A DETAIL REVIEW ON DIABETES MELLITUS (DM)

About Author:
Amitava Sinha Ray,
Department of Pharmacy, Bengal School of Technology
West Bengal University of Technology,
West Bengal
^*a.amitava.s@gmail.com

INTRODUCTION:-
Diabetes is a chronic disease, which occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. This leads to an increased concentration of glucose in the blood (hyperglycaemia).
The body is unable to produce or unable to properly use and store glucose (a form of sugar). Glucose backs up in the bloodstream and blood glucose or "sugar" to rise too high.

It is a syndrome of impaired carbohydrate, fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin.
When we take some food there glucose is present, in case of DM due to lack of insulin glucose can’t go in to the cell then glucose level is increased into the blood.
DM is totally depend upon the insulin which is secreted from the pancreas specifically from the islet of Langerhans of pancreas

REFERENCE ID: PHARMATUTOR-ART-1692

Physiology of the Pancreas:-
The pancreas is composed of two major types of tissues, -----------
(1) the acini, which secrete digestive juices into the duodenum,
(2) the islets of Langerhans, which secrete insulin and glucagon directly into the blood

The human pancreas has 1 to 2 million islets of Langerhans, each only about 0.3 millimeters in diameter and organized around small capillaries into which its cells secrete their hormones. The islets contain three major types of cells, alpha, beta, and delta cells, which are distinguished from one another by their morphological and staining characteristics.  The beta cells, constituting about 60 per cent of all the cells of the islets, lie mainly in the middle of each islet and secrete insulin and amylin, a hormone that is often secreted in parallel with insulin, although its function is unclear. The alpha cells, about 25 per cent of the total, secrete glucagon. And the delta cells, about 10 per cent of the total, secrete somatostatin.^[3]

Insulin:-
Insulin was discovered in 1921 by Banting and Best. Insulin is a small protein; human insulin has a molecular weight of 5808. It is composed of two amino acid chains, shown in Figure 78–2, connected to each other by disulfide linkages. When the two amino acid chains are split apart, the functional activity of the insulin molecule is lost.

Insulin is composed of two peptide chains referred to as the A chain and B chain. A and B chains are linked together by two disulfide bonds, and an additional disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids.^[3]

1.      Action of Insulin:-
Insulin facilitates glucose transport across the cell membrane.

Glucagon:-
Glucagon, a hormone secreted by the alpha cells of the islets of Langerhans when the blood glucose concentration falls, has several functions that are diametrically  opposed to those of insulin. Most important of these functions is to increase the blood glucose concentration,  an effect that is exactly the opposite that of insulin.  Like insulin, glucagon is a large polypeptide. It has a molecular weight of 3485 and is composed of a chain of 29 amino acids. On injection of purified glucagon into an animal, a profound hyperglycemic effect occurs. Only 1 mg/kg of glucagon can elevate the blood glucose concentration about 20 mg/100 ml of blood (a 25 per cent increase) in about 20 minutes. For this reason, glucagon is also called the hyperglycemic hormone.^[4]

WORLD STATISTICS ABOUT DIABETES MELLITUS:-
WHO estimates that more than 346 million people worldwide have diabetes. This number is likely to more than double by 2030 without intervention.

• 346 million people worldwide have diabetes¹.
• In 2004, an estimated 3.4 million people died from consequences of high blood sugar.
• More than 80% of diabetes deaths occur in low- and middle-income countries.
• WHO projects that diabetes deaths will increase by two thirds between 2008 and 2030.
• Healthy diet, regular physical activity, maintaining a normal body weight and avoiding tobacco use can prevent or delay the onset of type 2 diabetes.

World Diabetes Day (14 November 2013)^[2]
World Diabetes Day raises global awareness of diabetes - its escalating rates around the world and how to prevent the illness in most cases. Started by the International Diabetes Federation (IDF) and WHO, the Day is celebrated on 14 November to mark the birthday of Frederick Banting who, along with Charles Best, was instrumental in the discovery of insulin in 1922, a life-saving treatment for diabetes patients.

1.  About 347 million people worldwide have diabetes.^[2]
There is an emerging global epidemic of diabetes that can be traced back to rapid increases in overweight, obesity and physical inactivity.

2. Diabetes is predicted to become the seventh leading cause of death in the world by the year 2030.
Total deaths from diabetes are projected to rise by more than 50% in the next 10 years.

3. There are two major forms of diabetes.
Type 1 diabetes is characterized by a lack of insulin production and type 2 diabetes results from the body's ineffective use of insulin.

4. A third type of diabetes is gestational diabetes.
This type is characterized by hyperglycaemia, or raised blood sugar, which has first appeared or been recognized during pregnancy

5. Type 2 diabetes is much more common than type 1 diabetes.
Type 2 accounts for around 90% of all diabetes worldwide. Reports of type 2 diabetes in children – previously rare – have increased worldwide. In some countries, it accounts for almost half of newly diagnosed cases in children and adolescents.

