CHAPTER-1

1. INTRODUCTION
DIABETES MELLITUS

INTRODUCTION OF DIABETES

Diabetes mellitus, or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the pancreas does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). There are three main types of diabetes mellitus (DIABETES MELLITUS). Type 1 diabetes mellitus from the body's failure to produce insulin, and currently requires the person to inject insulin or wear an insulin pump. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". Type 2 diabetes mellitus results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. This form was previously referred to as non insulin-dependent diabetes mellitus (NIDDM) or "adult-onset diabetes". The third main form, gestational diabetes, occurs when pregnant women without a previous diagnosis of diabetes develop a high blood glucose level. It may precede development of type 2 Smother forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes. All forms of diabetes have been treatable since insulin became available in 1921, and type 2 diabetes may be controlled with medications. Insulin and some oral medications can cause hypoglycemia (low blood sugars), which can be dangerous if severe. Both types 1 and 2 are chronic conditions that cannot be cured. Pancreas transplants have been tried with limited success in type 1 diabetes mellitus; gastric bypass surgery has been successful in many with morbid obesity and type 2 diabetes mellitus. Gestational diabetes usually resolves after delivery.

COLUMBIA INSTITUTE OF PHARMACY

Page 1

CHAPTER-1
1.1 CLASSIFICATION:
Type 1 diabetes Diabetes mellitus type 1

INTRODUCTION OF DIABETES

Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in which beta cell loss is a T-cell-mediated autoimmune attack. There is no known preventive measure against type 1 diabetes, which causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults, but was traditionally termed "juvenile diabetes" because a majority of these diabetes cases were in children. "Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.There are many reasons for type 1 diabetes to be accompanied by irregular and unpredictable hyperglycemia, frequently with ketosis, and sometimes serious hypoglycemia, including an impaired counterregulatory response to hypoglycemia, occult infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease). These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes. Type 2 diabetes Diabetes mellitus type 2 Type 2 diabetes mellitus is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type.
COLUMBIA INSTITUTE OF PHARMACY Page 2

CHAPTER-1

INTRODUCTION OF DIABETES

In the early stage of type 2, the predominant abnormality is reduced insulin sensitivity. At this stage, hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver. Gestational diabetes Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2 5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. About 2050% of affected women develop type 2 diabetes later in life. Other types Prediabetes indicates a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2diabetes mellitus. Many people destined to develop type 2dibetes mellitus spend many years in a state of prediabetes which has been termed "America's largest healthcare epidemic. Latent autoimmune diabetes of adults (LADA) is a condition in which type 1 diabetes mellitus develops in adults. Adults with LADA are frequently initially misdiagnosed as having type 2 dibetes mellitus, based on age rather than etiology. Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulinantagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells

COLUMBIA INSTITUTE OF PHARMACY

Page 3

CHAPTER-1
1.2 SINGH AND SYMPTOMS

INTRODUCTION OF DIABETES

In both types of diabetes, signs and symptoms are more likely to be similar as the blood sugar is high, either due to less or no production of insulin, or insulin resistance. In any case, if there is inadequate glucose in the cells, it is identifiable through certain signs and symptoms. These symptoms are quickly relieved once the Diabetes is treated and also reduce the chances of developing serious health problems. Diabetes Type 1: In type 1, the pancreas stops producing insulin due to autuimmune response or possibly viral attack on pancreas. In absence of insulin, body cells dont get the required glucose for producing ATP (Adenosin Triphosphate) units which results into primary symptom in the form of nausea and vomiting. In later stage, which leads to ketoacidosis, the body starts breaking down the muscle tissue and fat for producing energy hence, causing fast weight loss. Dehydration is also usually observed due to electrolyte disturbance. In advanced stages, coma and death is witnessed. Diabetes Type 2: Increased fatigue: Due to inefficiency of the cell to metabolize glucose, reserve fat of body is metabolized to gain energy. When fat is broken down in the body, it uses more energy as compared to glucose; hence body goes in negative calorie effect, which results in fatigue. Polydipsia: As the concentration of glucose increases in the blood, brain receives signal for diluting it and, in its counteraction we feel thirsty. Polyuria: Increase in urine production is due to excess glucose present in body. Body gets rid of the extra sugar in the blood by excreting it through urine. This leads to dehydration because along with the sugar, a large amount of water is excreted out of the body. Polyphegia: The hormone insulin is also responsible for stimulating hunger. In order to cope up with high sugar levels in blood, body produces insulin which leads to increased hunger. Weight flactuation: Factors like loss of water (polyuria), glucosuria, metabolism of body fat and protein may lead to weight loss. Few cases may show weight gain due to increased appetite.

