Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Insulin, produced by the pancreatic β-cells of the pancreas, plays a central role in regulating glucose metabolism by facilitating glucose uptake into tissues and maintaining normal carbohydrate, fat, and protein metabolism. Deficiency of insulin, resistance to its action, or a combination of both leads to elevated blood glucose concentrations and widespread metabolic abnormalities.

Diabetes mellitus is a major global public health problem and one of the leading causes of morbidity and mortality. If left untreated or poorly controlled, it may result in acute metabolic emergencies as well as chronic complications affecting the eyes, kidneys, peripheral nerves, heart, brain, and blood vessels. Early diagnosis, appropriate treatment, regular follow-up, and effective risk factor modification significantly reduce complications and improve long-term outcomes.

Pathophysiology

The underlying mechanism of diabetes mellitus depends on the specific type of diabetes but ultimately results in chronic hyperglycaemia. In type 1 diabetes mellitus, autoimmune destruction of pancreatic β-cells causes absolute insulin deficiency. As insulin production declines, glucose cannot enter insulin-dependent tissues efficiently, resulting in increased hepatic glucose production, reduced peripheral glucose utilization, accelerated lipolysis, protein catabolism, and ketone body formation, which may lead to diabetic ketoacidosis.

Type 2 diabetes mellitus develops through a combination of insulin resistance and progressive β-cell dysfunction. Initially, insulin resistance in skeletal muscle, adipose tissue, and the liver impairs glucose uptake and increases hepatic glucose production. Pancreatic β-cells initially compensate by increasing insulin secretion; however, over time they become unable to maintain adequate insulin production, leading to persistent hyperglycaemia. Chronic hyperglycaemia promotes oxidative stress, endothelial dysfunction, inflammation, and formation of advanced glycation end-products (AGEs), resulting in progressive damage to blood vessels and multiple organs.

Classification

Diabetes mellitus is classified into four major categories.

Type 1 diabetes mellitus (T1DM)

An autoimmune disease characterized by destruction of pancreatic β-cells, resulting in absolute insulin deficiency. Lifelong insulin therapy is required.

Type 2 diabetes mellitus (T2DM)

Characterized by insulin resistance with progressive decline in pancreatic β-cell function. It accounts for approximately 90–95% of diabetes cases worldwide.

Gestational diabetes mellitus (GDM)

Diabetes first diagnosed during the second or third trimester of pregnancy that does not meet the diagnostic criteria for overt diabetes before pregnancy.

Specific types of diabetes

These include diabetes resulting from identifiable causes such as:

• Monogenic diabetes syndromes (e.g., maturity-onset diabetes of the young [MODY], neonatal diabetes)

• Diseases of the exocrine pancreas

• Endocrine disorders

• Drug- or chemical-induced diabetes (e.g., glucocorticoids, antiretroviral therapy)

• Genetic defects affecting insulin secretion or insulin action

Risk factors

The risk of developing diabetes mellitus increases with the presence of one or more of the following factors:

• Family history of diabetes mellitus

• Age 40 years or older

• Overweight or obesity

• Central obesity

• Physical inactivity

• Unhealthy diet

• Hypertension

• Dyslipidaemia

• History of cardiovascular disease

• Previous gestational diabetes mellitus

• Previous delivery of a baby weighing more than 4 kg

• Polycystic ovary syndrome

• Long-term corticosteroid or immunosuppressive therapy

• Impaired fasting glucose or impaired glucose tolerance

At-risk screening

Early diagnosis and treatment reduce the risk of complications and delay progression of the disease. Annual screening using fasting plasma glucose or HbA1c is recommended for:

• Adults aged 40 years and above

• Children and adults younger than 40 years who are overweight or obese and have at least two additional risk factors

• Individuals with impaired fasting glucose or impaired glucose tolerance

• Individuals with previous cardiovascular disease

• Patients receiving long-term corticosteroids or immunosuppressive therapy

• Women with previous gestational diabetes mellitus

• Women with polycystic ovary syndrome

• Pregnant women at the first antenatal visit if overweight, with previous gestational diabetes, previous macrosomic infant (>4 kg), previous stillbirth, or neonatal death

• All pregnant women during the second or third trimester for gestational diabetes screening

Clinical presentation

Clinical manifestations vary according to the severity and duration of hyperglycaemia.

