Diabetes mellitus is a metabolic disease that occurs at all ages in which there is an increase in blood sugar due to either the absence of insulin, which facilitates tissue metabolism of glucose, or the impossibility of insulin to exert its action in peripheral tissues (insulin resistance).
Diabetes begins more insidiously or brutally with symptoms such as intense thirst with increased water consumption (polydipsia), weight loss, increased urination (polyuria), increased appetite (polyphagia), going up to ketoacidosis and diabetic coma as a result of hyperglycemia.
Diabetes mellitus is broadly divided into three types:
Type I diabetes requires injectable insulin treatment for metabolic balancing, and type II diabetes is treated with oral medication associated with changes in lifestyle, diet and increased physical activity. It can also progress to injectable treatment.
Diabetes is a disease with a chronic evolution, marked by the appearance of acute complications - hypo/hyperglycemic crises, especially in type I diabetes - and chronic complications - retinopathy, nephropathy, neuropathy, cardiopathy, etc. These complications can significantly affect the patient's quality of life and shorten the diabetic's life expectancy.
Recent scientific data showed that adult diabetes is much more heterogeneous and that the current division into type 1 and 2 is too simplistic in relation to the complexity of the disease, the high percentage of wrong diagnosis, the severity of the evolution and the potential complications. Not all diabetic patients evolve equally badly, nor is the risk of complications evenly distributed among the entire mass of diabetics. There are diabetic patients who progress more rapidly and develop complications more quickly than other patients. Therefore, recent research on cohorts of adult diabetics of both types/sex, used common physico-biological parameters and proposed a reclassification of diabetes into five subtypes, which would allow to identify the subtypes associated with a more severe evolution or the early appearance of some complications.
Identification of diabetes subtypes and the required tests
A new classification of diabetes, into five subtypes (clusters), was recently proposed by Ahlqvist et al.(1) - ANDIS-HOMA2 study - by clustering based on five parameters - age at onset of diabetes in years, glycosylated hemoglobin expressed in mmol/mol, body mass index, residual activity of pancreatic β-pancreatic cells (HOMA2-β) and peripheral insulin resistance (HOMA2-IR) - of the data of a study group of about 10000 subjects (ANDIS cohort). The last two parameters are calculated using the HOMA2 homeostatic model (HOMA2 Calculator) and you need the values of plasma glucose (expressed as mmol/l or mg/dl) and insulinemia (expressed as pmol/l or µU/ml). Instructions for calculating these values are here. Details on the availability of this HOMA2 calculator at contact@metabolicanalysis.eu. The study ANDIS-HOMA2 showed the existence of five subtypes of diabetes:
While the SAID subtype corresponds to the current autoimmune type 1 diabetes and LADA diabetes (latent autoimmune diabetes of the adult), the study identified two new, severe subtypes of diabetes, namely SIDD and SIRD, which are currently masked by type I (SIDD) and type II (SIRD) diabetes, respectively. This classification is valid for populations of Caucasian origin, in Europe and North America, as well as the Chinese population(2) and is available via the button Identification of diabet subtypes, option ANDIS-HOMA2 study.
Another study (3) also did clustering based on five variables (three of them common to the study ANDIS-HOMA2) - age at onset of diabetes, glycosylated hemoglobin, body mass index, plus HDL cholesterol (expressed in mmol/l) and C-peptide (expressed in mmol/l) - in three international patient cohorts, namely All New Diabetics in Scania (ANDIS), the one on which the initial clustering was done with the data provided by the HOMA2 calculator, Diabetes Care System (DCS), and Genetics of Diabetes Audit and Research Tayside Study (GoDARTS). In these three studies, five subtypes of diabetes were also identified, similar to those in the study ANDIS-HOMA2:
The application implements these algorithms of similarity - Euclidean distance and cosine similarity - and allows the comparison of the data of any diabetic patient with the median value of the data of the patients in the study. Enter your patient details - age at onset of diabetes, glycosylated hemoglobin, body mass index, plus HOMA2β/HOMA2-IR or HDL-cholesterol/C-Peptide vlueas, and the algorithm will compare your patient's data with the median value of the data of the patients in the study. The app will show you how the patient data matches each diabetes subtype in the study, with the highest percentage indicating the best match.
1. Ahlqvist E et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018 May;6(5):361-369. doi:10.1016/S2213-8587(18)30051-2. Epub 2018 Mar 5. Article
2. Xiantong Zou, Xianghai Zhou, Zhanxing Zhu, Linong Ji. Novel subgroups of patients with adult-onset diabetes in Chinese and US populations. Lancet Diabetes Endocrinol. 2019 Jan;7(1):9-11. doi:10.1016/S2213-8587(18)30316-4. Article
3. Roderick C et al. Replication and cross-validation of type 2 diabetes subtypes based on clinical variables: an IMI-RHAPSODY study. Diabetologia. 2021; 64(9): 1982-1989. doi: 10.1007/s00125-021-05490-8 Article
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