Differentiating Type 1 and Type 2 Diabetes Mellitus

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Differentiating Type 1 and Type 2 Diabetes Mellitus

An estimated 422 million people across the world are living with diabetes1. Diabetes Mellitus (DM) encompasses a collection of chronic diseases characterised by absent or ineffective insulin activity. Insulin is a hormone produced by the pancreas responsible for a host of essential physiological processes related to glucose metabolism and protein synthesis.

There are two main forms of DM, named type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) which result from different mechanisms and more importantly, require different therapeutic approaches. It is estimated that up to 40% of those diagnosed with T1DM after the age of 30 may have been misdiagnosed with T2DM2. This misdiagnosis of T1DM as T2DM will result in poor glycaemic control, frequent healthcare contact for increased treatment, inappropriate insulin regimes and risk of life-threatening ketoacidosis.

In this article, we’ll look at the similarities and differences between these two forms of DM and investigate the mechanisms by which these common diseases arise.

Insulin Pathway

The normal insulin signalling pathway, shown below, is responsible for the processing and transport of glucose in the body. Briefly, insulin binds to the insulin receptor and activates PI3K and, subsequently, serine-threonine kinase (AKT). AKT is responsible for the phosphorylation of glycogen synthase kinase 3-β (GSK-3β), inhibiting its activity and promoting the synthesis of glycogen leading to a reduction in blood glucose concentration.  Failing to inhibit GSK-3β will result in hyperglycaemia and eventually T2DM.

Type 1 Diabetes Mellitus

T1DM is most commonly diagnosed at a young age. This form of DM is the result of an autoimmune reaction to proteins produced by the pancreas which results in a lack of insulin secretion. The antibodies responsible for this autoimmunity are detailed in the table below:

A key factor in T1DM pathogenesis is changes in the T cell-mediated immunoregulation, notably in the CD4+ T cell compartment. The activation of the CD4+ T cells is responsible for inflammation of the pancreatic cells which produce insulin, known as insulitis.

Changes in the expression of IL-1 and TNFα cause structural alterations in pancreatic β-cells which result in the suppression of insulin secretion.  This insulin deficiency has subsequent effects on glucose metabolism and protein synthesis.

T1DM causes an increase in hepatic glucose levels when gluconeogenesis converts glycogen to glucose. A lack of insulin means the subsequent hepatic uptake of this glucose does not occur.

Insulin is also responsible for regulating the synthesis of many proteins. This regulation can be positive or negative but ultimately results in an increase in protein synthesis and a decrease in protein degradation. Therefore, when hypoinsulinemia occurs, decreasing insulin concentration in the blood, protein catabolism is increased leading to increased plasma amino acid concentration.

Type 2 Diabetes Mellitus

The pathogenesis of T2DM, detailed in the diagram below, is multi-factorial. It arises from a combination of genetic and environmental factors which affect insulin activity.

In T2DM, the regulatory mechanisms related to glucose metabolism fail resulting in impaired insulin activity or insulin resistance.

Mutations in genes involved in insulin production can cause the secretion of abnormal insulin molecules, known as insulinopathies. Insulinopathies are unable to effectively metabolise glucose which results in the accumulation of this sugar. Additionally, obesity is considered to be a causal factor in the development of T2DM.

Unlike those with T1DM, patients with T2DM can maintain circulating insulin levels. T2DM is characterised by glucose intolerance, impaired glucose tolerance, diabetes with minimal fasting hyperglycaemia, and DM in association with overt fasting hyperglycaemia.

Individuals with impaired glucose tolerance have hyperglycaemia despite preserving high levels of plasma insulin. These levels of insulin decline from impaired glucose tolerance to DM. It is insulin resistance is considered the primary cause of T2DM.

Misdiagnosis

The misdiagnosis of these types of DM is common, due to similar symptoms. The simplest differentiating factor is when these symptoms manifest. T1DM is an autoimmune disorder and therefore, symptoms generally occur much earlier in one’s life. T2DM is typically diagnosed in later life. The common symptoms of DM are:

  • Frequent urination, particularly throughout the night.
  • Polydipsia (excessive thirst)
  • Polyphagia (excessive hunger)
  • Lethargy
  • Sudden weight loss
  • Genital itching or thrush
  • Blurred vision

The misdiagnosis of T2DM as T1DM results in unnecessary initial insulin therapy, higher drug and monitoring costs and often, an increase in the number and severity of symptoms. Conversely, the incorrect classification of T1DM as T2DM causes poor glycaemic control, frequent visits to healthcare services for treatment, inappropriate insulin regimes and risk of Diabetic Ketoacidosis.

