Diabetes: Definition, Etiology, Clinical Manifestations, Diagnosis, and Treatment Highlights

代表糖尿病诊断与治疗的临床场景特写，胰岛素笔和血糖仪摆放在诊室桌面

Diabetes is a group of metabolic diseases characterized by chronic hyperglycemia, primarily classified into type 1 and type 2 with distinct pathophysiological mechanisms. This article provides a systematic review of the definition, major causes, common clinical presentations, 1999 WHO diagnostic criteria, and integrative treatment principles to facilitate clinical recognition and management.

Terminology and Definition

Diabetes mellitus (DM) is a metabolic disease caused by absolute or relative insulin insufficiency and decreased insulin sensitivity, characterized by elevated blood glucose levels, often accompanied by lipid abnormalities. In traditional Chinese medicine (TCM), it is categorized under “Xiaoke” and “Pidan.”

Etiological Factors

Scene depicting unhealthy lifestyle factors increasing diabetes risk: a sedentary person on a sofa with fast food and sugary drinks

TCM Etiology and Pathogenesis

  • Dietary Factors: Excessive intake of greasy, sweet, and rich foods or improper dietary structure are primary causes. The “Neijing” states: “Overeating injures the stomach and intestines” and “Greasy foods cause internal heat, sweet foods cause fullness.” Fatty and sweet foods stagnate the stomach and impair the spleen, causing mid-jiao obstruction, disordered ascending and descending Qi, accumulation of dampness and phlegm, which transform into heat and injure body fluids over time, leading to Xiaoke.
  • Physical Inactivity: Reduced activity leads to spleen Qi stagnation and malfunction of transportation and transformation; spleen and stomach weakness results in impaired distribution of essential nutrients, internal generation of damp-phlegm and turbid fluids, gradually transforming into heat that triggers the disease.
  • Emotional Disturbances: Liver Qi stagnation causes middle jiao Qi constraint, disharmony between liver-spleen and liver-stomach; spleen and stomach transport function is impaired, causing food retention with heat and phlegm accumulation, gradually resulting in Xiaoke.

Western Medicine Etiology and Pathophysiology

  • Type 1 Diabetes Mellitus (T1DM): Associated with genetic, environmental, and autoimmune factors. The human leukocyte antigen (HLA) located at chromosome 6p21 is considered the primary susceptibility gene, alongside multiple other gene loci. Both humoral and cellular immunity mediate insulitis and selective β-cell damage. Certain viruses (e.g., mumps, Coxsackie B4, rubella), chemical substances, and food proteins (e.g., cow milk protein) can trigger autoimmune islet damage, leading to β-cell apoptosis and disease onset.
  • Type 2 Diabetes Mellitus (T2DM): A complex disease resulting from the interplay of genetic and environmental factors. Common susceptibility genes such as TCF7L2, PPAR-γ, KCNJ11 affect various aspects of glucose metabolism. Triggers include obesity, unhealthy diet, physical inactivity, low birth weight, and GLP-1 deficiency. The core pathogenesis involves insulin resistance (pre-receptor, receptor, and post-receptor defects) and β-cell dysfunction (influenced by genetics, glucotoxicity/lipotoxicity/Islet Amyloid Polypeptide toxicity, GLP-1 deficiency), manifesting as insufficient insulin secretion, secretory defects, and rhythm disorders.

Clinical Manifestations

Home scenario showing typical diabetes symptoms: polydipsia, polyuria, and fatigue in an adult holding a water bottle looking exhausted

The classic symptoms include polydipsia, polyphagia, polyuria, and weight loss. About 50% of type 2 diabetes patients exhibit insidious onset with no obvious symptoms; approximately 80% first present with symptoms such as skin or vulvar itching, purulent skin infections, or blurry vision.

Symptoms

  • Main symptoms: excessive thirst and drinking, frequent urination with large volume, foamy or sweet-smelling urine; increased hunger and markedly increased food intake compared to usual.
  • Other symptoms: physical weakness, fatigue, irritability, insomnia with vivid dreams, forgetfulness, soreness in the lower back and knees; women may experience increased vaginal discharge and menstrual irregularities.

Signs

Early stages often lack specific signs. With complications, corresponding signs may appear, such as early-phase hyperactive tendon reflexes in diabetic neuropathy, progressing to decreased or absent reflexes in later stages.

