U.S between 2001 and 2010.  The Randox Acetaminophen assay is used to determine the concentration levels of acetaminophen in the blood to determine if an overdose has taken place.

 

It is commonly recognised that acetaminophen overdose causes hepatotoxicity, but it is less commonly recognised that it can also cause nephrotoxicity in less than 2% of patients.  Nephrotoxicity is toxicity of the kidneys and is often associated with a reduced amount of glutathione which is important for normal cellular metabolism in the kidneys.  The Randox Glutathione Reductase assay is required for the regeneration of reduced glutathione.  Glutathione is often discussed in association with the Randox Glutathione Peroxidase, which requires reduced glutathione for activation.  Both Glutathione reagents are unique to Randox.

 

Acute renal failure due to acetaminophen manifests as acute tubular necrosis, which can occur alone or in combination with hepatic necrosis.  Nephrotoxicity can also occur when the therapeutic levels of acetaminophen are not exceeded.  This most commonly occurs when acetaminophen is taken in combination with alcohol.  Upon testing acetaminophen levels and the results fall within the therapeutic range, the Randox Ethanol assay can test alcohol levels to determine if a combination of alcohol and acetaminophen caused nephrotoxicity.  Renal impairment may be more common than previously suspected as acute renal failure occurs in 10-40% of patients with severe hepatic necrosis.  Upon testing acetaminophen to determine toxicity, Randox also offer the following renal tests to test for nephrotoxicity:

 

For more information visit: https://www.randox.com/acetaminophen

To request an application for your specific analyser, contact reagents@randox.com


Randox Reagents celebrate World Kidney Day 2017

On 9 March 2017, Randox Reagents are celebrating World Kidney Day!  World Kidney Day is a global campaign aimed at raising awareness of the importance of our kidneys to our overall health. It aims to reduce the frequency and impact of kidney disease and its associated health problems worldwide.

This year, the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviours an affordable option.

With this in mind, throughout the week we have been sharing on social media some interesting facts on diagnostic tests which can help aid an early risk assessment of kidney disease in obese patients, allowing preventative action to be taken before any serious damage occurs.  The tests of focus this week included cystatin C, adiponectin and microalbumin

Cystatin C

The creatinine test is routinely run for patients who are suspected for deteriorating kidney function, however this test has limitations.  Cystatin C is an alternative test, and is particularly useful in patients where creatinine measurements are not suitable e.g. individuals who are obese, malnourished, have liver cirrhosis or reduced muscle mass. Importantly, unlike creatinine, cystatin C does not have a ‘blind area’ – up to 50% of kidney function can be lost before significant creatinine elevation occurs. Cystatin C is extremely sensitive to very small changes in kidney function and is therefore capable of detecting early stage kidney dysfunction.  The cystatin C test therefore allows preventative measures to be taken much earlier and before significant kidney function decline.

Adiponectin

There is substantial evidence that excess visceral fat is the main driving force for almost all of the disorders associated with the metabolic syndrome, including CKD.1,2 The adiponectin test from Randox can accurately assess levels of abdominal visceral fat, independent of age, race or fitness level.3,4  Assessing adiponectin, and therefore visceral fat levels, can help assess risk of CKD, as well as a range of other illnesses such as pre-diabetes, CVD and various cancers.

 

Microalbumin

The microalbumin test detects very low levels of a blood protein called albumin, in urine. The detection of albumin in urine can be an indicator of kidney injury and can result in irreversible damage if left untreated. Low albumin concentrations in the urine are the earliest marker of kidney damage and therefore enable preventative measures to be taken.  Microalbumin testing can identify individuals with diabetic nephropathy approximately 5-10 years earlier than proteinuria tests helping reduce the frequency of end stage renal disease.

Both World Kidney Day and Randox are working towards improving healthcare worldwide. With continuous investment in R&D, Randox are helping with the risk assessment and earliest detection of renal function problems. By assessing one’s risk of kidney problems (with the adiponectin test), it can give patients (obese and other) the tools to prevent kidney problems further on down the line.  With early diagnosis (through the cystatin C and microalbumin tests) it will be possible to keep kidney problems from getting worse, therefore lowering the number of those diagnosed with CKD worldwide.

For health professionals

If you are a clinician or lab interested in running renal function assays, Randox offers a large range of high quality routine and niche assays including:  Cystatin C, Creatinine Enzymatic and Jaffe, Microalbumin, Urinary Protein, Urea, Sodium, Potassium, Albumin, Ammonia, β2- Microglobulin, Calcium, Chloride, Glucose, HbA1c, IgG, LDH, Magnesium, Phosphorus (Inorganic), and Uric Acid. These can be run on most automated biochemistry analysers.