6. Cardiovascular disease is responsible for between 50% and 80% of deaths in people with diabetes.
Diabetes has become one of the major causes of premature illness and death in most countries, mainly through the increased risk of cardiovascular disease (CVD).

7. In 2004, an estimated 3.4 million people died from consequences of high blood sugar.

8. 80% of diabetes deaths occur in low- and middle-income countries.
In developed countries most people with diabetes are above the age of retirement, whereas in developing countries those most frequently affected are aged between 35 and 64.

9.  Diabetes is a leading cause of blindness, amputation and kidney failure.
Lack of awareness about diabetes, combined with insufficient access to health services and essential medicines, can lead to complications such as blindness, amputation and kidney failure.

10. Type 2 diabetes can be prevented.
Thirty minutes of moderate-intensity physical activity on most days and a healthy diet can drastically reduce the risk of developing type 2 diabetes. Type 1 diabetes cannot be prevented.

DIFFERENT TYPES OF Diabetes Mellitus:-

I.  Type I or IDDM:-Insulin Dependent Diabetes Mellitus
II. Type II or NIDDM:-Non-Insulin Dependent   Diabetes Mellitus
III. MRDM:-Malnutrition Related Diabetes Mellitus
IV. IGT:-Impaired Glucose Tolerance
V.  Gestational Diabetes:-Occur during pregnancy

I. Type I or IDDM (Insulin Dependent Diabetes Mellitus):-
The cells in the pancreas that make insulin are destroyed, causing a severe lack of insulin. This is thought to be the result of the body attacking and destroying its own cells in the pancreas - known as an autoimmune reaction. It is an auto-immune disease where the body's immune system destroys the insulin-producing beta cells in the pancreas. This type of diabetes, also known as juvenile-onset diabetes, accounts for 10-15% of all people with the disease. It can appear at any age, although commonly under 40. People with type 1 diabetes must inject themselves with insulin.

It's not clear why this happens, but a number of explanations and possible triggers of this reaction have been proposed. These include:

• infection with a specific virus or bacteria;
• exposure to food-borne chemical toxins.

II. Type II or NIDDM:-Non-Insulin Dependent   Diabetes Mellitus
Type 2 diabetes is the most common form of diabetes, affecting 85-90% of all people with the disease. This is characterised by insulin resistance and relative insulin deficiency. The disease is strongly genetic in origin but lifestyle factors such as excess weight, inactivity, high blood pressure and poor diet are major risk factors for its development. Symptoms may not show for many years and, by the time they appear, significant problems may have developed. People with type 2 diabetes are twice as likely to suffer cardiovascular disease. Type 2 diabetes may be treated by dietary changes, exercise and/or tablets. Insulin injections may later be required.

The receptors on cells in the body that normally respond to the action of insulin fail to be stimulated by it - this is known as insulin resistance. In response to this more insulin may be produced, and this over-production exhausts the insulin-manufacturing cells in the pancreas;
1. There is simply insufficient insulin available
2.The insulin that is available may be abnormal and therefore doesn't work properly.

The following risk factors increase the chances of developing Type 2 diabetes:

1.      Increasing age.
2.      obesity
3.      physical inactivity.
4.      Medicine like Alloxan,Streptozocine or steroid can cause DM
5.      Surgical removal of gland.
6.      Tuberculosis of the adrenal gland—primary or secondar

 III.            MRDM (Malnutrition Related Diabetes Mellitus):-
MRDM is caused by a chronic malnutrition state. It is a rare type of diabetes. It occurred with long term malnutrition. MRDM is characterized by insulinopenia, insulin resistance, hyperglycemia and failure of the beta-cells (insulin-producing cells in the pancreas). MRDM is also termed as Tropical Diabetes or Tropical Pancreatic Diabetes Mellitus.

Types of Malnutrition Related Diabetes Mellitus (MRDM)
1.Protein Deficient Diabetes Mellitus (PDDM)
2.Fibrocalculous Pancreatic Diabetes (FCPD)

 IV.            IGT (Impaired Glucose Tolerance)
Impaired Glucose Tolerance (IGT) is the state where the blood glucose levels that are higher than normal, but below the level of a person with diabetes. IGT is a combination of:

• Weakened or damaged secretion of insulin 
• Reduced insulin sensitivity that is insulin resistance

In people with IGT, the rise in blood glucose that occurs after consuming 75g glucose is greater than normal; although not as great as in people with type 2 diabetes.  Fasting blood glucose levels are normal or moderately raised.

IGT can be prevented by increasing physical activity, maintaining a healthy weight, and following a diabetic diet. Weight loss and increased physical activity can reduce insulin resistance and make the insulin produced more effective in controlling blood glucose. 

V. Gestational Diabetes mellitus (GDM)
Gestational diabetes is hyperglycaemia with onset or first recognition during pregnancy. Symptoms of gestational diabetes are similar to Type 2 diabetes. Gestational diabetes is most often diagnosed through prenatal screening, rather than reported symptoms. Risk factors for GDM include a family history of diabetes, increasing maternal age, obesity. While the carbohydrate intolerance usually returns to normal after the birth, the mother has a significant risk of developing permanent diabetes while the baby is more likely to develop obesity and impaired glucose tolerance or diabetes later in life.