Classical symptoms

• Polyuria

• Polydipsia

• Excessive thirst

• Polyphagia

• Unexplained weight loss

• Fatigue

• Blurred vision

Late manifestations

Some patients present only after complications have developed, including:

• Recurrent bacterial infections

• Recurrent fungal infections

• Pruritus vulvae

• Balanitis

• Peripheral neuropathy

• Paraesthesia

• Chronic non-healing ulcers

• Diabetic foot lesions

Diagnostic criteria

Diabetes mellitus (WHO 2006)

Diabetes mellitus is diagnosed if any one of the following criteria is met:

• Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL)

• Two-hour plasma glucose ≥11.1 mmol/L (200 mg/dL) after a 75 g oral glucose tolerance test

• Random plasma glucose ≥11.1 mmol/L (200 mg/dL) in the presence of classical symptoms of hyperglycaemia

• HbA1c ≥6.5%

Gestational diabetes mellitus (WHO 2013)

Diagnosis is made when one of the following values is present after a 75 g oral glucose tolerance test:

• Fasting plasma glucose 5.1–6.9 mmol/L

• Two-hour plasma glucose 8.5–11.0 mmol/L

Values of fasting plasma glucose ≥7.0 mmol/L or two-hour plasma glucose ≥11.1 mmol/L indicate overt diabetes rather than gestational diabetes.

Investigations

Initial investigations

All patients with suspected or newly diagnosed diabetes should undergo:

• Fasting plasma glucose

• Random blood glucose

• HbA1c

• Oral glucose tolerance test when indicated

• Urinalysis

• Urine albumin or urine albumin-to-creatinine ratio

• Serum creatinine and estimated glomerular filtration rate

• Lipid profile

• Liver function tests when indicated

• Electrolytes when indicated

• Blood pressure measurement

• Weight, body mass index, and waist circumference

• Comprehensive foot examination

• Dilated retinal examination or fundoscopy

Impaired glucose tolerance

Impaired glucose tolerance and impaired fasting glucose are intermediate states between normal glucose regulation and diabetes mellitus. Individuals with these conditions have an increased risk of developing type 2 diabetes mellitus and cardiovascular disease.

Progression to diabetes may be reduced by:

• Dietary modification

• Regular physical activity

• Weight reduction

• Metformin therapy in selected high-risk individuals

General principles of management

Management of diabetes mellitus is lifelong and should be individualized according to the type of diabetes, age, comorbidities, risk of hypoglycaemia, and patient preferences.

The major components of management include:

• Lifestyle modification

• Nutritional therapy

• Regular physical activity

• Weight management

• Patient education

• Pharmacological therapy when indicated

• Regular monitoring of glycaemic control

• Prevention and management of complications

Detailed treatment recommendations are provided in the related articles:

• Glycaemic management of type 2 diabetes mellitus

• Insulin therapy in diabetes mellitus

• Self-monitoring of blood glucose in diabetes mellitus

• Clinical monitoring of people with diabetes mellitus

• Perioperative management of diabetes mellitus

Prevention

Primary prevention focuses on reducing modifiable risk factors, while secondary prevention aims to prevent complications in individuals with established diabetes.

Preventive measures include:

• Maintaining a healthy body weight

• Consuming a balanced diet rich in vegetables, fruits, legumes, and whole grains

• Limiting intake of refined carbohydrates and sugar-sweetened beverages

• Engaging in at least 150 minutes of moderate-intensity physical activity per week

• Avoiding tobacco use

• Limiting alcohol consumption

• Annual screening of high-risk individuals

• Early treatment of prediabetes where appropriate

• Optimal control of blood pressure and lipid levels

• Regular screening for diabetic complications

• Patient education and adherence to treatment

Outcome

The prognosis of diabetes mellitus depends largely on early diagnosis, sustained glycaemic control, management of cardiovascular risk factors, and adherence to treatment. Patients who achieve recommended glycaemic targets and receive regular monitoring have a substantially lower risk of developing microvascular and macrovascular complications and generally enjoy a good quality of life.

