Diabetes Mellitus (โรคเบาหวาน)

• ICD-10:
  • E10 – Type 1 diabetes mellitus
  • E11 – Type 2 diabetes mellitus
  • E13 – Other specified diabetes mellitus
  • E14 – Unspecified diabetes mellitus
• ICD-11:
  • 5A10 – Type 1 diabetes mellitus
  • 5A11 – Type 2 diabetes mellitus
  • 5A12 – Secondary diabetes mellitus
  • 5A13 – Gestational diabetes mellitus

Overview

Diabetes mellitus (DM) is a group of metabolic disorders characterised by chronic hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Insulin, produced by pancreatic β-cells, plays a crucial role in regulating glucose uptake, utilisation, and storage. Disturbance in this mechanism leads to elevated blood glucose levels and subsequent metabolic derangements in carbohydrate, fat, and protein metabolism.

The two major categories are Type 1 diabetes mellitus (T1DM) — an autoimmune β-cell destruction leading to absolute insulin deficiency — and Type 2 diabetes mellitus (T2DM) — characterised by peripheral insulin resistance combined with inadequate compensatory insulin secretion. Other specific types include Secondary diabetes (due to pancreatic diseases, endocrinopathies, or drugs) and Gestational diabetes.

Uncontrolled diabetes results in acute complications such as Diabetic ketoacidosis (DKA) and Hyperosmolar hyperglycaemic state (HHS), as well as chronic vascular complications affecting eyes, kidneys, nerves, and cardiovascular system. Effective management integrates lifestyle modification, pharmacologic therapy, and continuous monitoring to prevent or delay complications.

Epidemiology

Diabetes mellitus is one of the most prevalent chronic diseases globally. According to the International Diabetes Federation (IDF) 2023, approximately 537 million adults (aged 20–79 years) are living with diabetes, and this number is expected to reach 643 million by 2030. Type 2 diabetes accounts for over 90% of cases worldwide.

The prevalence increases with age, obesity, and sedentary lifestyle. Men and women are affected equally, though men tend to develop diabetes earlier due to higher visceral fat accumulation. Urbanisation, dietary changes, and physical inactivity are major contributing factors, particularly in developing countries.

Type 1 diabetes is less common, representing about 5–10% of all diabetes cases, with peak incidence in childhood and adolescence. Gestational diabetes affects approximately 7–10% of pregnancies globally and poses a significant risk for later development of T2DM in both mother and child.

Pathophysiology

Clinical Presentation

The presentation of diabetes varies with disease type and stage. Type 1 diabetes often presents acutely, whereas Type 2 diabetes may remain asymptomatic for years before diagnosis.

Sign & Symptom	Pathogenesis	Frequency	Specificity
Polyuria	Osmotic diuresis from glucosuria	++++	+++
Polydipsia	Dehydration and increased plasma osmolality	++++	+++
Polyphagia with weight loss	Cellular glucose deprivation and increased catabolism	+++	++
Blurred vision	Osmotic swelling of lens due to hyperglycaemia	++	++
Fatigue / weakness	Energy deficit from poor glucose utilisation	+++	++
Recurrent infection (skin, UTI, candidiasis)	Impaired neutrophil and macrophage function	++	++

Investigation

Laboratory investigation confirms the diagnosis, identifies complications, and monitors treatment response. The key investigations include blood glucose levels, HbA1c, and screening for organ damage.

Diagnosis Criteria (Dx)

According to the American Diabetes Association (ADA, 2024), diabetes mellitus can be diagnosed if any of the following criteria are met, confirmed on repeat testing:

• Fasting Plasma Glucose (FPG): ≥126 mg/dL (7.0 mmol/L) after ≥8 hours fasting.
• 2-hour Plasma Glucose (OGTT): ≥200 mg/dL (11.1 mmol/L) during a 75 g glucose tolerance test.
• HbA1c: ≥6.5% using a standardised laboratory method (NGSP certified).
• Random Plasma Glucose: ≥200 mg/dL with classic symptoms of hyperglycaemia or hyperglycaemic crisis.

