This document discusses the relationship between asthma and diabetes. It notes that both are immune-mediated chronic inflammatory diseases believed to be divergent due to opposing Th1 and Th2 responses. However, altered environmental factors are associated with a growing prevalence of both diseases occurring together. The loss of traditional immune regulators is thought to disrupt the Th1/Th2 paradigm, increasing risk of both allergy and autoimmunity. Immune deficiencies are a major cause of the co-occurrence of asthma and autoimmune diseases like type 1 diabetes. The document also examines links between type 2 diabetes and asthma, as well as interactions between drugs used to treat the conditions.

1. Asthma & diabetesAsthma & diabetes
Fawzia Abo Ali
Prof. of allergy and immunology

2. Asthma and type 1 diabetes mellitus (T1DM)
• Both are immune mediated chronic inflammatory
diseases
• Asthma is a T helper type 2(Th2)-dominant
disease.
• (T1DM), is Th1-dominant disease.
• A negative association has been suggested
between type 1 diabetes and asthma, supporting
the Th1/Th2 paradigm.
TH1
TH2

3. Autoimmune diseases
Type 1 diabetes Allergy asthma
Asthma and Diabetes Don’t MixAsthma and Diabetes Don’t Mix

4. Frequency of Type 1 diabetes
worldwide
In the last decades, an increase in bronchial asthma and
type 1 diabetes occurrence has been observed with
positive association in affluent countries.

5. • The geographical map of immune disease frequency is
the mirror image of that for infectious & parasitic disease
distribution..
,
,

7. Coexistences of asthma & type 1 diabetes
the hygiene hypothesis

8. • when environmental stimulation is
reduced, and where genetic
predisposition exists, a dysfunctional
Th2 bias will persist and predispose
to atopic disorders.
• A failure of immune regulation
associated with loss of the traditional
educators of the immune system
could thus result in a parallel
increase in immune deviation at both
ends of the Th1/Th2 spectrum .

9. • The development of strong immune responses
against antigens from infectious agents could
inhibit responses to ‘weak’ antigens such as
autoantigens and allergens.
• Antigen competion for cytokines necessary for
immune balance
• Some of the molecules known to play an important
role are IL-2, IL-7, and IL-15.
• development of non-Th2 asthma due to infection-
related elements, genetics and oxidative stress, and
the development of neutrophilic inflammation.

10. 2. Selective IgA deficiency (sIgAD)
• It has been postulated that secretory IgA plays a
protective role against allergic disorders as well
by eliminating allergens at the mucosal level.
• Autoimmune disorders including type 1 diabetes
mellitus (T1DM) occur more frequently in
patients with sIgAD, with an estimated
prevalence of 7%– 36% .
• Loss of protective iga allow external and internal
antigen to invade the host

12. Asthma in Type 2 diabetes
• Asthma is common in Type 2 diabetic patients,
especially in those with higher BMI, that is
related to high insulin resistance.
• Dt 2 play probably an important role in
worsening of lung function in patients with co-
existence of BA .
• Obese people with asthma tend to have more
symptoms, more frequent exacerbations,
lower quality of life, and decreased response
to asthma medications.

13. • Independent of obesity, subjects with
diabetes may be at higher risk of asthma.
Similarly, insulin resistance and the
metabolic syndrome have been associated
to lower lung function
• insulin resistance may be involved in the
airway smooth muscle hypercontractility .
• Patients with type 2 diabetes had
significantly lower spirometric
values for the same patients .

14. Type 2 diabetes in asthma
• Patients with pre-existing asthma have a higher risk of
developing subsequent type 2 diabetes than those
without.
• Possible mechanisms include:
• genetic pleiotropy
• lung-related inflammatory cytokines and their effects on
insulin sensitivity,
• direct effects of hypoxia on glucose metabolism.
• Obesity is a major risk factor for diabetes, and it is also
associated with higher risk of asthma.
• Steroids and antiasthma drugs

15. Drug interplay
• Therapies targeting insulin resistance may
benefit obese asthmatic adults with insulin
resistance.
• insulin sensitisers ,such as biguanides (like
metformin) and pioglitazone, could be
preferentially used in obese, insulin-resistant,
asthmatic.

16. • Metformin is an anti-diabetic drugs, included in the
activation of AMP-activated protein kinase (AMPK).
• It also attenuate allergic eosinophilic airway inflammation
and inhibit airway smooth muscle cell proliferation .
• Pioglitazone is one of the thiazolidinedione compounds
that have been used as antidiabetic drugs. Recent studies
have revealed that Pioglitazone have anti-inflamatory, &
can suppress the activation of macrophages and reduce
nitric oxide and inflammatory cytokines of asthma.

17. • An anti-asthma drug has shown "promising" outcomes in
reducing blood sugar levels in people with type 2
diabetes, according to a recent US study.
Amlexanox is an anti-inflammatory and anti-allergic drug,
which was developed in Japan in the 1980s and is now
commonly used to treat asthma. Previous research saw
the drug being tested on obese mice which caused them
to lose weight, while the animals' insulin
sensitivity increased.

18. • The effects of inhaled corticosteroid on
insulin sensitivity in asthmatic patients
• There are mixed data as to the effect of ICS
on glucose metabolism.
• The largest population-based study showed
an increased risk of development and
progression of diabetes among patients on
ICS therapy.
• Steroid-induced dysglycemia often presents
with post-meal and daytime hyperglycemia

19. Take home message
Asthma and type 1 diabetes mellitus are common
immune mediated chronic inflammatory diseases,
believed for long to be divergent due to th1 & th2
contrary.
Altered ecological factors is associated with fast growing
conjoint prevalence of both diseases.
Loss of traditional immune educators is responsible for
alteration of TH paradigm resulting in growing
prevalence of both allergy and autoimmune diseases.

20. Immune deficiency is a major cause of coexistence of
allergy and autoimmunity.
Type 2 diabetes and asthma are common association
due to mutual risk factors,they may share some drugs in
the near future.
An unanswered question remains about is it wise to
eradicate infections & keep the earth clean????? To
suffer allergy & autoimmunity.

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