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Diabetes - Types, Pathophysiology and Treatment

BY: Shikha Sharma | Category: Biology | Submitted: 2010-11-10 18:56:48
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Article Summary: "Diabetes is a most common disease in many countries including United States and India. It is not a single disease but lead to serious health complications including heart disease, kidney failure and blindness..."

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Diabetes is a most common disease in many countries including United States and India. It is not a single disease but lead to serious health complications including heart disease, kidney failure and blindness.

Classification of Diabetes
A. Diabetes mellitus
It is an endocrine disorder, a group of metabolic diseases characterized by many signs and symptoms. Primary among these are:
a) Kidney failure results into the spillage of sugar into the urine
b) Osmotic effect of glucose results in an excess volume of urine than normal.

1. Type 1 diabetes (Insulin-Dependent Diabetes Mellitus- IDDM)

• Insulin deficiency (little or no circulating insulin) resulting from the destruction of the
beta cells in the islets of Langerhans.
• Predominantly in children so also termed as "juvenile diabetes".
• Loss of cells is mainly a T-cell mediated autoimmune attack
• Etiology is not known but a viral or environmental trigger in genetically susceptible
persons initiate an immunological reaction.

Type I diabetes is fatal unless treated with insulin. Insulin being a protein can not be taken orally; preferred method of administration is through carefully-regulated injections.
For years, insulin required for the treatment comes from the pancreatic cells of cows and pigs. However, the cow and pig insulin differs from human insulin by three and one amino acid, respectively. In recent years, due to advancement in biotechnology, the source of insulin has been replaced with bacteria.

Role of biotechnology
1. Since there is a difference of only one amino acid between pig and human insulin sequence, so it is possible to remove the amino acid that distinguishes them and replace it with the human version. This approach has limited use due to cost-effectiveness.
2. Human insulin gene was introduced into E.coli with an aim to grow recombinant human insulin in large amounts. Insulin is not a glycoprotein, so E.coli and yeast both are able to manufacture a fully functional molecule.
3. Recombinant DNA technology has opened new horizons by manufacturing some modified forms of human insulin that work comparatively more efficiently in lower dosage.
Pancreatic and islet cells transplantation is also recommended in some cases.

2. Type 2 diabetes (Non Insulin-Dependent Diabetes Mellitus- NIDDM)

• About 90% of the people diagnosed with diabetes of this type.
• Insulin deficiency or resistance to the action of insulin
• Such patients are usually obese, have elevated plasma insulin levels, and have down-
regulated insulin receptors.


The development in biotechnology has provided us with several classes of drugs to treat type 2 diabetes. But, the immediate treatment is to reduce the blood glucose levels and the long-term treatment goal is to minimize the diabetes-related complications. Few medications currently in use are:
• Alpha-glucosidase inhibitors: reduce the absorption of glucose from the digestive tract to
lower after-meal glucose levels.
• Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.
• Peptide analogs: Amylin agonist analog slows gastric emptying and suppresses glucagons
• Sulfonylureas are taken orally to trigger the pancreas to make more insulin.

B. Diabetes insipidus (DI)
It is a rare disorder characterized by frequent urination, abnormal increase in fluid intake and often thirst. The main cause is the abnormalities of anti-diuretic hormone (ADH)/vasopressin secretion. The only similarity between the two types of diabetes is increased urination and thirst.

1. Central/neurogenic DI
It is caused by the damage to posterior lobe of pituitary resulting an alteration in the normal functioning and storage of vasopressin hormone. The latter normally acts upon the kidney to reduce urine output by increasing the concentration of the urine. Damage can be either due to head injuries, neurosurgery or genetic susceptibility.

Desmopressin is a synthetic replacement for vasopressin and works by limiting the amount of water eliminated in the urine and making kidneys less responsive to changes in body fluids.

2. Dipsogenic DI

In this, there is suppression of the ADH secretion due to excessive intake of fluids, which increases urine output. The cause is an abnormality in the part of the brain (hypothalamus) that controls thirst mechanism.

Desmopressin and other drugs are usually not recommended for treatment because of the fear of water intoxication. On the contrary, a recent report on a case study, has found an excellent control of polyuria and significant functional improvement after the treatment with low-dose, intranasal desmopressin.

3. Nephrogenic DI
This type of DI is characterized by the inability of kidneys to respond to vasopressin. It can be caused by the intake of a variety of drugs or kidney failure and inherited genetic disorders.

The first line of treatment includes the medications hydrochlorothiazide (HCTZ) or indomethacin. A combination of HCTZ and amiloride is also given sometimes.

4. Gestational DI
It is another form of vasopressin deficiency that occurs during pregnancy. It is either due to a slight damage in pituitary or an excessive production of enzyme vasopressinase from the placenta that destroys the mother ADH.

It is curable with desmopressin.

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