Prediabetes is defined by FPG 100–125 mg/dL, 2-hour OGTT 140–199 mg/dL, or HbA1c 5.7–6.4%. Accurate diagnosis allows for early intervention and prevention of long-term complications.

Complication

Diabetes mellitus (DM) leads to a wide range of acute and chronic complications due to prolonged hyperglycaemia and associated metabolic disturbances. The complications can be broadly categorised into acute metabolic derangements and chronic vascular complications. The chronic complications are further divided into microvascular (involving small vessels: retina, kidney, nerves) and macrovascular (large arteries: coronary, cerebral, peripheral). These pathophysiological processes share common mechanisms, including oxidative stress, formation of advanced glycation end-products (AGEs), endothelial dysfunction, inflammation, and impaired nitric oxide bioavailability.

Persistent hyperglycaemia alters both cellular metabolism and vascular structure. At the cellular level, excess glucose activates alternative metabolic pathways (polyol, hexosamine, and PKC pathways), resulting in reactive oxygen species (ROS) accumulation and cellular injury. Vascular dysfunction leads to ischaemia, tissue hypoxia, and progressive organ failure. The severity of complications correlates directly with the duration of diabetes and degree of glycaemic control (HbA1c level). Intensive glucose management, blood pressure control, and lipid optimisation are essential in preventing or delaying these complications.

Complication	Pathogenesis / Mechanism	Frequency	Clinical Manifestation / Notes
Diabetic Ketoacidosis (DKA)	Absolute insulin deficiency causes unrestrained lipolysis, leading to excessive ketone production and metabolic acidosis.	+++ (common in Type 1 DM)	Rapid-onset polyuria, vomiting, Kussmaul respiration, fruity breath; requires IV insulin and fluid replacement.
Hyperosmolar Hyperglycaemic State (HHS)	Relative insulin deficiency with severe hyperglycaemia causes dehydration and increased plasma osmolality without significant ketosis.	++ (older adults with Type 2 DM)	Extreme hyperglycaemia, altered mental status, severe dehydration; mortality higher than DKA.
Hypoglycaemia	Excess insulin or skipped meals cause low plasma glucose and neuroglycopenic symptoms.	+++ (especially with insulin or sulfonylureas)	Sweating, tremor, confusion, seizures; severe cases may lead to coma or death if untreated.
Diabetic Retinopathy	Chronic hyperglycaemia causes microaneurysm formation, pericyte loss, and retinal capillary leakage; advanced cases develop neovascularisation.	++++ (most common microvascular complication)	Blurry vision, floaters, retinal haemorrhage, risk of blindness; classified as non-proliferative or proliferative retinopathy.
Diabetic Nephropathy	Glomerular basement membrane thickening, mesangial expansion, and podocyte loss lead to proteinuria and renal failure.	+++ (30–40% of long-term DM)	Microalbuminuria progressing to macroalbuminuria and chronic kidney disease; major cause of end-stage renal disease (ESRD).
Diabetic Neuropathy	Hyperglycaemia-induced oxidative stress and sorbitol accumulation damage peripheral nerves; microangiopathy reduces blood flow to vasa nervorum.	++++	Distal symmetric polyneuropathy (glove-and-stocking distribution), autonomic neuropathy, and focal mononeuropathy.
Diabetic Foot Ulcer	Combination of neuropathy (loss of sensation), peripheral arterial disease, and poor wound healing leads to ulceration and infection.	+++	Chronic non-healing ulcers, risk of osteomyelitis, and amputation; requires offloading and infection control.
Coronary Artery Disease (CAD)	Accelerated atherosclerosis due to dyslipidaemia, endothelial dysfunction, and chronic inflammation.	++++	Stable angina, myocardial infarction, heart failure; leading cause of mortality in diabetes.
Cerebrovascular Disease	Endothelial damage and thrombosis in cerebral vessels cause ischaemic or haemorrhagic stroke.	+++	Transient ischaemic attack, stroke, cognitive decline; risk doubles in diabetic patients.
Peripheral Arterial Disease (PAD)	Atherosclerosis of lower limb arteries causing chronic ischaemia and impaired wound healing.	++	Intermittent claudication, rest pain, gangrene; major contributor to diabetic foot complications.
Diabetic Cardiomyopathy	Myocardial fibrosis and impaired calcium handling lead to diastolic and systolic dysfunction independent of CAD.	++	Heart failure with preserved or reduced ejection fraction; increased mortality in Type 2 DM.
Infection Susceptibility	Impaired neutrophil function, reduced chemotaxis, and vascular insufficiency.	+++	Recurrent urinary tract infections, skin abscesses, candidiasis, mucormycosis; poor wound healing.
Dermatologic Manifestations	Microangiopathy and glycation of dermal collagen.	++	Diabetic dermopathy, necrobiosis lipoidica, acanthosis nigricans, and fungal infections.
Oral and Dental Complications	Hyperglycaemia fosters bacterial growth and vascular fragility in gingival tissue.	++	Periodontitis, tooth loss, delayed healing post dental procedures.
Gestational Diabetes Complications	Maternal hyperglycaemia leads to foetal hyperinsulinaemia and macrosomia.	++ (5–10% of pregnancies)	Pre-eclampsia, polyhydramnios, neonatal hypoglycaemia, and long-term risk of T2DM in mother and child.
Diabetic Macular Oedema	Breakdown of blood-retinal barrier causes vascular leakage and fluid accumulation in macula.	++	Central vision loss; treatable with anti-VEGF therapy or laser photocoagulation.
Autonomic Neuropathy	Degeneration of autonomic fibres due to chronic hyperglycaemia and ischaemia.	++	Resting tachycardia, orthostatic hypotension, gastroparesis, erectile dysfunction, bladder atony.
Summary	Chronic metabolic stress damages endothelium and nerves via oxidative and inflammatory pathways.	++++	Effective glycaemic control, blood pressure management, and lifestyle modification reduce complication risk.

