**3. Diabetes and insulin**

There are two types of diabetes, type 1 which is hereditary because of variants in the HLA DQA1, HLA DQB1 and HLA DRB1 genes, which are crucial for forming certain proteins in the body, and type 2 which is acquired due to sedentary lifestyle or family predisposition.

Insulin is composed of two peptide chains, chain A which is made up of 21 amino acids and chain B which is made up of 30 amino acids. Both these chains are linked together by two disulphide bonds. Insulin causes the liver to convert more glucose into glycogen by a process called glycogenesis and primarily forces muscle and fat tissue cells to take up glucose from the blood through the GLUT4 transporter, thus decreasing blood sugar. So, if there is a defect in production of insulin or its uptake, then there will be a rise in blood sugar which can lead to fatal complications if untreated.

**1. Introduction**

16 Ultimate Guide to Insulin

**2. A little bit of history**

**3. Diabetes and insulin**

Laughter is the best medicine. Definitely, if someone has diabetes, insulin would probably be

What is diabetes anyway? Diabetes is the disability of the body to produce or take up insulin, which leads to abnormal carbohydrate anabolism that implies an increase in glucose in the blood. Basically, any food that a person takes in has a certain relative value called 'glycaemic index', which indicates how much food is broken down into sugars and circulated to the rest

However, there is a saying in Chinese, wù jí bì fǎn. In layman terms, this means 'too much of a good thing is bad'; that is where insulin comes into play. Insulin is a protein hormone produced by the beta cells of pancreas and is apparently defective, diminished or even absent in about 415 million people globally, out of which 72.9 million people reside in India according to a 2018 census. It allows body to use sugar (glucose) from carbohydrates in the food that one eats for energy or to store glucose for future use. Insulin helps to keep the blood sugar level

The term 'diabetes' was first used by the Greeks. It was given by Aretaeus of Cappadocia, a Greek physician, (129–199 AD). It means 'to pass through'; they used it to signify the large amount of water consumed and urine produced by diabetics. The term 'mellitus' was added by the Romans, meaning 'sweet as honey', when they noticed that the urine of diabetics was sweet. In 1921, Canadian physician Frederick Banting (November 14, 1891 to February 21, 1941) and medical student Charles H. Best discovered the hormone insulin in the pancreatic extracts of dogs. Because the early insulin preparation required several injections daily, scientists worked hard to find ways to prolong its duration of action. H.C. Hagedorn, in the 1930s, who was a chemist in Denmark, prolonged the action of insulin by adding protamine. The first genetically engineered, synthetic 'human insulin' (first recombinant DNA human insulin) was produced

in 1978 by David Goeddel and his colleagues (of Genentech) using *E. coli* bacteria.

There are two types of diabetes, type 1 which is hereditary because of variants in the HLA DQA1, HLA DQB1 and HLA DRB1 genes, which are crucial for forming certain proteins in the body, and type 2 which is acquired due to sedentary lifestyle or family predisposition.

Insulin is composed of two peptide chains, chain A which is made up of 21 amino acids and chain B which is made up of 30 amino acids. Both these chains are linked together by two disulphide bonds. Insulin causes the liver to convert more glucose into glycogen by a process

needed to be started depending on the clinical scenario.

of the body and utilised by organs for their proper functioning.

from getting too high (hyperglycaemia) or too low (hypoglycaemia).

These complications are lethal, not going to sugarcoat it because these may worsen it for a diabetic! It starts off with increased risk of developing cardiovascular disease, including atherosclerosis, stroke, peripheral artery disease and kidney disease. Diabetic neuropathy, diabetic nephropathy and stroke are some terminal complications.

Diabetes can be controlled in the form of tablets initially, but progressive stages require subcutaneous administration of insulin. Modern methods include transdermal patches or nasal spray.

Administration of insulin can be tricky if it is by the subcutaneous method. Repeated issuing of insulin into the same area can cause lipohypertrophy, a condition of excess accumulation of fat at the site of injection. The most fatal complication that can arise is hypoglycaemia.

Overdose or improper timing of administration of insulin can lead to dangerously low levels of insulin. Low sugar level initially causes hunger, sweating and shaking, but in the long run, it deprives the brain of its fuel, leading to the patient falling into a coma. Hence, it is always advised for a diabetic to have some food around which is ironic.

One can avoid this menace of a disease by altering the modern-day couch potato lifestyle. Keeping oneself hydrated is a good start, exercise is very important as well. Both these components of a healthy manner of living go hand in hand and can naturally lower blood sugar levels. Decreasing the carbohydrate intake and increasing the protein in an individual's diet may also be of great help. Avoidance of sugary food and drinks is a step in the right direction.

