An etiologically (causally) based classification according to the recommendations of the American Diabetes Association (ADA) and WHO is shown in the table below.
Classification of diabetes mellitus
I. Type 1 diabetes mellitus – absolute insulin deficiency due to destruction (destruction) of ß-cells (site of insulin production):
- Type 1a: immunologically mediated form Special form: LADA (latent autoimmune diabetes (with onset) in adults) – type 1 diabetes with manifestation in adulthood (> 25 years); insulin deficiency develops relatively slowly. No insulin requirement in the first 6 months, detection of GAD-Ak (glutamic acid decarboxylase; English : glutamic-acid-decarboxylase = GAD; a ß-cell-specific enzyme).
- Type 1b: idiopathic form/disease that develops without a tangible cause (rare in Europe).
II Type 2 diabetes mellitus – 4 factors in varying degrees of severity underlie this:
- Insulin resistance (reduced or abolished effect of the hormone insulin).
- Secretory (“concerning secretion”) defect of the ß-cells.
- Secretory defect of the A cells (hyperglucagonism/increased secretion of glucagon → blood glucose level ↑)
- Progressive apoptosis (programmed cell death) of ß cells.
III. other specific forms of diabetes with a known cause
- A. Genetic defects of β-cell function (autosomal dominant inheritance) – “Maturity-onset diabetes of the young” (MODY) without auto-Ak detection and obesity. Manifestation before the age of 25. Approximately 1% of all diabetics. There are currently 11 known forms, of which the following are the four most common forms responsible for approximately 90% of all MODY cases (all other forms of MODY diabetes occur ≤ 1% and are therefore not listed here):
MODY form Gene Abbreviation Chromosome PPh Notes MODY 1 (approx. 3 %) Hepatocyte nuclear factor 4 alpha HNF-4alpha 20q Reduced insulin secretion, decreased glycogen synthesis. Low triglycerides (blood lipids). MODY 2 (approx. 15 %) Glucokinase GK 7p Reduced insulin secretion Mild course, usually without late complications MODY 3 (approx. 70 %) Hepatocyte nuclear factor 1 alpha HNF-1alpha 12q Reduced insulin secretion Renal (“kidney-related”) glucosuria (excretion of glucose in the urine) MODY 5 (approx. 3%) Hepatocyte nuclear factor 1 beta HNF-1beta 17q Reduced insulin secretion Renal cysts, malformation of the genital (malformation of the sex)
- B. Genetic defects of insulin action.
- C. Diseases of the exocrine pancreas/disease of the pancreas associated with insufficient production of digestive enzymes (chronic pancreatitis/chronic pancreatitis): diabetes mellitus secondary to a pancreatic tumor is also called type 3c diabetes
- D. Endocrinopathies/diseases caused by impaired function of endocrine glands or the defective action of hormones (acromegaly, aldosteronom, Cushing’s syndrome, glucagonom, hyperthyroidism, pheochromocytoma, somatostatinoma).
- E. Drug-induced (e.g., glucocorticoids, thyroid hormones, betaadrenergics, thiazides, hormonal contraceptives); see also under “Diabetogenic effects due to drugs”
- F. Infections (e.g., congenital rubella infection, CMV infection).
- G. Rare immunologically determined forms (e.g., anti-insulin receptor antibodies).
- H. Genetic syndromes that are occasionally associated with diabetes (e.g., Down syndrome, Klinefelter syndrome, Turner syndrome)
IV. Gestational diabetes (GDM)
Proposal for a new classification
The authors, led by Professor Leif Groop of the Lund University Diabetes Center in Sweden, propose a subdivision into five forms in adults based on age at diagnosis, BMI, HbA1c, beta-cell function, insulin resistance, and autoantibodies:
- Cluster 1: Severe autoimmune diabetes (essentially LADA diabetes: latent insulin-dependent diabetes mellitus in adults); manifestation in younger adulthood; destroyed beta cells no longer produce insulin (6-15%).
- Cluster 2: Severe insulin deficiency (similar to cluster 1). Affected individuals are usually young and slim; no autoantibodies, immune system is not defective (9-20%).
- Cluster 3: Severe insulin resistance; patients are usually overweight, they no longer respond adequately to insulin, high risk of nephropathy (11-17%).
- Cluster 4: Mild diabetes combined with obesity. Affected individuals are usually severely overweight, but metabolism is less disturbed than in patients in cluster 3 (18-23%).
- Cluster 5: Mild diabetes elderly patients; symptoms begin at an older age compared to the other clusters (39-47%).
According to the researchers, all five forms were genetically distinct, so they are different types rather than stages of disease. Furthermore, the authors pointed out that many cluster 1+2 patients were not receiving insulin at manifestation.
