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 transition period between late pregnancy and the onset of lactation requires quick metabolic adaption by dairy cattle as foetal growth, calving and the onset of lactation causes increased energy demands on the body. To support the increase in energy requirements, increased nutrients are required; however, limitations to dietary intake can occur as a result of reduced appetite caused by the growing foetus restricting the size of the rumen. In addition, during this period almost all glucose intake is utilised for lactose synthesis. As a result, during the transition period dairy cattle can be prone to negative energy balance.
Negative energy balance occurs when energy demands exceed dietary intake, and in cases where energy requirements are not met by diet, dairy cattle will utilise their own fat reserves as an energy source; this being non-esterified fatty acids (NEFA), a major component of triglycerides (fats) in the body. Excessive metabolism of NEFA, however, can result in accumulation of fat which can result in fatty liver disease (resulting in decreased liver function), and ketosis which can be toxic and damaging to the liver and kidneys (it has been associated with pregnancy complications, decreased milk production and hypoglycaemia).
Additionally, during the transition period, as a result of the increase in metabolic processes, dairy cattle are more susceptible to metabolic stress. This is due to the increase in Reactive Oxygen Species (ROS).
ROS are free radical by-products of normal metabolic processes which can be harmful and destructive to the cells in the body. To defend against them the body utilises antioxidants to inhibit the formation of free radicals, destroy free radicals or repair the damage caused by free radicals; however if there is an imbalance of antioxidants to ROS then the body’s natural defence system is decreased. This can result in free radical damage to surrounding cells, tissue and DNA.
Free radicals have been implicated in many disease states in addition to suppression of the immune response system. As a result, in the first 10 days after calving dairy cows are at maximum risk of infectious and metabolic disorders; in fact, approximately 75% of disease occurs in herds within the first month of lactation (Abuelo et al. 2014). Complications for dairy cattle suffering metabolic stress include not only fatty liver disease and ketosis, but also mastitis, retained foetal membranes, reduced milk production and increased risk of cancer, CVD, lung, liver and renal disease, inflammatory conditions such as arthritis, infectious conditions, and, neurological disorders.
How can the health and well-being of dairy cattle be protected during the transition period?
To ensure animal well-being, and indeed reduce economic impact for dairy farmers, dairy cattle should be monitored for their antioxidant capacity, particularly during pregnancy. As the antioxidant defence system includes many components, the Total Antioxidant Status (TAS) test is used to assess overall antioxidant capacity. This test is beneficial in gaining an overall view of the body’s ability to defend against free radical attack; it can therefore help to determine if nutritional supplements are required to ensure good body condition during the transition period. Further antioxidant testing may be required to ensure nutritional requirements are fully understood before antioxidant supplementation begins.
In addition, the NEFA test indicates negative energy balance, and can therefore be used to monitor whether their nutrient intake is adequate for the high energy demands experienced during the transition period. Additionally, research (Li, H.Q et al. 2016) has found that supplementing dairy cattle with rumen-protected folic acid (RPFA) may benefit negative energy balance by decreasing plasma concentrations of NEFA and increasing glucose plasma. Results show increased milk protein levels and improved nutrient ingestion, milk production and reproductive performance.
Abuelo A., Hernandez J. and Beneditor J.L (2014) The importance of oxidative status of dairy carrel in the periparturient period: revisiting antioxidant supplementation. Journal of Animal Physiology and Animal Nutrition. 99(6):1003-1016
Li, H. Q., et al. (2016) Effects of dietary supplements of rumen-protected folic acid on lactation performance, energy balance, blood parameters and reproductive performance in dairy cows. Animal Feed Science and Technology
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