Diabetic Ketoacidosis (DKA)

DKA is a potentially life-threatening condition caused by an accumulation of ketones in the body due to insulin deficiency, which is common in patients with T1DM, however, an increasing number of cases have been reported in patients with T2DM. Diagnosis of DKA consists of a high anion gap metabolic acidosis, ketone bodies present in serum and/or urine, and high blood glucose concentration. The symptoms of DKA include:

  • Polyuria (excessive urination) and polydipsia (thirst)
  • Weight loss
  • Fatigue
  • Dyspnoea (shortness of breath)
  • Vomiting
  • Fever
  • Abdominal pain
  • Polyphagia (excess hunger)
  • Fruity-smelling breath caused by acetone accumulation.

Randox Type 1 Diabetes Mellitus Genetic Risk Array

T1DM is largely genetic and is associated with over 50 distinct genetic signatures, many of which are single nucleotide polymorphisms (SNPs). This is of great advantage in testing as unlike traditional biomarkers, genetic markers don’t change throughout one’s life, providing a robust method for diagnosis and risk stratification. Genetic data gathered can then be used to develop a genetic risk score, allowing an individual’s probability of developing the disease to be quantified.

Using this principle, together with our patented Biochip array technology, Randox have developed a T1DM GRS array. Using a combination of 10 SNPs from the HLA region and the non-HLA region commonly detected in T1DM patients, and a selection of other risk factors and biomarkers, this molecular array can accurately discriminate between T1DM and T2DM.

Conclusions

Misdiagnosis of DM can have life-threatening consequences. Both types of DM are very common and distinguishing between T1DM and T2DM is crucial.

T1DM is an autoimmune disorder with a lack of insulin secretion, while T2DM is primarily due to insulin resistance. Understanding their mechanisms is vital for accurate diagnosis and treatment. Genetic testing, like the Randox Type 1 Diabetes Mellitus Genetic Risk Array, can differentiate between T1DM and T2DM by analysing genetic markers and providing personalized treatment insights.

Accurate diabetes diagnosis is crucial for proper management, prevention of complications, and improving the lives of millions. Together, we can make a difference in the lives of those affected by diabetes!

If you’d like to learn more about the different types of DM, including the pathogenesis, pathophysiology, associated risk factors, and more, please take a look at our educational guide Diabetes Solutions.

Alternatively, feel free to reach out to our marketing team at marketing@randox.com who will be happy to help you with any queries you may have.

References

  1. World Health Organization. Diabetes. World Health Organisation. Published April 5, 2023. Accessed April 25, 2023. https://www.who.int/news-room/fact-sheets/detail/diabetes
  2. The Misdiagnosis of type 1 and type 2 diabetes in adults. The Lancet Regional Health. 2023;29:100661-100661. doi:https://doi.org/10.1016/j.lanepe.2023.100661

D-3-Hydroxybutyrate & Diabetic Ketoacidosis

Diabetic Ketoacidosis is characterised by an accumulation of ketone bodies in response to insulin deficiency, most commonly occurring in T1DM patients, but is becoming increasingly prevalent among sufferers of T2DM.

Diabetic ketoacidosis is associated with symptoms such as polyuria, polydipsia, fever, vomiting, abdominal pain and fatigue with the most severe cases resulting in disastrous consequences such as cerebral oedema and death.

D-3-Hydroxybutyrate is considered to be the predominant ketone bodies associated with diabetic ketoacidosis and novel methods of detection utilise this biomarker to provide robust and accurate quantification of ketone bodies and aid in confident diagnosis of diabetic ketoacidosis.

This guide discusses the physiological and pathological processes associated with diabetic ketoacidosis and the relevant biomarkers, the complications associated with this condition and classic and novel detection methods.

To download this guide, simply click the image at the top of this post!
For more information on this assay visit https://www.randox.com/d-3-hydroxybutyrate-ranbut/
To read about some of our other superior performance reagents visit https://www.randox.com/superior-performance-and-unique-
Or, to view our wide range of diagnostic solutions visit https://www.randox.com/

 

Randox Reagents H-FABP & AKI

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

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

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 reagents@randox.com.

diagnostic tests

What is Visceral Fat?

Visceral fat (or abdominal fat) is body fat which is stored within the abdominal cavity. It wraps around your vital organs including the liver, pancreas and intestines, and as a result can have a negative impact on your health. In fact, visceral fat has been linked to increased risk of health problems such as type 2 diabetes, heart disease and some cancers.