Poorly controlled diabetes is associated with progressive damage to the eyes, kidneys, peripheral nerves, heart, brain, and blood vessels, leading to retinopathy, nephropathy, neuropathy, diabetic foot disease, myocardial infarction, stroke, chronic kidney disease, disability, and premature death. Lifelong follow-up, multidisciplinary care, and patient education remain essential for improving long-term outcomes.

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Insulin, produced by the pancreatic β-cells of the pancreas, is essential for facilitating cellular glucose uptake and regulating carbohydrate, fat, and protein metabolism. When insulin production becomes insufficient or body tissues become resistant to its action, blood glucose levels rise, leading to metabolic disturbances and progressive damage to multiple organs.

Diabetes is one of the leading causes of morbidity and mortality worldwide and is associated with both acute metabolic emergencies and chronic microvascular and macrovascular complications. These include diabetic ketoacidosis, hyperosmolar hyperglycaemic state, cardiovascular disease, chronic kidney disease, diabetic retinopathy, peripheral neuropathy, diabetic foot disease, and stroke. Early diagnosis, lifestyle modification, appropriate pharmacological treatment, and regular monitoring significantly reduce complications and improve quality of life.

Pathophysiology

The pathophysiology of diabetes mellitus differs according to its type but ultimately results in chronic hyperglycaemia. In type 1 diabetes mellitus, autoimmune destruction of pancreatic β-cells leads to absolute insulin deficiency, preventing glucose from entering insulin-dependent tissues such as skeletal muscle and adipose tissue. Consequently, hepatic glucose production increases while peripheral glucose utilization decreases, resulting in marked hyperglycaemia. Fat breakdown accelerates, producing ketone bodies that may lead to diabetic ketoacidosis.

In type 2 diabetes mellitus, insulin resistance develops in skeletal muscle, adipose tissue, and the liver, causing impaired glucose uptake and increased hepatic glucose production. Initially, pancreatic β-cells compensate by producing larger amounts of insulin; however, progressive β-cell dysfunction eventually leads to inadequate insulin secretion. Persistent hyperglycaemia causes glucotoxicity, oxidative stress, inflammation, endothelial dysfunction, and the formation of advanced glycation end-products (AGEs), which damage blood vessels, nerves, kidneys, retina, and other tissues. Over time, these pathological changes result in the chronic complications of diabetes affecting multiple organ systems.

Classification

Diabetes mellitus is classified into:

Type 1 diabetes mellitus (T1DM)

Caused by autoimmune destruction of pancreatic β-cells resulting in absolute insulin deficiency.

Type 2 diabetes mellitus (T2DM)

Characterized by insulin resistance with progressive loss of pancreatic β-cell insulin secretion. It accounts for approximately 90–95% of all diabetes cases.

Gestational diabetes mellitus (GDM)

Hyperglycaemia first recognized during the second or third trimester of pregnancy that does not meet the criteria for overt diabetes before pregnancy.

Specific types of diabetes

Caused by identifiable conditions including:

• Monogenic diabetes syndromes (e.g., MODY, neonatal diabetes)

• Diseases of the exocrine pancreas

• Endocrine disorders

• Drug- or chemical-induced diabetes (e.g., glucocorticoids, antiretroviral drugs)

• Genetic defects affecting β-cell function or insulin action

Note: Maturity-onset diabetes of the young (MODY) commonly presents between 25 and 45 years of age and management varies depending on the genetic subtype.