Diagnostic Criteria (WHO 1999)

Close-up of clinical blood sampling scene for blood glucose testing in diabetes diagnosis

Test Item Conditions Diagnostic Threshold
Random Plasma Glucose (RPG) With polyuria, polydipsia, and unexplained weight loss ≥ 11.1 mmol/L (200 mg/dL)
Fasting Plasma Glucose (FPG) Fasting ≥ 8 hours ≥ 7.0 mmol/L (126 mg/dL)
Oral Glucose Tolerance Test (OGTT) 2-hour plasma glucose Oral 75 g anhydrous glucose ≥ 11.1 mmol/L (200 mg/dL)
  • Note: In the absence of acute metabolic decompensation, any abnormal test should be confirmed by repeat testing on a different day; a third OGTT is not recommended.

Differential Diagnosis

Outpatient doctor performing thyroid palpation for differential diagnosis of thyroid disease

Non-Glucose Glycosuria

  • Lactosuria: Seen in lactating women, pregnant women, or infants.
  • Fructosuria and pentosuria: May occur after large fruit intake; some cases are rare congenital metabolic disorders.

Non-Diabetic Glycosuria

  • Transient “starvation glycosuria” may occur after a large carbohydrate intake following fasting.
  • Some healthy individuals may show transient glycosuria after high or rapid carbohydrate absorption.
  • Post-gastrectomy or hyperthyroidism may cause temporary glycosuria with hypoglycemic symptoms; nephritis and nephropathy with tubular reabsorption defects can cause renal glycosuria.
  • Reducing substances like uric acid, vitamin C, glucuronic acid, or medications excreted in urine such as isoniazid, penicillins, cardiac glycosides, or thiazide diuretics can lead to false-positive urine glucose tests.

Hyperthyroidism

Characterized by symptoms of high metabolism including excessive hunger, thirst, heat intolerance, sweating, irritability, and elevated thyroid hormones. Differentiated from diabetes by features such as exophthalmos, anterior neck goiter, and absence of classic diabetic symptoms like polyuria, polydipsia, and glycosuria.

Treatment

Nurse demonstrating insulin pen injection technique to patient in outpatient clinic close-up

Western Medicine Treatment Principles

Type 1 Diabetes Mellitus

  • Early initiation of intensive insulin therapy is recommended, with highly individualized dose setting and adjustment, aiming to minimize hypoglycemia.
  • Other options: pancreas or islet cell transplantation (mainly for brittle diabetes with complete islet function loss, often combined with renal transplantation), stem cell therapy (currently under clinical research and observation, not yet routine).
  • Oral hypoglycemic agents are generally not recommended for T1DM.

Simple Pathway for Type 2 Diabetes Glycemic Management

  • Foundation: lifestyle intervention.
  • If glycemic control is inadequate (HbA1c ≥ 7.0%):
  • First-line monotherapy with metformin.
  • If ineffective: add a second oral or injectable hypoglycemic agent to metformin, including:
  • Insulin secretagogues (sulfonylureas or glinides)
  • Alpha-glucosidase inhibitors
  • DPP-4 inhibitors
  • Thiazolidinediones
  • SGLT2 inhibitors
  • GLP-1 receptor agonists
  • Insulin
  • If dual therapy still insufficient: triple therapy with agents of different mechanisms.
  • If glycemic control remains poor: promptly initiate insulin therapy, options include basal insulin combined with mealtime insulin or multiple daily premixed insulin injections; metformin can be continued as needed.
  • Goals and regimens should be individualized and progressively adjusted.

Traditional Chinese Medicine Treatment Principles

  • Primarily applied for type 2 diabetes based on syndrome differentiation and use of proprietary Chinese medicines. Patients on long-term medication require regular blood glucose and liver/kidney function monitoring.
  • If glycemic control is inadequate, combined or adjusted treatments should be considered.
  • Medication Notes: Some integrated Chinese-Western compound preparations (e.g., Xiaoke Pills, Xiaotangling Capsules, Shiwei Antidiabetic Granules, Tangwei Capsules) contain Western drug components such as glibenclamide, an insulin secretagogue, with potent hypoglycemic effects. Usage requires attention to indications, contraindications, and hypoglycemia risk, especially when used with other Western medications.

Clearly classifying diabetes type and etiology assists in developing personalized treatment strategies and early identification to reduce complication risks. Type 2 diabetes management is based on lifestyle modification, with stepwise addition of oral agents or insulin when necessary; TCM syndrome differentiation and proprietary medicines can serve adjunctive roles but require caution regarding interactions and safety. Regular follow-up and complication screening are essential for long-term management.