It is important to distinguish the difference between subcutaneous fat and visceral fat…

Subcutaneous fat is the fat we store under our skin. It is the tissue that we can feel when we pinch ourselves, and contains blood vessels in addition to fatty tissues. Visceral fat, on the other hand, cannot be felt in such a way as it is the extra fat stored around our organs. It is the most dangerous type of fat as it much harder to identify.

No matter what your shape or size, you may be carrying excess visceral fat!

Regardless of shape or size an individual can be carrying excess visceral fat. This means that whether your doctor tells you that you’re underweight, overweight, obese or of a healthy weight, you may be carrying excess visceral fat within your abdominal cavity.

That is why BMI is an inaccurate measurement of health…

Body Mass Index (BMI) is used by many as an indicator of health. It involves comparing your weight in relation to your height to give an indication of your weight status i.e. whether you are categorised as underweight, overweight, healthy or obese. It doesn’t take into account muscle mass, age, sex, ethnicity, general level of fitness or visceral fat. Therefore, even if you have a ‘healthy’ BMI you may still be carrying excessive visceral fat, and could still be at risk of the health complications associated with it.

As a result, relying on BMI could put you at risk of countless diseases…

Visceral fat is often referred to as ‘active fat’ due to the effect it has on our hormones and body functions. It can interrupt normal hormone communications between your vital organs, and can lead to insulin resistance and eventually type 2 diabetes. Additionally, it can affect the functions of your organs and puts you at higher risk of developing heart disease or cancers including breast cancer or colorectal cancer.

So, what can you do to protect yourself?

Factors which contribute to visceral fat levels include stress, diet and exercise habits in addition to age, ethnicity and gender. Living a healthy lifestyle will therefore reduce your chances of visceral fat accumulating in your abdominal cavity.

If you are worried about your visceral fat levels the waist-to-hip ratio (found by dividing waist width by hip width) can give an indication of total fat as well as the level of visceral fat, however the most accurate measurement of visceral fat is to measure adiponectin levels in the blood.

Adiponectin (a blood analyte) is closely linked with visceral fat; low levels of adiponectin indicate high levels of visceral fat. The Adiponectin test enables true measurement of visceral fat levels and allows for more accurate measurement of health than traditional BMI; if you have been diagnosed with unhealthy BMI and believe this to be an inaccurate diagnosis, testing your adiponectin levels can help determine your true measurement of health. Simply ask your doctor for the Adiponectin test!

For health professionals:

The adiponectin test from Randox can accurately assess levels of abdominal visceral fat, independent of age, race or fitness level.  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.  Contact us now for further information.


MYTH: Only overweight people get type 2 diabetes, right?

The answer to this common myth is no. Let us tell you why…

As a condition that usually manifests later in life, type 2 diabetes is viewed by many as a self-inflicted disease caused by eating too much sugar and being overweight. Although obesity is strongly associated with type 2 diabetes it isn’t the only cause. In fact, many people of a healthy weight have type 2 diabetes, and similarly many overweight people do not. This is because an individual’s metabolic health can be affected by factors other than their weight.

Firstly, let’s define metabolic health; metabolic health refers to the body’s health at a cellular function, and one aspect of this is the body’s ability to utilise nutrients for energy. Within this insulin has an important function; insulin is a hormone produced by the pancreas and used by the body to regulate how glucose is used and stored. In some individuals, however, this is not the case; their pancreas may either not produce enough insulin, or may not be able to effectively use the insulin it produces, known as insulin sensitivity.  High blood sugar level and type 2 diabetes is the effect of this.

Whilst obesity and lack of exercise are 2 of the most common reasons affecting metabolic state and causing type 2 diabetes, it is important to note that approximately 1 in 3 type 2 diabetics are undiagnosed. Therefore the causal factors of these individuals are not included in the statistics and therefore not accounted for in this statement. Other causal factors include family history, ethnicity, age, stress, inflammation, poor diet and visceral fat.

Let’s talk about a few of these factors…

Family history & ethnicity – Do genetics play a role?

Risk factors of type 2 diabetes includes family history and ethnicity; research(1) has found that there is a 1 in 7 risk of type 2 diabetes for children whose parents were diagnosed before the age of 50, and 1 in 2 risk for children if both parents have type 2 diabetes. Furthermore, research(2) has linked genetic mutation of the HMGA1 gene to an increased risk of type 2 diabetes in white Europeans; the study found that defects in the HMGA1 gene led to a drop in the body’s ability to make insulin receptors, thus leading to insulin resistance. In fact, 1 in 10 study participants with type 2 diabetes had a genetic mutation of the gene. Furthermore certain ethnic groups have been linked to increased risk of type 2 diabetes i.e. African Americans, Native Americans, Hispanic Americans and Asian Americans; some believe this may be due to genetics.