Treatment

The management of Diabetes Mellitus (DM) aims to achieve optimal glycaemic control, prevent acute and chronic complications, and improve quality of life. Treatment strategies are tailored according to diabetes type, comorbidities, and individual patient factors. For Type 1 DM, insulin replacement therapy remains the cornerstone, as endogenous insulin production is absent. A basal–bolus regimen or continuous subcutaneous insulin infusion (CSII) mimics physiological insulin secretion. For Type 2 DM, lifestyle modification and pharmacological agents are used to enhance insulin sensitivity or secretion.

Lifestyle modification forms the foundation of therapy. Patients should adopt a balanced diet rich in complex carbohydrates, fibre, and unsaturated fats while avoiding excessive sugar and trans fats. Regular aerobic and resistance exercise improves insulin sensitivity and cardiovascular health. Weight loss of even 5–10% can significantly improve glycaemic control. Pharmacologic therapy is initiated when lifestyle modification alone fails to maintain HbA1c below target levels (usually <7%).

Modern diabetes management involves a multifactorial approach — targeting not only glucose but also blood pressure and lipid levels to reduce cardiovascular risk. Periodic screening for complications, patient education, and adherence monitoring are essential components of long-term management.

Pharmacology

Pharmacologic treatment for diabetes focuses on achieving and maintaining normoglycaemia by enhancing insulin action, stimulating insulin secretion, or reducing hepatic glucose production. Therapeutic options are broadly classified into insulin therapy and non-insulin antihyperglycaemic agents.

1. Insulin Therapy

Insulin is essential in Type 1 DM and sometimes required in Type 2 DM with β-cell exhaustion. Types of insulin include rapid-acting (Lispro, Aspart), short-acting (Regular), intermediate (NPH), and long-acting analogues (Glargine, Detemir, Degludec). The typical total daily dose ranges from 0.4–1.0 units/kg/day, divided between basal and bolus doses. Insulin therapy reduces microvascular complications and allows flexible glycaemic control when combined with self-monitoring.

