DIABETES

BY: Ezhuthachan Mithu Mohanan (MSIWM043)

Diabetes is a metabolic disorder characterized by hyperglycaemia which results in a lack of insulin secretion, insulin action, or both the conditions. Metabolic abnormalities are caused due to a low level of resistance to insulin. The effect of symptoms can be classified based on the type and duration of diabetes. Diabetes has also been associated with many metabolic disorders such as acromegaly and hypercortisolism for example insulin resistance has been observed in patients with acromegaly in the liver. Hypercortisolism (Cushing syndrome) produces visceral obesity, insulin resistance, dyslipidaemia which leads to hyperglycaemia and reduces glucose tolerance. Besides, diabetes been associated with metabolic disorders, clinical convergence between type 1 diabetes (T1D), and type 2 diabetes(T2D) is also observed. T2D patients develop a progressive decline in total beta-cell mass. Thus there are many interlinked complications due to diabetes.

According to the report by WHO 2019, 10 main issues demand attention one of them is noncommunicable diseases such as diabetes, cancer, and heart disease. These are collectively responsible for 70% of deaths worldwide. According to the National Health Portal, the Government of India, nearly 5.8 million deaths occur due to noncommunicable diseases in India (WHO 2015). As per data provided by Directorate General of Health Services Ministry of Health & Family Welfare, Government of India (MoHFW) 2016-2017, 2.24 core persons were screened for Common noncommunicable diseases like diabetes, hypertension, cardiovascular disorders, and common cancers. From this, 9.7 % was diagnosed to be diabetes, 12.09% was diagnosed to be hypertension, 0.55% was diagnosed to be cardiovascular disease and 0.17% was with common cancers.

Events occurred from discovery of Diabetes to development of various drugs 

YEAREVENTS
1552 BCHESY-RA documented urination as symptom of mysterious disease
133 ADAraetus of Cappodocia coined the word diabetes
1675Thomas Willis coined the word mellitus
1776Dobson confirmed presence of excess sugar in patients
1800Discovered chemical test for presence of sugar in urine
1700’s and 1800’sPhysician began to realize dietary changes help manage diabetes
1857Claude Bernard confirmed that the diabetes occur due to excess glucose production
1870’sDuring Franco Prussian war French physician Apollinaire Bouchardat proved that the diabetes patients symptoms improved due to war related food rationing
1889Oskar Minkowski and Joseph Von Mering extract obtained from dogs pancreas
Early 1900Development of oat cure, potato therapy, starvation diet.George Zuelzar injected pancreatic extract to control diabetes
1916Boston scientist Elliott Joslin wrote book “ The Treatment Of Diabetes Mellitus “
1922Frederick Banting discovered insulin to treat diabetes and won Nobel Prize in medicine 1923
1978Production of recombinant human DNA insulin
1996For the treatment of type 22 diabetes Thiazolidinediones (TZDs) were introduced.
2005The  amylin analogue known as pramlintide, which was approved by the FDA
2008Colesevelam approved for type 2 diabetes by FDA
2009Bromocriptine approved for diabetes
2013Canagliflozin  is the first SGLT- 2 inhibitor  approved by FDA  [Sodium Glucose Co-Transporter 2 Inhibitors], Dapagliflozin approved in 2014 by FDA

(Source: Saudi Med et al., 2002, John et al., 2014)

Diagnosis of Diabetes: 

There are several methods used for the diagnosis of Diabetes Mellitus. According to American Diabetes Association (ADA) the most standard diagnostic criteria is as follows 

  1. Hemoglobin A1c (HbA1c)
  2. Fasting Plasma Glucose (FPG)
  3. Oral Glucose Tolerance Test (OGTT)

 Hemoglobin A1c (HbA1c):

The average level of blood sugar over past two to three months can be diagnosed using hemoglobin A1c test. The main advantage of this type of diagnosis is that there is no need of fasting. A1c is measured using percentage The standard referred by ADA for normal person is less than 5.7%.

 Diagnosis of Diabetes by checking Hemoglobin A1c (HbA1c)


Hemoglobin A1c
NormalLess than 5.7%
Prediabetes 5.7% to 6.4%
Diabetes 6.5% higher

Fasting Plasma Glucose (FPG):

It is used to check fasting blood sugar levels. The patient should fast for 8 hours before the test. It is mainly done during morning. For normal person the FPG is lower than 100mg/dl.

Diagnosis of Diabetes by checking Fasting Plasma Glucose (FPG)

FPG
Normal100mg/dl or less
Pre diabetes100 mg/dl to 125 mg/dl
Diabetes 126 mg/dl or high

Oral Glucose Tolerance Test (OGTT)

This method is used to diagnose blood sugar level before and after 2 hours of a sweet drink. For normal person the OGTT is less than 140mg/dl

 Diagnosis of Diabetes by checking Oral Glucose Tolerance (OGTT)

OGTT
Normal140mg/dl or less
Pre diabetes 149 to 199mg/dl
Diabetes200 mg/dl or high

Overview of infections of respiratory tract and its pathogens

By: Shaily Sharma (MSIWM041)

  • A brief overview of the infections of the respiratory tract and its pathogens:

The respiratory tract along with the gastrointestinal tracts is one of the major connections between the interiors of the body and the outside environment.

The respiratory tract is the pathway is that pathway of the body through which fresh oxygen enters the body and removes the excess carbon dioxide which is not needed by the body. 