Chronic Stress

When the body is under stress, stress hormones such as cortisol are released. These hormones can affect the body’s blood glucose levels; for example, one of the primary functions of cortisol is to provide an immediate source of energy for the body, resulting in an increase of glucose supply to the blood. Individuals suffering chronic stress therefore have a constant production of cortisol, and chronically increased blood glucose levels as a result. This increases the risk of type 2 diabetes.

Chronic stress can lead to inflammation, which is another risk factor in the development of type 2 diabetes.

Inflammation

As the body’s natural response to injury, inflammation is the initial step in the healing process. Opening the blood vessels to allow free movement of the body’s natural healing substances to the affected site, it offers the body protection and fights off foreign substances such as germs and toxins. Inflammation is necessary to rid infections and heal wounds, however if the body suffers a chronic state of inflammation it can have damaging effects; chronic inflammation is caused by autoimmune conditions, allergies, chronic stress and conditions such as Crohn’s disease, and is linked to major diseases such as heart disease, arthritis and certain cancers. The link with type 2 diabetes is a result of inflammation causing insulin resistance, increasing the risk of type 2 diabetes.

Abdominal visceral fat

Abdominal visceral fat is the fat which surrounds the internal organs in the abdominal cavity. High levels of abdominal visceral fat are associated with insulin resistance and therefore, high risk of diabetes. Abdominal visceral fat can be found in individuals of all shapes and sizes, and regardless of ‘healthy’ BMI high visceral fat levels can still occur. This is because BMI doesn’t take into account muscle mass or other factors including gender and ethnicity. This presents an issue as those with a ‘healthy’ BMI may unknowingly still be at risk of diabetes. Similarly those with high muscle mass, who are determined ‘overweight’ based on BMI, may worry that they are at risk of diabetes, when in fact their weight isn’t putting them at risk. Determining levels of abdominal visceral fat is a much better indication of health than BMI.

Overall risk of type 2 diabetes is correlated with genetic, environmental and lifestyle factors. Whilst some impact more than others, it is important to recognise that there are numerous factors related to type 2 diabetes, and rid the myth that obesity and a high sugar diet high are the only causal factors.

Help set the record straight by sharing this article:

References:

(1) American Diabetes Association (2014) Genetics of Diabetes. Found online at diabetes.org/diabetes-basics/genetics-of-diabetes.html

(2) Brunetti et al (2011) Functional Variants of the HMGA1 Gene and Type 2 Diabetes Mellitus. Journal of the American Medical Association (JAMA); 305 (9):903-912.

If you are worried about your blood glucose levels, or risk of diabetes, ask your doctor for these tests:

  • Glucose, HbA1c and Fructosamine to assess your blood glucose levels
  • CRP to determine chronic inflammation with additional testing of SPLA2-IIA levels to determine vascular inflammation
  • Adiponectin to assess your level of abdominal visceral fat. High levels of abdominal visceral fat can indicate metabolic syndrome and pre-diabetes.

For more information on diabetes testing visit our dedicated diabetes reagents page.

For health professionals:

Adiponectin is a protein which regulates the metabolism of lipids and glucose and influences the body’s response to insulin. Low levels of Adiponectin are correlated with increased CRP (increased inflammation), higher levels of triglycerides and insulin resistance. As a result of increased insulin resistance and inflammation, low levels of Adiponectin can indicate metabolic syndrome.

For more information please visit our dedicated Adiponectin page or view our full range of diabetes tests.

SPLA2-IIA is a highly specific marker of atherosclerotic plaque inflammation, and has a direct role in the formation of rupture-prone atherosclerotic plaque. Increased concentrations of SPLA2-IIA have been linked with increased risk of cardiocerebrovascular events. As a highly specific marker of vascular inflammation, it complements tests such as hsCRP, and can be used to improve the risk assessment of patients with moderate to high risk of CVD, in particular those with metabolic syndrome such as insulin resistance.

Further reading: Sertić et al (2010) Does Lp-PLA2 determination help predict atherosclerosis and cardiocerebrovascular disease? Acta Med Croatica. 64(4):237-45

Randox SPLA2-IIA will be available soon. To register your interest please view our dedicated SPLA2-IIA page.


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