COLUMBIA INSTITUTE OF PHARMACY

Page 4

CHAPTER-1

INTRODUCTION OF DIABETES

Blurry vision: Hyperosmolar hyperglycemia nonketotic syndrome is the condition when body fluid is pulled out of tissues including lenses of the eye, which affects its ability to focus, resulting blurry vision. Irritability: It is a sign of high blood sugar because of the inefficient glucose supply to the brain and other body organs, which make us, feel tired and uneasy. Infections : The body gives few signals whenever there is fluctuation in blood sugar (due to suppression of immune system) by frequent skin infections like fungal or bacterial or UTI (urinary tract infection). Poor wound healing: High blood sugar resists the flourishing of WBC, (white blood cell) which are responsible for body immune system. When these cells do not function accordingly, wound healing is not at good pace. Secondly, long standing diabetes leads to thickening of blood vessels which affect proper circulation of blood in different body parts.

COLUMBIA INSTITUTE OF PHARMACY

Page 5

CHAPTER-1
1.3 CAUSES:
The cause of diabetes depends on the type. Type 1

INTRODUCTION OF DIABETES

Type 1 diabetes is partly inherited, and then triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. A genetic element in individual susceptibility to some of these triggers has been traced to particular HLA genotypes (i.e., the genetic "self" identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 DM seems to require an environmental trigger. The onset of type 1 diabetes is unrelated to lifestyle. Type 2 Type 2 diabetes is due primarily to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including: obesity (defined by a body mass index of greater than thirty), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60-80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.Those who are not obese often have a high waisthip ratio Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugarsweetened drinks in excess is associated with an increased risk. The type of fats in the diet are also important, with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating lots of white rice appears to also play a role in increasing risk. A lack of exercise is believed to cause 7% of cases.

COLUMBIA INSTITUTE OF PHARMACY

Page 6

CHAPTER-1
1.4 PATHOPHYSIOLOGY
Diabetes Mellitus: Pathophysiology

INTRODUCTION OF DIABETES

Fig.1.1- Pathophysiology of daibetes mellitus.

COLUMBIA INSTITUTE OF PHARMACY

Page 7

CHAPTER-1
PATHOPHYSIOLOGY

INTRODUCTION OF DIABETES

The pathophysiology of all types of diabetes is related to the hormone insulin, which is secreted by the beta cells of the pancreas. In a healthy person, insulin is produced in response to the increased level of glucose in the bloodstream, and its major role is to control glucose concentration in the blood. What insulin does is, allowing the body cells and tissues to use glucose as a main energy source. Also, this hormone is responsible for conversion of glucose to glycogen for storage in the muscles and liver cells. This way, sugar level is maintained at a near stable amount. In a diabetic person, there is an abnormal metabolism of insulin hormone. The actual reason for this malfunction differs according to the type of diabetes. Whatever the cause is, the body cells and tissues do not make use of glucose from the blood, resulting in elevated blood glucose (a typical symptom of diabetes called hyperglycemia). This condition is also exacerbated by the conversion of stored glycogen to glucose, i.e., increased hepatic glucose production. Over a period of time, high glucose level in the bloodstream can lead to severe complications, such as eye disorders, cardiovascular diseases, kidney damage, and nerve problems. In Type 1 diabetes, the pancreas cannot synthesize enough amounts of insulin as required by the body. The pathophysiology of Type 1 diabetes mellitus suggests that it is an autoimmune disease, wherein the body's own immune system generates secretion of substances that attack the beta cells of the pancreas. Consequently, the pancreas secretes little or no insulin. Type 1 diabetes is more common among children and young adults (around 20 years). Since it is common among young individuals and insulin hormone is used for treatment, Type 1 diabetes is also referred to as Juvenile Diabetes or Insulin Dependent Diabetes Mellitus (IDDM). In case of Type 2 diabetes mellitus, the insulin hormone secreted by the beta cells is normal or slightly lower than the ideal amount. However, the body cells are not responding to insulin as they do in a healthy person. Since the body cells and tissues are resistant to insulin, they do not absorb glucose, instead it remains in the bloodstream. Thus, the Type 2 diabetes is also

COLUMBIA INSTITUTE OF PHARMACY

Page 8

CHAPTER-1

INTRODUCTION OF DIABETES

Characterized by elevated blood sugar. It is commonly manifested by middle-aged adults (above 40 years). As insulin is not necessary for treatment of Type 2 diabetes, it is known as Noninsulin Dependent Diabetes Mellitus (NIIDM) or Adult Onset Diabetes. The third type of diabetes is called Gestational diabetes. As the term clearly suggests, it is exhibited by pregnant women. Over here, high level of blood glucose is caused by hormonal fluctuations during pregnancy. Usually, the sugar concentration returns to normal after the baby is born. However, there are also instances, in which it remains high even after childbirth. This is an indication for increased risks of developing diabetes in the near future. As already mentioned, the symptoms and effects of all the three forms of diabetes are similar. The noticeable symptoms include increased thirst (polydipsia), increased urination (polyuria), and increased appetite (polyphagia). Other diabetes signs and symptoms include excessive fatigue, presence of sugar in the urine (glycosuria), body irritation, unexplained weight loss, and dehydration. Elevated blood sugar and glycosuria are interrelated; when sugar amount in the blood is abnormally high, the reabsorption by proximal convoluted tubule is reduced, thereby retaining some glucose in the urine.

COLUMBIA INSTITUTE OF PHARMACY

Page 9