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Atiology of Diabetes Mellitus:-
1. Age :-Occur in middle age.50% occur at age of 50years
2. Sex:-Both sex suffer equally but in lower age of male & middle age of female are more affected
3. Heridity:-It may run in families but the nature of the defect is difficult to assess.
4. Infection:-In many case of staphylococcal infection latent diabetes is precipitated
5. Drug:-Certain other drugs, such as alloxan, streptozocin, and thiazide diuretics, are toxic to the beta cells of the pancreas and can cause diabetes
6. Surgical removal of the gland
7. Tuberculosis of the adrenal gland—primary or secondary
8. Certain syndromes (for example, Prader-Willi, Down's, Progeria, and Turner's) may result in a hyperglycemic state; if this state is prolonged, the result can be permanent diabetes.
9. Hepatic disorder:-In chronic and acute hepatic insufficiency there may be impaired storage of sugar in the liver resulting in hyperglycaemia and glycosuria
10. Obesity:-Many middle aged diabetics are obese.

symptoms of diabetes mellitus:

• Excessive thirst and appetite
• Increased urination (sometimes as often as every hour)
• Unusual weight loss or gain
• Fatigue
• Nausea, perhaps vomiting
• Blurred vision
• In women, frequent vaginal infections
• In men and women, yeast infections
• Dry mouth
• Slow-healing sores or cuts
• Itching skin, especially in the groin or vaginal area

COMLICATION OF DIABETES MELLITUS

1.      Neuropathy (nerve disease):-Diabetic neuropathies are the complication of long-term diabetes. It is estimated that 60% to 70% of diabetics have mild to severe forms of nervous system damage. The femoral nerve is commonly involved giving rise to symptoms in the legs and feet. Pain is the chief symptom and tends to worsen at night when the person is at rest. It is usually relieved by activity and aggravated by cold. Cramping, tenderness and muscle weakness also occur but atrophy is rare.With respect to sexual impotence, diabetes is probably the single most common disease associated with erectile failure.

2.      Retinopathy (eye disease):-Changes occurring in the eye which are distinctive of diabetes involve the narrowing, hardening, bulging, haemorrhaging or severing of the veins and capillaries of the retina. This is a serious complication known as retinopathy and may lead to loss of vision. Visual changes in the earlier stages may include diminished vision, contraction of the visual field, changes in the size of objects or photophobia. In the more advanced stage, total blindness may occur.

3.      Arteriosclerosis (vessel disease):-Atherosclerosis can be accurately described as the end stage of Type 1 and Type 2 diabetes, since the vast majority of diabetes patients will die from an atherosclerotic event. Most commonly these events are cardiovascular in nature (an estimated 60% to 65% of diabetics have high blood pressure) although 20-25% of atherosclerotic events may be cerebrovascular or microvascular.

4.      Nephropathy (kidney disease):-Nephropathy is a common complication of diabetes. albuminuria, nephrotic syndrome of hypertension, proteinuria and edema occurs in less than 10% and renal function is impaired in only one half to three quarters of those patients..

5.      Hypoglycaemia:-The first sign is mild hunger, quickly followed by dizziness, sweating, palpitations, mental confusion and eventual loss of consciousness. Before the condition reaches emergency proportions, most diabetics learn to counteract the symptoms by eating a sweet or drinking a glass of orange juice. In some cases, the only effective measure is an intravenous injection of glucose.

6.      Digestive Disorders:-Based on the 1989 US National Health Interview Survey, diabetics are more likely than the general population to report a number of digestive conditions, including ulcers, symptoms of irritable bowel syndrome, abdominal pain, constipation, diarrhoea and gallstones.

7.      Oral Complications:-Periodontal disease, which can lead to tooth loss, occurs with greater frequency and severity among diabetics..

8.      Ketoacidosis:-Another acute complication more likely to occur in the IDDM is ketoacidosis, a condition caused by a lack of insulin leading to a build-up of ketoacids. Chemical compounds called ketones are one of the natural by-products of fat metabolism. Excessive ketone bodies are formed by the biochemical imbalance in uncontrolled or poorly managed diabetes. The condition known as diabetic ketoacidosis can directly cause an acute life-threatening event, a diabetic coma.

GROUPS OF DRUGS USED IN TREATMENT OF DIABETES MELLITUS
1.      Sulfonylnylurea
2.      Biguanides
3.      Meglitinide Analouges
4.      Thiazolidinediones

SOME PLANTS USED AS ANTIDIABETIC:-^[7]

References:-
1.    who.int/features/factfiles/diabetes
2.    who.int/mediacentre
3.    Text book of Medical physiology by Guyton & Hall
4.    Essential of anatomy and physiology
5.    Essentials of Medical Pharmacology by KD TRIPATHI
6.    Text Book of Medicine by P.C Das
7.    Herbal Medicines for Diabetes Mellitus: A Review by M.Upendra Rao, M.Sreenivasulu

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