Insulin is not a definitive cure for diabetes but is definitely a form of life support. As of now, there is no complete cure for diabetes, but there may be one to wipe it out in the future due to the advancing technologies in the field of science. Strict adherence to medication and exercise can cause the severity of diabetes to lower down, but a normal lifestyle cannot be guaranteed.

If diabetes is so prevalent around the world, it must mean that the population below poverty line and lower middle class are affected as well up to some extent. Insulin can be costly, as it is not a definitive cure, but more of a life support as mentioned above. This is where health insurance is of maximum necessity, which will be shortly discussed in detail.

Diabetes is not something that should be overlooked. Let us say a 68-year-old, uncontrolled diabetic man came to an ophthalmologist with complaints of clouded vision for a long time, and is required to undergo a cataract surgery as soon as possible. If the surgery takes place without letting the sugar levels normalise, this can lead to a lot of postoperative ocular complications such as endophthalmitis, diabetic retinopathy and other diseases which can terminate in complete loss of vision. Such a simple act of patience like waiting for the uncontrolled sugar levels to subside can be detrimental to both the patient and reputation of the doctor.

The way to prevent major infections is via immunisation.

There is sufficient awareness about diabetes in the community, but not sufficient enough about how pernicious it can be if not controlled. Apprehension of such an ailment should be spread by the health sector as well as the media. Medical camps and general hospitals should ensure the illiterate patients are educated to understand the basic knowledge of health-related issues such as diabetes, and that thorough follow-up with the medication is necessary to sustain a healthy lifestyle.

**7. Cytokines**

**8. Hyperglycaemia/glucosuria**

7.8 mmol l

−1

Studies with whole blood, peripheral blood mononuclear cells (PBMCs), and isolated monocytes of diabetics have to be divided into studies with and without stimulation. Without stimulation, tumour necrosis factor alpha (TNF-α) concentrations in patients with DM type 1 [11], interleukin (IL) 6 concentrations in patients with DM type 2 [12] and IL-8 concentrations in DM type 1 and 2 patients [13] have been studied. Elevated resting values of TNF-α, IL-6 and

Insulin – Overview, Infections and Benefits of Immunization and Insurance

http://dx.doi.org/10.5772/intechopen.81346

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Studies with PBMCs and isolated monocytes of diabetic patients after stimulation show the following results: in one study [14] the IL-1 secretion of PBMCs in response to lipopolysaccharide (LPS) was reduced in diabetic (type 1 and 2) PBMCs, while the TNF-α response was the same as in the control cells. In another study, monocytes of DM type 1 patients showed a significantly lower production of IL-1 and IL-6, but again no differences in TNF-α concentrations were measured, after stimulation with LPS, compared with monocytes of DM type 2 patients and non-diabetic controls [15]. Possibly most of the TNF-α already disappeared after the incubation period of 24 h [15]. Neither glucose nor insulin showed any effect on the production of IL-1 or IL-6 in isolated monocytes, so the decreased production after stimulation with LPS seemed an intrinsic cellular defect of diabetic cells. It is possible that the elevated resting value of diabetic cells leads to the induction of tolerance to stimulation, which results in lower cytokine secretions after stimulation. This phenomenon has already been described in non-diabetic cells [16]. Studies of cytokine excretion by PBMCs of non-diabetic patients after the addition of different glucose concentrations have shown comparable results as studies with diabetic cells. One study [17] showed that after the addition of different glucose concentrations, unstimulated monocytes of non-diabetics showed an increased TNF-α and IL-6 response. Another study [18] showed that after pokeweed mitogen stimulation, lower IL-2, IL-6 and IL-10 concentrations were found after the addition of glucose (with a dose-response effect). Possibly, the induction of tolerance, described above, can also explain these results. In other words, the presence of glucose leads to a higher resting cytokine production; after stimulation, however, this cytokine production is impaired compared to the situation without glucose. Another substance which may play a role in the increased basal cytokine secretion is the advanced glycation end products (AGEs, which are products of glucose and lysine or arginine residues). An increased formation of AGEs takes place in poorly regulated diabetic patients [19]. Different studies have shown that binding of these AGEs to non-diabetic cells, without stimulation, leads to an increased cytokine production [17, 20, 21]; so, it seemed that the increased formation of these AGEs in diabetics may be responsible for the increased basal cytokine secretion.

Following the 1985 WHO criteria, DM is defined as a fasting glucose concentration of at least

−1

or higher [22]. As a result of

or a 2-h glucose concentration of 11.1 mmol l

IL-8 were found in diabetic patients compared to non-diabetic controls.
