Differentiating Type 1 and Type 2 Diabetes Mellitus
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
- World Health Organization. Diabetes. World Health Organisation. Published April 5, 2023. Accessed April 25, 2023. https://www.who.int/news-room/fact-sheets/detail/diabetes
- The Misdiagnosis of type 1 and type 2 diabetes in adults. The Lancet Regional Health. 2023;29:100661-100661. doi:https://doi.org/10.1016/j.lanepe.2023.100661
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-
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The Silent Diabetes Pandemic: A Randox Reagents Blog
The Silent Pandemic
A striking statistic is that an estimated 4.2 million people die annually from Diabetes complications and it is anticipated it will be the seventh leading cause of death by 2030.
Type 2 diabetes mellitus (T2DM) has reached the status of ‘global pandemic’, a phrase we have become all too familiar with due to the current global Covid-19 pandemic, but one we now know not take for granted.
Diabetes is a chronic, potentially life-threatening disease and can cause a myriad of health complications which affect the feet, eyes, kidneys, and cardiovascular health.
Early detection and treatment of diabetes is key, particularly as many people with type 2 diabetes have no signs or symptoms but do have associated risk factors.
Randox is committed to raising awareness of preventative healthcare related to Diabetes through advancing diabetes testing capabilities, including diabetes diagnosis & monitoring, and monitoring of associated complications including; ketoacidosis, renal dysfunction, and metabolic status.
The Randox Diabetes testing panel consists of ten assays including niche and superior performance assays that are compatible with a wide range of clinical chemistry analyzers.
Contact Us
Find out more about the Randox diabetes reagents panel or alternatively you can contact us
reagents@randox.com | www.randox.com/diabetes-reagents
Product availability may vary from country to country. Some products may be for research use only. For more information on product application & availability, please contact your local Randox Representative
Diabetes Reagents Panel
Diagnosis & Monitoring
Fructosamine (Glycated Protein) (Enzymatic Method)
Ketoacidosis
Renal Dysfunction
Creatinine (Enzymatic & JAFFE Methods)
Metabolic Status
The Keto Diet: Are the risks worth the benefits?
Diet trends have continued to evolve throughout the years with a strong influence from celebrities. Beginning in the 1930s the grapefruit diet aka the “Hollywood diet” started which encouraged eating a grapefruit with every meal. More recently an increasing amount of extreme diet trends have emerged. In 2004, Beyoncé started the master cleanse involving a concoction of hot water, lemon juice, maple syrup and cayenne pepper and even crazier was Reese Witherspoon’s “baby food diet”. The newest trend to materialise is the keto diet favoured by celebrities including Halle Berry and the Kardashians. However, the results for long term weight loss and the safety of the diet is still questioned.
What is the ketogenic diet?
The ketogenic diet is a low carb diet which involves drastically reducing carbohydrate intake and replacing it with fat. Initially, the purpose of the ketogenic diet was not to aid weight loss but was prescribed to aid in the treatment of tough-to-control epileptic seizures that were unresponsive to drugs. In the 1920s the diet was found to significantly reduce the frequency of seizures in children. However, the benefits for weight loss have also been realised as the carbohydrate reduction kicks the body into a natural fat burning state called ketosis. By starving the body of carbohydrates and sugars, the first fuel the body burns, the body looks for another source of fuel to retrieve its energy. The body becomes efficient at burning fat for energy whilst also turning fat into ketones in the liver which can supply the brain with energy.
Ketosis
The metabolism of fatty acids in the liver results in the production of ketone bodies. These comprise of three chemicals consisting of acetone (2%), acetoacetate (20%) and D-3-Hydroxybutyrate (78%) and this production is called ketogenesis. The ketone bodies are produced by the chemical acetyl-CoA predominantly in the mitochondrial matrix of liver cells. This process is necessary in small amounts particularly when carbohydrates are scarce, and glucose is not available as a fuel source.
The ketone bodies are water soluble allowing for the transportation across the inner mitochondrial membrane as well as across the blood brain barrier and cell membranes. This allows them to source the brain, heart and muscle with fuel. Interestingly, during starvation they are the major energy source for the brain, providing up to 75%.
The excess production of ketones can accumulate in the body creating a state of ketosis. This stage, although abnormal, is not considered harmful, which is why it is being promoted as a diet craze. However, due to the acidic nature of the ketone bodies, particularly D-3-Hydroxybutyrate, larger amounts of ketone bodies can cause the pH levels in the body to drop to dangerously acidic levels creating a state of ketoacidosis.
Ketoacidosis
The benefits of the keto diet have been well advertised and received a lot of celebrity support. With powerful celebrities such as Halle berry ‘swearing by it’ as it allows her to manage her diabetes, it is easy to see why so many are keen to try it. However, with little to no information about the long-term effects, should we be finding out more before trying it ourselves?
In 2006, a study was conducted reviewing the influence of a low-carbohydrate diet can have on ketoacidosis. In this study the patient who had no history of diabetes was placed on a strict low carbohydrate diet for four years. Although the patient showed a significant decrease in weight on the diet, they also experienced four episodes of ketoacidosis. Each time an episode occurred the patient was administered intravenous fluids and insulin which lead to their recovery, however each time they returned to the diet it wasn’t long before another ketoacidosis episode occurred. When the patient was placed on a diet containing normal amounts of carbohydrates their glucose levels returned to normal, preventing a ketoacidosis episode from occurring again. The more ketones in the blood, the more ill a person with ketoacidosis will become. Left untreated ketoacidosis can cause potentially fatal complications such as severe dehydration, coma and swelling of the brain.
Randox D-3-Hydroxybutyrate (Ranbut) Reagent
Randox Reagents offer a D-3-Hydrobutyrate assay designed to measure the major ketone lvels in the body, D-3-Hydroxybutyrate, allowing for an efficient diagnosis to be implemented. The superior methodology provides more accurate, reliable and specific results compared to the traditional dipstick method of ketone body measurement.
The benefits of the Randox D-3-Hydroxybutyrate (Ranbut) assay include:
- Excellent precision of less than 3.5% CV
- Exceptional correlation coefficient of r=0.9954 when compared against other commercially available methods.
- A wide measuring range of 0.100 – 5.75mmol/l, comfortably detecting levels outside of the healthy range, 0.4 – 0.5mmol/l.
- Enzymatic method for accurate and reliable results
- Reconstituted stability of 7 days when stored between +2 to +8⁰C
References
- Ketoacidosis during a low-carbohydrate diet. Shah, Panjak and Isley, William. s.l. : The new england journal of medicine, 2006, Vol. 354.
Instrument Specific Applications (ISA’s) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.
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