2. Oral Antihyperglycaemic Agents

Drug Class	Mechanism of Action	Example	Key Adverse Effects
Biguanides	Reduce hepatic gluconeogenesis and improve insulin sensitivity	Metformin	GI upset, lactic acidosis (avoid in renal impairment)
Sulfonylureas	Stimulate pancreatic insulin release by closing KATP channels	Glipizide, Glyburide	Hypoglycaemia, weight gain
DPP-4 inhibitors	Increase incretin (GLP-1, GIP) activity prolonging insulin secretion	Sitagliptin, Linagliptin	Nasopharyngitis, rare pancreatitis
SGLT2 inhibitors	Inhibit renal glucose reabsorption in proximal tubule	Empagliflozin, Dapagliflozin	Genital infections, dehydration, euglycaemic ketoacidosis
GLP-1 receptor agonists	Enhance insulin secretion, suppress glucagon, delay gastric emptying	Liraglutide, Semaglutide	Nausea, weight loss, rare pancreatitis
Thiazolidinediones (TZDs)	Increase insulin sensitivity via PPAR-γ activation	Pioglitazone	Weight gain, oedema, heart failure risk

3. Combination Therapy

In Type 2 DM, combination therapy is often required for adequate glycaemic control. Metformin is typically the first-line agent unless contraindicated, followed by an add-on from another class based on patient comorbidities, such as SGLT2 inhibitors or GLP-1 agonists for cardiovascular benefit.

Guideline

The management of Diabetes Mellitus (DM) should be comprehensive and individualised, addressing both glycaemic control and associated cardiovascular risk factors. According to the American Diabetes Association (ADA, 2024) and the World Health Organization (WHO, 2023), the primary objectives are to achieve and maintain glycaemic targets, prevent acute complications, and minimise long-term vascular damage.

The recommended glycaemic goals for most adults are: HbA1c <7%, fasting plasma glucose (FPG) 80–130 mg/dL, and postprandial glucose (PPG) <180 mg/dL. Targets may be relaxed (e.g., HbA1c <8%) in elderly or comorbid patients to reduce hypoglycaemia risk.

1. Non-pharmacologic Management

• Medical Nutrition Therapy (MNT): Emphasise carbohydrate counting, low-glycaemic index foods, fibre-rich diet, and caloric control. Reduce saturated fats <10% of total calories.
• Physical Activity: At least 150 minutes/week of moderate-intensity aerobic activity plus resistance training twice weekly.
• Weight Reduction: Target 5–10% weight loss in overweight or obese patients; BMI goal <25 kg/m².
• Smoking Cessation: Essential to reduce cardiovascular risk and improve microvascular outcomes.

2. Pharmacologic Management

Treatment selection depends on diabetes type, comorbidities, age, renal function, and cardiovascular status. Medication doses below are standard for adult patients of average weight and renal function.

• First-line (Type 2 DM): Metformin 500–2000 mg/day PO in divided doses, titrated as tolerated. Contraindicated if eGFR <30 mL/min/1.73m².
• Second-line:
  • SGLT2 inhibitors: Empagliflozin 10–25 mg/day PO; cardiovascular and renal protective benefits.
  • GLP-1 receptor agonists: Liraglutide 0.6–1.8 mg SC daily or Semaglutide 0.25–1 mg weekly; promotes weight loss.
  • DPP-4 inhibitors: Sitagliptin 100 mg/day PO; safe in renal impairment (dose adjust).
• Insulin Therapy: Initiate if HbA1c ≥10%, or in symptomatic hyperglycaemia. Start with basal insulin (Glargine 10 units at bedtime or 0.2 units/kg/day) and titrate to fasting glucose target.
• Combination therapy: If targets unmet after 3–6 months, combine Metformin with SGLT2 inhibitor, GLP-1 RA, or basal insulin.

