Diabetes mellitus (DM) and tuberculosis (TB) are closely linked diseases that adversely affect each other's clinical course and treatment outcomes. Diabetes increases the risk of developing active tuberculosis by impairing both innate and adaptive immune responses, while tuberculosis worsens glycaemic control through systemic inflammation, stress-induced hyperglycaemia, and interactions between anti-tuberculosis and antidiabetic medications.

People with diabetes have approximately two to three times greater risk of developing active tuberculosis than the general population. Coexisting diabetes is associated with delayed sputum conversion, increased treatment failure, recurrent tuberculosis, multidrug-resistant tuberculosis (MDR-TB), higher mortality, and more frequent metabolic emergencies such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS). Early bidirectional screening and integrated management are essential for improving outcomes.

Pathophysiology

Diabetes impairs host immunity by reducing neutrophil function, macrophage activation, cytokine production, and T-cell-mediated immune responses, thereby increasing susceptibility to infection with Mycobacterium tuberculosis and reducing the ability to contain latent infection. Chronic hyperglycaemia also compromises pulmonary microvascular circulation and tissue repair, contributing to more severe pulmonary disease.

Tuberculosis itself induces systemic inflammation and increases secretion of stress hormones such as cortisol and catecholamines, resulting in increased insulin resistance and hepatic glucose production. In addition, antituberculosis medicines such as rifampicin and isoniazid interfere with glucose metabolism and the effectiveness of antidiabetic medications, making glycaemic control more difficult during TB treatment.

Risk factors

Diabetes-related risk factors

• Poor glycaemic control

• Long-standing diabetes mellitus

• Obesity

• Chronic kidney disease

• Malnutrition

• Smoking

• Excessive alcohol consumption

• Advanced age

Tuberculosis-related risk factors

• Previous tuberculosis

• Close contact with infectious TB patients

• Living in TB-endemic areas

• HIV infection

• Immunosuppression

• Corticosteroid therapy

• Low socioeconomic status

• Overcrowded living conditions

Clinical presentation

Patients may present with symptoms of one or both diseases.

Symptoms of tuberculosis

• Persistent cough for more than two weeks

• Fever

• Night sweats

• Weight loss

• Loss of appetite

• Fatigue

• Haemoptysis

Symptoms of worsening diabetes

• Polyuria

• Polydipsia

• Polyphagia

• Blurred vision

• Fatigue

• Persistent hyperglycaemia

• Recurrent infections

Atypical features

Patients with diabetes may present with:

• Delayed sputum conversion

• Lower lobe pulmonary infiltrates

• Extensive cavitary disease

• Minimal respiratory symptoms despite advanced disease

• Hyperosmolar hyperglycaemic state

• Diabetic ketoacidosis precipitated by tuberculosis

Diagnosis

Tuberculosis screening

People attending diabetes clinics should be screened for tuberculosis if they present with symptoms suggestive of TB.

Screening includes:

• Symptom screening

• Sputum smear microscopy

• GeneXpert MTB/RIF

• Chest radiography

• TB culture when indicated

Diabetes screening

People attending tuberculosis clinics should be screened for diabetes mellitus.

Diagnosis follows standard diabetes criteria:

• Fasting plasma glucose ≥7.0 mmol/L

• Random plasma glucose ≥11.1 mmol/L with symptoms

• HbA1c ≥6.5%

• Two-hour plasma glucose ≥11.1 mmol/L following a 75 g oral glucose tolerance test

Investigations

Tuberculosis assessment

• Sputum smear microscopy

• GeneXpert MTB/RIF

• Mycobacterial culture where available

• Chest X-ray

• Full blood count

Diabetes assessment

• Fasting plasma glucose

• Random blood glucose

• HbA1c

• Urine ketones when indicated

• Renal function tests

Monitoring during treatment

• Blood glucose monitoring

• Body weight

• Liver function tests

• Renal function tests

• Sputum examination according to TB treatment protocol

Management

General principles

Patients with both diabetes and tuberculosis should receive treatment for both conditions simultaneously.

Management should aim to:

• Achieve optimal glycaemic control

• Ensure adherence to anti-tuberculosis therapy

• Prevent drug interactions and adverse effects

• Reduce cardiovascular risk factors

• Monitor treatment response closely

Non-pharmacological management

Patients should be advised to:

• Maintain good blood glucose control

• Consume a balanced, nutritious diet with adequate calories and protein

• Maintain an ideal body weight

• Engage in regular physical activity as tolerated

• Stop smoking

• Avoid excessive alcohol consumption

• Reduce chronic stress

• Obtain adequate sleep

• Attend regular follow-up appointments

Pharmacological management

Tuberculosis treatment

Treat tuberculosis according to national tuberculosis treatment guidelines using the recommended anti-tuberculosis regimen.

Diabetes treatment during tuberculosis

Insulin

Insulin is the preferred glucose-lowering therapy for patients with active tuberculosis because it:

• Provides reliable glycaemic control

• Is not affected by rifampicin-induced hepatic enzyme induction

• Is effective during severe insulin resistance

• Is appropriate in patients with marked weight loss

• Can be safely used when liver disease develops during tuberculosis treatment

Patients already receiving oral glucose-lowering medicines may require temporary or permanent conversion to insulin during active tuberculosis.

Oral glucose-lowering medicines

Oral antidiabetic medicines should be used cautiously.

Metformin

Metformin may not be appropriate in patients with:

• Significant hepatic dysfunction

• Severe weight loss

• Poor nutritional status

Sulphonylureas

Sulphonylureas may become less effective because:

• Rifampicin accelerates their metabolism.

• Isoniazid antagonizes their glucose-lowering effect.

• Severe insulin resistance during active tuberculosis reduces their effectiveness.

If glycaemic control deteriorates despite oral therapy, insulin should be initiated rather than repeatedly increasing oral medication doses.

Drug interaction considerations

Rifampicin

Rifampicin:

• Is a potent hepatic enzyme inducer.

• Accelerates metabolism of oral glucose-lowering medicines.

• Shortens the plasma half-life of sulphonylureas.

• May reduce the effectiveness of oral antidiabetic therapy.

Patients may require adjustment of diabetes treatment during rifampicin therapy.

Isoniazid

Isoniazid:

• Antagonizes the action of sulphonylureas.

• Impairs insulin secretion.

• Reduces insulin sensitivity.

• Increases insulin and oral medication requirements.

Monitoring

Patients should undergo regular assessment of:

• Blood glucose

• HbA1c where appropriate

• Body weight

• Liver function

• Renal function

• Tuberculosis treatment response

• Sputum conversion according to national TB guidelines

Patients receiving insulin should also be monitored for hypoglycaemia as clinical improvement and nutritional status improve.

Prevention

Preventive measures include:

• Bidirectional screening:

  • Screen all tuberculosis patients for diabetes.

  • Screen diabetic patients for tuberculosis when TB symptoms are present.

• Achieve and maintain good glycaemic control.

• Promote healthy nutrition.

• Encourage regular physical activity.

• Maintain a healthy body weight.

• Ensure adequate sleep.

• Reduce chronic stress.

• Encourage smoking cessation.

• Limit alcohol intake.

• Promote adherence to tuberculosis treatment and diabetes management.

• Regular follow-up to detect complications early.

Outcome

Early diagnosis and integrated management of diabetes and tuberculosis significantly improve treatment outcomes. Good glycaemic control enhances immune function, promotes faster sputum conversion, reduces treatment failure, relapse, multidrug-resistant tuberculosis, and mortality. Patients managed with coordinated diabetes and tuberculosis care generally achieve better long-term metabolic and infectious disease outcomes than those receiving treatment for either condition alone.