Diabetes and Tuberculosis: an unholy alliance

Dr. Mohammad Tanvir IslamAssistant Professor, MedicineBangabandhu Sheikh Mujib Medical University

Dr. Shamim AhmedAssistant Professor, RespiratoryMedicineBangabandhu Sheikh Mujib Medical University

Background Epidemiology 347 million people worldwide have

diabetes 80% diabetes deaths in low- and

middle-income countries 7th leading cause of death in 2030 In Bangladesh between 2% and 21%

Diabetes 2013

Projected prevalence of DM in 2030

Tuberculosis around the world

About 9 million people around the world

A total of 1.5 million people died in 2013

The incidence of TB in Bangladesh is 225 per 100,000

Worldwide Tuberculosis

High burden TB countries

ChinaIndiaBrazilBangladeshIndonesiaPakistanRussia

Intersecting Epidemics

Big concern about twin epidemics Low to middle income countries DM increases the risk of TB 3 fold TB causes glucose intolerance

Association between diabetes and active tuberculosis in studies stratifying by glucose control

14.8% of PTB & 20.2% smear positive PTB cases are directly linked to DM

TB causes glucose intolerance 50 % of which normalizes after ATT

DM increases risk of TB 3 times TB increases risk of DM 2 times

Historical aspects

Since ancient times Susruta in 600 AD Avicenna (780-1027 AD) Roots 1950 Nicholas 1957 McCornick 2007

Pathogenesis of tuberculosis

Four possible outcomes: Immediate clearance of the organism Latent infection The onset of active disease (primary

disease) Active disease many years later

(reactivation disease).

Persons with medical conditions that weaken the immune system

HIV infection Diabetes mellitus Medical treatments such as

corticosteroids or organ transplant Substance abuse Organ transplants Malignancy

Pathophysiology Hyperglycemia favours growth , viability and

propagation of tubercle bacilli and hamper resistance to infection & repair capacity

Increased availability of glycerol and nitrogenous substances aid the growth of tubercle bacilli

High level of insulin have been shown to promote a decrease in Th1 immunity through a reduction in the Th1 cell to Th2 cell ration and interferon gamma to IL-4 ratio

Immunologic abnormalities in Diabetes

Abnormal chemotaxis Decreased peripheral monocytes

with impaired phagocytosis Poor blast transformation of

lymphocytes Defective C3 opsonic function Decrease in Th1 immunity

Pulmonary physiologic dysfunction in diabetes

Diminished bronchial reactivity Reduced diffusion capacity Occult mucous plugging of airways Reduced ventilatory response to

hypoxaemia

Pathophysiologic dysfunction of lung in diabetes

Microangiopathic change in pulmonary vasculature

Non-enzymatic glycosylation of tissue protein

Thickening of epithelial and caplillary BM

Interference with clearance mechanism

Increased risk of

tuberculosis

Diabetes

Neutrophil• Abnormal

Chemotaxis• Phagocytosis• Microbicidal acitvity

Reduction in Th1 cells

Interferon gamma

Increased availability of Glycerol and nitrogenous substances

Lung physiological and pathological

dysfunction

Increased risk of Tuberculosis

Impairment ofInnate immunity Acquired immunity

DiabetesLung Physiologic dysfunction

Lung Pathologic dysfunction

Impact of TB on glycaemic status

Relative and absolute overproduction of adrenocorticotropic hormone

Increased supply of corticosteroids Corticosteroids are insulin

antagonists resulting in insulin resistant diabetes.

Clinical menifastations

More aggressive course Less clinical manifestations Typical features like cough, weight

loss are less prominent Prolonged duration of fever

Clinical menifastations

Features of one disease can mimic the other

Might progress rapidly Flare up or spread of tuberculosis More complications Risk for Drug-resistant TB

Comparison of clinical features

Clinical feature

DM & TB TB only

Fever 64% 98%Night sweat 52% 85%Cough>3wks 71% 96%Weight loss 69% 94%

Hossain D, Latif ZA, Mahtab H Clinical and radiological presentation of pulmonary Tuberculosis in diabetic and non-diabetic patients. J Soc Heart Chest Dis 2004;2:69-72

Radiology of PTB in DM

Frequently atypical Lower lobe opacity Multilobar Cavitary lesion Pleural effusion

Comparison of radiological features in TB patients with or without DM

Radiological feature

DM +TB TB alone

Upper lobe opacity 17% 56%Lower lobe opacity 19% 7%Multi lobe opacity 64% 36%Cavity 82% 59%

C.Perez et.al. 2001

Radiology

Summery

DM & TB prevalence is increasing They are epidemic in identical areas DM is a risk factor for TB TB causes glucose intolerance Clinical and radiological features in a

diabetic TB patient may be atypical