For more information, download our Diabetes Brochure or email reagents@randox.com.

References

  1. Hall JE, Henegar JR, Dwyer TM, et al. Is obesity a major cause of chronic renal disease?Adv Ren Replace Ther. 2004;11(1):41–54. [PubMed]
  2. Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update.Physiol Rev. 2013;93(1):359–404. [PubMed]
  3. Matsuzawa, Y. The role of fat topology in the risk of disease.  Int J Obes.  2008;32:s83-s92.
  4. Frederiksen, L., Nielsen, T. L., Wraae, K., Hagen, C., Frystyk, J., Flyvbjerg, A., Brixen, K. and Andersen, M. Subcutaneous Rather than Visceral Adipose Tissue Is Associated with Adiponectin Levels and Insulin Resistance in Young Men.  JCEM, (2009) 94 (10): 4010-4015.

 

Further reading:


3 million people in England could have been spared chronic kidney disease – as health watchdog calls for changes to testing

  • Precision test detects minute deterioration in kidney function
  • Identifies patients at early stages – missed by current testing
  • NICE says new test regime could cut the number of patients on medication and dialysis by up to 20%
  • Chronic kidney disease affects older people and more common in women
  •  Unchecked, CKD can eventually cause kidney failure and death
  • CKD linked to diabetes, hypertension and cardiovascular disease

Millions of people in the UK are needlessly suffering from advanced kidney disease, because of a ‘blind spot’ in current testing methods. The traditional test used by the NHS to identify kidney dysfunction, measures the level of a waste product (Creatinine), which is only raised when up to 60% of the kidney has already been damaged. This damage is irreversible, with dialysis or transplant the only available therapies.

As kidney disease progresses, waste builds up in the blood which can have a significant impact on other key areas of the body; impairing heart health, weakening bones, reducing immune response and damaging the central nervous system. If left unchecked, CKD can cause kidney failure and death.

With early detection, the progression of CKD can be prevented; in response to this the National Institute for Health and Care Excellence, has drafted new guidance for doctors to improve diagnosis and identify kidney dysfunction in the earliest stages. The health watchdog makes it clear that a highly sensitive test for the biomarker Cystatin C, should be used alongside the traditional creatinine test, for more accurate and earlier identification of kidney function deterioration.

Cystatin C is a protein produced by the body at a constant rate, its small molecular weight allows it to be completely broken down and removed by the kidneys; levels therefore, remain steady if the kidneys are working efficiently and the glomerular filtration rate (GFR) is normal. If kidney function deteriorates, Cystatin C concentrations rise.

Testing for cystatin c means doctors can pick up on even the smallest changes in GFR, identifying a drop in kidney function at the earliest opportunity. Once a problem has been spotted early it can be managed through medication and/or changes to diet and lifestyle, preventing chronic kidney disease from occurring.

Around 2 million adults in England have CKD – but as it is largely asymptomatic and often undiagnosed, it is thought a further 1 million could also be suffering from the advanced stages of the disease. Dr Gilbert Wieringa, Consultant Biochemist at Bolton NHS Foundation Trust, a keen advocate of the test commented:

“I welcome the fact that NICE now recognises Cystatin C as a key biomarker in the differential diagnosis of CKD. The ready availability of this blood test ensures the right treatment can be started for the right patient in the right time in turn helping to prevent or delay progression of CKD, reducing or delaying complications, and reducing the risk of cardiovascular disease. It provides a key example where investment in a diagnostic test helps reduce far greater cost burdens of managing secondary complications further down the line”

NICE says that while using the cystatin c test will increase the cost of diagnosis “accuracy is expected to improve and fewer people are expected to require treatment and monitoring”.

Dr Peter FitzGerald, MD at UK Biotech firm Randox, which has created a cystatin C test for use in every standard hospital lab in the UK, believes the new diagnostic method could have a significant impact on the financial burden of CKD on the NHS:

“CKD is closely linked with diabetes, obesity, stoke and cardio vascular disease – as we see these conditions increase across the UK, so too will the prevalence of CKD, but if we can catch kidney function damage early, we can prevent CKD and prevent the need for expensive medical interventions such as dialysis, the cost of which per patient, per year is around £31,000. Needless to say, it also comes at considerable personal expense, but this does not have to be the way.”

NICE estimates that up to 20% of the current CKD population may not have needed medication, if the new testing method was introduced and says “savings are expected at a local level as a result of this change.”


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