  • Anatomy of the respiratory system:
  • Broadly, the respiratory system of humans can broadly be divided into two distinct areas; the upper and the lower respiratory tracts.
  • The parts that consist the lower respiratory tract are:
  1. Trachea
  2. Bronchi, and
  3. Bronchioles
  • The respiratory pathway begins with the nasal and the oral passages. These passages serve to humidify the air that is inspired. These pathways extend past the nasopharynx and the oropharynx to the trachea and then to the lungs.
  • The trachea is the organ that divides into the bronchi, which then further subdivides into the bronchioles. The bronchioles are the smallest branches of the trachea which finally terminate into the alveoli.
  • Approximately 300 million alveoli are said to present in the lungs. These mainly serve as the primary, microscopic, gas exchange structures of the respiratory tract.

See the source image

  • The lungs (along with the respiratory system) and the heart lie in the thoracic cavity. 
  • The thoracic cavity has three partitions that are separated from one other by the pleura (the pleura majorly cushions the lungs and reduce the friction which may develop between the lungs, rib cage and the chest cavity. It is a two layered membrane covering the lungs.)
  • The lungs occupy the right and the left pleural cavity while the mediastinum (the space between the right and the left lungs) is occupied by the esophagus, trachea, large blood vessels along with the heart.
  • Pathogenesis of the respiratory tract:
  • The success of an organism to cause disease is mainly dependent on the organism’s ability to cause disease (pathogenesis), and
  • The human hosts ability to prevent the infection (strength of the host’s immune system)
  • The host factors that help in non-specifically protect the respiratory tract from infection are:
  1. Nasal hair
  2. Convoluted passages and the mucous lining of the nasal turbinate
  3. Secretory IgA and non-specific antibacterial substances (like lysozyme) in respiratory secretions
  4. The cilia and the mucous lining of the trachea and reflexes such as coughing and sneezing. 
  • In addition to the non-specific hosts defenses, normal flora of the nasopharynx and the oropharynx help in the prevention of colonization of the upper respiratory tract. 

Microorganism factors:

Organisms possess certain traits that promote colonization leading to infection in the host. The factors that influence the respiratory tract infections are –

  1. Adherence: 
  • The potential of a microorganism depends, in one way or the other, on its ability to establish a stable contact/foothold on the surface of the host by the process of adherence. 
  • The ability of microorganisms to adhere to the host surface is dependent on two factors:
  1. Presence of normal flora, and
  2. Overall state of the host.
  •  Surviving or growing on host tissue without causing harmful effects is called colonization. 
  • Most etiologic agents must first adhere to the mucosa of the respiratory tract to some extent before they can cause harm.
  • Example: Streptococcus pyogenes possess specific adherence factors and its gram-positive cell wall contains lipoteichoic acids and M proteins. Many gram-negative bacteria like Enterobacteriaceae, Pseudomonas spp., Bordetella pertussis, adhere by the means of proteinaceous fingerlike projections called fimbriae. 
  • Viruses possess either a hemagglutinin or other proteins that mediate that epithelial attachment.
  1. Toxins
  • Certain microorganisms are considered to be etiologic agents of disease because they possess virulence factors that are expressed in every host. 
  • Example: Corynebacterium diphtheriae. 
  • Some strains of Pseudomonas aeruginosa also produce toxins which are similar to the toxins of Diphtheria.
  •  Bordetella pertussis which is the causative agent of whooping cough produces toxins that play a role in inhibiting the activity of phagocytic cells and damaging the cells of the respiratory tract.
  1. Microorganism growth
  • Pathogens cause disease by merely growing in the host tissue, interfering with normal tissue function and attracting host immune effectors, such as neutrophils and macrophages.
  • Example: S. pyogenes, M. tuberculosis, Mycoplasma pneumoniae, etc.
  1. Avoiding the Host Response
  • Certain respiratory tract pathogens possess the ability to evade host defense mechanisms.
  •  S. pneumoniae, H. influenza, K. pneumoniae and others possess polysaccharide capsules that serve both to prevent engulfment by phagocytic host cells and to protect somatic antigens from being exposed to host immunoglobulins.
  • Organisms of the respiratory tract and agents that cause diseases: 

Pathogens may or may not cause the respiratory infection but can be present as a part of normal flora.

  •  Some of the pathogens that exist and results in the respiratory infection are referred to as true pathogens. 
  •  Some of the pathogens that are present in the body but never cause an infection until and unless they are met with the favorable conditions are called

as opportunistic pathogens.  

  • Possible pathogen: they are the pathogens that are likely to cause respiratory

infections.

  • Example: Actinomyces spp., Haemophilus influenzae, Enterobacteriaceae, etc.See the source image
  •  Rare pathogen: pathogens that may cause a respiratory infection are rare

pathogens. Example: Coxiella burnetti, Brucella spp., Salmonella spp, etc.  

  •  Definite respiratory pathogen: pathogens that always cause respiratory infections are called as definite respiratory pathogens.
  • Example: Bordetella pertussis, Blastomyces dermatitidis, Legionella spp., etc.
  • Different types of agents that cause respiratory diseases are bacteria, fungi or

viruses.  

  •  Bacterial agents: the bacterial agents that cause respiratory infections are

Mycoplasma spp., Streptococcus pneumoniae and Neisseria meningitides. 

  • Fungal agents: the fungal agents that cause respiratory infections are Candida

albicans, Cryptococcus neoformans and Histoplasma capsulatum.  

  •  Viral agents: the viral agents that cause respiratory infections are human

metapneumovirus, adenovirus, enteroviruses, and herpes simplex virus. 

  • Major respiratory diseases are caused by M. tuberculosis, S. pyogenes and

K.pneumonia.

Sources:

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