Diabetes mellitus is a group of disorders of carbohydrate metabolism in which glucose is both underutilized (due to reduced glycogenolysis) and overproduced (due to increased gluconeogenesis). This imbalance causes elevated blood sugar levels.
Diagnosis can be made through elevated plasma glucose or increased HbA1c. In 1998, diabetes mellitus was classified into four types:
Type 2 Diabetes: A very heterogeneous group
In addition to very specific forms of diabetes (Type 3 diabetes), newly diagnosed diabetes mellitus is usually classified as either Type 1 or Type 2.
People with Type 1 diabetes are typically treated with insulin right away (since Type 1 diabetes is defined by an absolute lack of insulin).
In people with Type 2 diabetes, however, the initial therapy and response to treatment vary widely — often leading to a process of “trial and error.”
The chosen therapy depends heavily on the treating physician, which can result in under- or overtreatment. The group of people with Type 2 diabetes is therefore very heterogeneous.
Experienced clinicians consider factors such as age, abdominal fat, and the dynamics of disease progression; however, a systematic and comparable classification has not yet been established.
Five subgroups in newly diagnosed Type 2 diabetes: A fairly stable pattern
A Swedish research group proposed a new classification for Type 2 diabetes in 2018 [1]. This proposal was based on a study of nearly 9,000 individuals with newly diagnosed Type 2 diabetes. They identified six relevant variables on which to base their classification:
Using these six variables, the researchers identified five subgroups among the 9,000 participants:
Interestingly, the percentage distribution among other populations with newly diagnosed diabetes mellitus was very similar. This suggests that the classification may be a useful model for structuring the highly heterogeneous group of people with Type 2 diabetes.
Classification into five “clusters”: Practical implications?
Long-term follow-up data show that these groups differ in required therapy as well as in risk and distribution of complications.
Thus, these “clusters” may help support the goal of personalized therapy (precision medicine) in modern diabetes care.
For example:
Conclusion
Reference:
[1] Ahlqvist E, Storm P, Käräjämäki A, 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–
Cluster | Key Features | Autoantibodies | BMI | C-peptide | Insulin Resistance | Therapy |
SAID (Severe Autoimmune Diabetes) | Type 1-like, young, early insulin need | + | Low | Low | Low | Insulin |
SIDD (Severe Insulin-Deficient Diabetes) | Young, no antibodies, severe insulin deficiency | – | Low | Low | Low | Insulin ± GLP-1/SGLT2 |
SIRD (Severe Insulin-Resistant Diabetes) | High BMI, preserved β-cells, high risk kidney/NAFLD | – | High | Normal/high | High | Metformin, GLP-1, SGLT2 |
MOD (Mild Obesity-related Diabetes) | Young, overweight, mild progression | – | High | Normal | Moderate | Lifestyle ± oral meds |
MARD (Mild Age-Related Diabetes) | Older age, mild course | – | Normal | Normal | Low | Lifestyle ± Metformin |
Belongs to SAID group. Autoantibody-positive, often misdiagnosed as type 2. Insulin required later than in type 1.
Typical Features:
Feature | LADA |
Age at diagnosis | >30 years |
Autoantibodies | GAD+ (main marker) |
Insulin need | Delayed (months–years) |
Progression | Slower than type 1 |
C-peptide | Initially normal → declines |
Therapy | Initially oral meds (Metformin, DPP-4i), insulin later; avoid sulfonylureas |
Diabetes mellitus has been known as a disease for over 3,500 years. In the second century AD, a Greek physician used the term Diabetes (Greek for “to flow through”) to describe the symptom of frequent urination associated with the disease. In India, the first mention appeared around 600 BC in Ayurvedic texts. The condition was called “honey-sweet urine” or “honey urine” because it was observed that the urine had a sweet taste and attracted ants. In China, diabetes was mentioned around 200 BC, where it was called “wasting thirst disease” or “consuming thirst,” with the main symptoms—intense thirst, frequent urination, and weight loss—clearly described.
In the 17th century, Thomas Willis recognized that the urine of diabetics tasted sweet, and in the 19th century it was understood that diabetes is related to a disturbance in sugar metabolism.
Historical Notes
Time / Region | Observation |
~600 BC (India) | First mention in Ayurvedic texts; called honey-sweet urine (sweet taste, attracted ants). |
~200 BC (China) | “Wasting thirst disease” – intense thirst, frequent urination, weight loss described. |
2nd century AD (Greece) | Term Diabetes (“to flow through”) coined for frequent urination. |
17th century (Thomas Willis) | Urine of diabetics noted to taste sweet. |
19th century | Recognized as disorder of sugar metabolism. |
Region | Diabetes Cases (millions) | % of Type 1 |
Worldwide | 828 | ~10% |
USA | 38.4 | ~5.7% |
Europe (EU) | 31.6 | ~5–10% |
India | 212 | ~5–10% |
China | 140 | <5% |
Latin America | 35 | ~2.3% |
Antibody | Target | Relevance | Typical Use |
GAD-AK | Glutamate decarboxylase (GAD65) | Most frequent in LADA; sensitive in adults | LADA, Type 1 |
IA-2-AK | Tyrosine phosphatase IA-2 | More common in children; faster β-cell loss | Type 1 |
ZnT8-AK | Zinc transporter 8 | Improves sensitivity; esp. in GAD-/IA-2–negative | Type 1 |
IAA | Insulin | Only useful pre-insulin therapy; young children | Early type 1 |
ICA | Islet cell antibodies | Historic, less specific | Rarely used |
Disease | Notes / Screening |
Autoimmune thyroiditis (Hashimoto, Graves) | Most common (15–30%); TSH, fT4, TPO-AK |
Celiac disease | 4–8%; tTG-IgA, total IgA |
Addison’s disease | Rare; cortisol, ACTH, 21-OH-AK |
Vitiligo | Depigmentation |
Pernicious anemia | B12 deficiency, intrinsic factor AK |
Autoimmune hepatitis | Liver enzymes, ANA, SMA |
Rheumatoid arthritis / SLE | Less common |
Myasthenia gravis | Very rare |
Type | Name / Common Features | Genetics |
APS-1 | Addison + hypoparathyroidism + candidiasis | Childhood; AIRE mutation |
APS-2 | Addison + thyroiditis ± type 1 DM | Adolescence/adults; HLA-linked |
APS-3 | Thyroiditis + other autoimmune (no adrenal) | Common; no adrenal involvement |
Test | Diabetes | Prediabetes |
HbA1c | ≥6.5% (≥48 mmol/mol) | 5.7–6.4% (39–47 mmol/mol) |
Fasting plasma glucose | ≥126 mg/dL (≥7.0 mmol/L) | 100–125 mg/dL (5.6–6.9 mmol/L) |
2h OGTT | ≥200 mg/dL (≥11.1 mmol/L) | 140–199 mg/dL (7.8–11.0 mmol/L) |
Random glucose + symptoms | ≥200 mg/dL (≥11.1 mmol/L) | – |
Diagnosis should be confirmed by a second method unless classic symptoms are present.