Risk factors

Risk factors include:

• Family history of diabetes

• Age ≥40 years

• Overweight or obesity

• Central obesity

• Physical inactivity

• Unhealthy diet

• Hypertension

• Dyslipidaemia

• Previous gestational diabetes

• Polycystic ovary syndrome

• Previous baby weighing >4 kg

• History of cardiovascular disease

• Long-term corticosteroid or immunosuppressive therapy

• Impaired fasting glucose or impaired glucose tolerance

At-risk screening

Annual screening using fasting plasma glucose or HbA1c is recommended for:

• Adults aged ≥40 years

• Children and adults younger than 40 years who are overweight or obese with at least two additional risk factors

• Individuals with impaired fasting glucose or impaired glucose tolerance

• Individuals with previous cardiovascular events

• Patients receiving long-term corticosteroids or immunosuppressive therapy

• Women with previous gestational diabetes mellitus

• Women with polycystic ovary syndrome

• Pregnant women at their first antenatal visit if overweight or with previous GDM, previous macrosomic infant (>4 kg), previous stillbirth, or neonatal death

• All pregnant women during the second or third trimester for gestational diabetes screening

Clinical presentation

Classical symptoms

• Polyuria

• Polydipsia

• Excessive thirst

• Polyphagia

• Weight loss

• Fatigue

• Blurred vision

Late presentation

• Recurrent bacterial infections

• Recurrent fungal infections

• Pruritus vulvae

• Balanitis

• Paraesthesia

• Peripheral neuropathic pain

• Non-healing ulcers

• Diabetic foot lesions

Diagnostic criteria

Diabetes mellitus (WHO 2006)

Diagnosis is confirmed if one of the following is present:

• Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL)

• Two-hour plasma glucose ≥11.1 mmol/L (200 mg/dL) following a 75 g oral glucose tolerance test

• Random plasma glucose ≥11.1 mmol/L (200 mg/dL) in the presence of classical symptoms

• HbA1c ≥6.5%

Gestational diabetes mellitus (WHO 2013)

• Fasting plasma glucose 5.1–6.9 mmol/L

• Two-hour plasma glucose 8.5–11.0 mmol/L after a 75 g oral glucose load

Overt diabetes in pregnancy

• Fasting plasma glucose ≥7.0 mmol/L

• Two-hour plasma glucose ≥11.1 mmol/L

Investigations

Baseline investigations

• Fasting plasma glucose

• Random blood glucose

• HbA1c

• Oral glucose tolerance test (when indicated)

• Urinalysis

• Urine albumin or urine albumin-creatinine ratio

• Serum creatinine and eGFR

• Lipid profile

• Liver function tests

• Electrolytes

• Blood pressure measurement

• Weight, BMI, waist circumference

• Fundoscopy or retinal examination

• Comprehensive foot examination

Prevention

Prevention focuses on reducing modifiable risk factors and delaying disease progression.

Measures include:

• Maintaining a healthy body weight

• Consuming a balanced diet rich in vegetables, fruits, whole grains, and fibre

• Engaging in at least 150 minutes of moderate physical activity each week

• Avoiding tobacco use

• Limiting alcohol intake

• Annual screening of individuals at increased risk

• Early identification and treatment of prediabetes

• Regular monitoring and control of blood pressure and lipid levels

• Routine screening for diabetic eye disease, kidney disease, and foot complications

• Patient education on medication adherence, self-monitoring of blood glucose, and healthy lifestyle practices

Outcome

The prognosis of diabetes mellitus depends largely on the timing of diagnosis, the degree of glycaemic control, adherence to treatment, and the presence of complications. Patients who maintain good glycaemic control through lifestyle modification, regular monitoring, and appropriate pharmacological therapy have a substantially lower risk of developing microvascular and macrovascular complications and generally achieve a normal or near-normal life expectancy. Conversely, poorly controlled diabetes is associated with progressive damage to the kidneys, retina, peripheral nerves, heart, brain, and blood vessels, leading to chronic kidney disease, blindness, diabetic foot ulcers, amputations, myocardial infarction, stroke, recurrent infections, and premature death. Continuous follow-up, multidisciplinary care, patient education, and early management of cardiovascular risk factors are essential for improving long-term outcomes.