Historical Notes
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.

Epidemiology
Worldwide, approximately 828 million adults have diabetes mellitus, corresponding to a prevalence of 14% of the adult population. About 10% of these cases are type 1 diabetes, i.e., around 80 million adults.

• In the USA, about 38 million people (11.6% of the population) have diabetes, with type 1 diabetes making up 5.7% of diagnosed adult cases.
• In Europe, around 32 million people have diabetes, with 5–10% of cases being type 1.
• In India, the number of people with diabetes is increasing dramatically. Around 212 million people have the disease, representing roughly 26% of the global diabetes population, with type 1 accounting for 5–10%.

Diabetes mellitus is a global challenge for health systems worldwide.

Definition
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:

1. Type 1 Diabetes Mellitus – An autoimmune disease leading to destruction of pancreatic beta cells, resulting in absolute insulin deficiency.
2. Type 2 Diabetes Mellitus – A combination of insulin resistance and relative insulin deficiency with secretion defects.
   • Type 2A: without obesity
   • Type 2B: with obesity
3. Type 3 Diabetes Mellitus – Other specific types:
   • Genetic defects of beta cells (e.g., MODY diabetes)
   • Genetic defects in insulin action
   • Diseases of the pancreas and islets of Langerhans (pancreoprivic diabetes)
   • Drug- or chemical-induced diabetes
   • Infection-induced diabetes
   • Unusual forms of immune-mediated diabetes
4. Type 4 Diabetes Mellitus – Gestational diabetes

Proposed 5-Cluster Classification (Swedish research group):

LADA – Latent Autoimmune Diabetes in Adults
Belongs to SAID group. Autoantibody-positive, often misdiagnosed as type 2. Insulin required later than in type 1.

Typical Features:

• Age at diagnosis >30 years
• Positive autoantibodies (especially GAD)
• Initially no insulin therapy needed, later required
• Slower progression than classic type 1
• C-peptide initially normal, later declines

Autoantibodies in Diabetes
Help identify autoimmune forms of the disease.

• GAD – most important marker for LADA and type 1 in adults
• IA-2 – often in children with type 1
• ZnT8 – increases diagnostic sensitivity
• IAA – useful in young children before insulin therapy

Associated Autoimmune Diseases with Type 1 Diabetes

• Autoimmune thyroiditis (Hashimoto, Graves)
• Celiac disease
• Addison’s disease
• Vitiligo
• Pernicious anemia
• Autoimmune hepatitis
• Rheumatoid arthritis, SLE
• Myasthenia gravis (rare)

Polyendocrine Autoimmune Syndromes (APS)

• APS Type 1 – Childhood onset, multiple endocrine glands affected (AIRE gene)
• APS Type 2 – Adult onset, Addison + autoimmune thyroiditis ± type 1 diabetes
• APS Type 3 – Thyroiditis + another autoimmune disease (no adrenal involvement)

Carpenter Syndrome – unrelated genetic malformation syndrome (RAB23 mutation).

Diagnosis
In non-pregnant individuals, diagnosis can be made via plasma glucose or HbA1c:

• HbA1c > 6.5% (>48 mmol/mol)
• Fasting plasma glucose > 126 mg/dL (7 mmol/L)
• 2-hour OGTT glucose > 200 mg/dL (>11.1 mmol/L)
• Random plasma glucose > 200 mg/dL with classic symptoms

Prediabetes:

• HbA1c 5.7–6.4% (39–47 mmol/mol)
• Fasting glucose 100–125 mg/dL (5.6–6.9 mmol/L)