3. Cardiovascular and Renal Risk Management

• Blood Pressure Control: Target <130/80 mmHg. Preferred agents: ACE inhibitors or ARBs (e.g., Lisinopril 10–40 mg/day).
• Lipid Control: Statins for all adults ≥40 years or with CVD risk; Atorvastatin 20–40 mg/day recommended.
• Antiplatelet Therapy: Aspirin 75–162 mg/day for secondary prevention of cardiovascular events.
• Renal Protection: Annual microalbuminuria screening; initiate ACEI/ARB if albuminuria >30 mg/g creatinine.

4. Monitoring and Follow-up

• HbA1c: Every 3 months if uncontrolled; every 6 months if stable.
• Self-Monitoring of Blood Glucose (SMBG): At least before meals and at bedtime for insulin users.
• Annual Screening: Eye examination, renal function (eGFR, albuminuria), foot exam, and lipid profile.

5. Individualised Care

Treatment must be tailored to patient preferences, comorbidities, and access to care. Patient education, self-management support, and psychological care are crucial. Shared decision-making between clinician and patient improves adherence and long-term success.

Example Doctor’s Orders

Disclaimer: Example for educational purposes only, not for direct patient advice.

Prognosis

With strict glycaemic control, most patients with diabetes can achieve normal life expectancy and reduce complication risk. The UKPDS and DCCT trials demonstrate that maintaining HbA1c <7% significantly decreases the incidence of microvascular complications. However, persistent poor control leads to progressive organ damage. Type 1 diabetes requires lifelong insulin, while Type 2 may remain controlled with oral therapy for years before needing insulin. Regular monitoring, patient education, and management of comorbidities are essential for optimal outcomes.

Prevention

Type 1 DM prevention remains limited; however, delaying onset is under research using immunomodulators. Type 2 DM is largely preventable through lifestyle modification — healthy diet, regular exercise (≥150 minutes/week), weight reduction, and avoidance of smoking. Early screening in high-risk individuals (family history, obesity, gestational diabetes) and treatment of prediabetes (Metformin 850 mg PO bid) can prevent progression. Public health interventions focusing on education and nutrition are crucial in reducing global diabetes prevalence.

Conclusion

Quiz (USMLE OSCE)

Frequently Asked Questions (FAQ)

What is the best first-line treatment for Type 2 Diabetes Mellitus?

Metformin remains the gold-standard first-line therapy due to its effectiveness, safety, low cost, and cardiovascular benefits. It improves insulin sensitivity, reduces hepatic glucose production, and does not cause hypoglycaemia. If contraindicated or not tolerated, SGLT2 inhibitors or GLP-1 receptor agonists can be used as alternatives.

When should insulin therapy be initiated in Type 2 DM?

Insulin should be started if HbA1c ≥10%, fasting glucose >250 mg/dL, or if the patient presents with symptoms of hyperglycaemia or catabolism (weight loss, ketonuria). Basal insulin (e.g., Glargine 10 units at bedtime) is typically initiated and titrated gradually. Insulin can be combined with oral agents for flexible control.

How often should diabetic patients have follow-up visits?

Most patients should be reviewed every 3 months until glycaemic targets are achieved. Once stable, follow-up every 6 months is appropriate. At each visit, review medication adherence, hypoglycaemic episodes, diet, exercise, and foot health. Annual screening for eye, kidney, and cardiovascular complications is essential.

Can diabetes be reversed or cured?

Type 1 DM cannot be cured due to autoimmune β-cell destruction. In contrast, Type 2 DM remission is possible through significant weight loss, lifestyle modification, or bariatric surgery. However, relapse is common if lifestyle changes are not maintained, so long-term follow-up remains crucial.

What are the long-term goals in diabetes management?

The ultimate goals are to prevent complications, maintain quality of life, and prolong survival. This includes strict glycaemic control, management of blood pressure and lipids, and lifestyle modification. Patient education and continuous monitoring are key to sustainable success.