Saturday, October 3, 2015

An intro with Diabetes

Diabetes is mainly of two types - Diabetes insipidus - a rare form of diabetes caused by a deficiency of the pituitary hormone vasopressin, which regulates kidney function that may cause frequent urination & Diabetes mellitus - caused by impaired formation of insulin by pancreas mainly due to destruction/decreased responsiveness of islet b-cells.
Diabetes mellitus is characterized by the imbalance in the secretion and/or utilization of insulin which leads to the disorder of carbohydrates (glucose) metabolism in the body. This results the increase or decrease in the blood glucose. Carbohydrates from various dietary sources are the primary exogenous source of glucose which is the main fuel for energy requirement of the body. Therefore, a continuous supply of glucose is necessary to ensure the proper function and survival of all organs. 

Hence, mammals have evolved sophisticated systems to maintain the glucose level in the blood within tight limits, despite large fluctuations in food intake. Homeostatic mechanisms are in place to maintain blood glucose levels with very narrow range protecting the body against hypoglycemia during period of fasting and against the hyperglycemia following the ingestion of a high carbohydrate diet. These goals are met chiefly through the hormonal modulation of the production of glucose by the liver and the peripheral uptake of glucose by skeletal muscle, heart muscle and fat. 

When mammals fast, glucose homeostasis is achieved by triggering expression of gluconeogenic genes in response to glucagon, and when they take a carbohydrate-rich diet, the function is taken over by the insulin for its uptake and utilization peripherally. Defects in carbohydrate metabolizing machinery and consistent efforts of the physiological system to correct the imbalance in carbohydrate metabolism place an over-exertion on the endocrine system, which leads to the deterioration of endocrine control. Continuing deterioration of endocrine control exacerbates the metabolic disturbances leading primarily to hyperglycemia and subsequently, the complication thus developed is called diabetes mellitus.

Type I diabetes is believed to be an autoimmune disease that results in specific immunologic destruction of b-cells of islets of Langerhans's, presence of islet cell antibodies in type I diabetes, lymphocytic infiltration in and around islets (insulitis) and association of type I diabetes with other autoimmune diseases supports the evidence of autoimmunity. About 10% of cases of type I diabetes has other organ specific autoimmune diseases such as Graves’ disease, Addison’s disease or autoimmune thyroiditis. The another presentation of insulin-dependent diabetes mellitus has been recently demonstrated that with immunological testing approximately 10% of patients initially diagnosed of having non-insulin dependent diabetes mellitus (NIDDM) may have a slow onset for IDDM that has been termed latent autoimmune diabetes in adults.

It usually manifest at early age, generally below the age of 40. The plasma insulin levels are low and patients respond to exogenous insulin therapy. The onset is marked by polyurea, polyphagia, and with extreme derangement, ketoacidosis, all resulting from metabolic dearrangements. A catabolic state is reached because of insulin deficiency which results in glucose, fat and protein metabolism. Glucose assimilation in the muscle and liver is greatly reduced and also the stores of glycogen are depleted by increased glycogenolysis. 

This causes glycosuria. The glycosuria induces osmosis and thus results in polyurea, causing profound loss of electrolytes and water. Such a renal water loss and hyperosmolarity causes depletion of intracellular water provokes the osmoreceptors of the thirst centers of brain and causes intense thirst i.e. polydipsia. Due to lack of insulin catabolism of protein and fats occurs resulting in removal of gluconeogenic amino acid from the liver, this result in negative energy balance which in turn leads to increasing appetite i.e. polyphagia. Despite of increased appetite catabolic effect prevails resulting in weight loss and fatigue but the patients are not obese. Thus type I DM is a classic triad of polyurea, polydipsia and polyphagia, weight loss and fatigue.

Type II diabetes, or maturity onset diabetes, or non-insulin dependent diabetes mellitus (NIDDM), is more common and constitutes 80-90% cases of diabetes. The basic metabolic defect in this type of diabetes is either a delayed insulin secretion relative to glucose load (deranged insulin secretion), or the peripheral tissues are unable to respond to insulin (insulin resistance). In this type, the patient is usually 40 years of age at presentation and 80% are obese. Ketoacidosis is not a feature but hyperosmolar non-ketotic coma may be a complication. The pancreas in NIDDM is usually of normal size but with a tendency to fatty infiltration, most probably due to the obesity present in many of these patients.

The type II diabetes is further of two subtypes i.e., obese and non-obese. Obesity is a common finding in type II diabetes. There is impaired insulin sensitivity of peripheral tissues, such as muscle and fat cells to the action of insulin, in obese individuals (insulin resistance). Lack of exercise and obesity are considered major contributors to type II diabetes; roughly 90% of individuals with type II diabetes are obese. These conditions predispose to hyperinsulinemia. Increased insulin resistance results in increased fasting and postprandial b-cells synthesis, which leads to “b-cell burnout” and eventually diabetes. 

The condition of insulin resistance may exist for many years before pancreatic b-cell function actually becomes impaired. Weight reduction in such obese patients produces improvement in the diabetic state. It has been observed that insulin resistance is a factor not only in obese type II diabetes but also in non-obese type II diabetes. In such individuals, the increased insulin resistance of peripheral tissues is due to either decrease in the number of insulin receptors or there is post defect.

Gestational diabetes which refers to the hyperglycemia temporarily during pregnancy in individuals, having inherited liability to develop this disorder. Although this form usually disappears following delivery, 40% of women with gestational diabetes will go on to develop type II diabetes later in life. Other types of diabetes may be secondary to pancreatic disease or removal of pancreatic tissue; secondary to endocrine disease such as acromegaly, Cushing’s syndrome, pheochromocytoma, glucagonoma, somatostatinoma or primary aldosteronism; secondary to administration of hormones causing hyperglycemia.

Iatrogenic diabetes may develop during various forms of therapies by drugs such as antihyperglycemic drugs, thiazide diuretics, preparations containing estrogen, psychoactive drugs, sympathomimetic agents etc. It is also occurring mainly in those patients who are genetically susceptible.

The prevalence of insulin dependent diabetes mellitus (IDDM) is 10% whereas that of non-insulin dependent diabetes mellitus (NIDDM) is 90% of the diabetic population. Diabetes mellitus, the most pervasive and costly chronic disease is afflicted by an estimated 175 million people worldwide. It is a leading cause of adult blindness and end-stage kidneys disease. Additionally diabetics are two to four times more likely to have heart disease or to suffer a stroke .

Therefore, Diabetes mellitus has been recognized as a growing world-wide epidemic by many health advocacy groups including the World Health Organization (WHO). Approximately 5% of the world’s population suffers from diabetes. Independent forecasters have suggested that the global prevalence of the disease will increase from 150 million in 2000 to 220 million in 2010 and to 300 million by 2025. The global burden of diabetes mellitus would rise from 135.3 in 1995 to 300 million in 2025. The WHO has also estimated that diabetes will be one of the leading causes of death and disability within the next quarter century.

India being at top of the world in diabetes cases, known as diabetes capital of the world. The Indians are more prone to diabetes due to the reason being that Indian healthcare policies have by and large emphasized on the prevention of infectious diseases only. Also, with the improved living conditions in India, we are increasingly following western dietary habits unsuited for our environs, adopting sedentary life style, and exposed to psycho-social stress. This has resulted in an unprecedented rise in diabetes population to epidemic proportions during last few decades in India.

Complications related to Diabetes mellitus is that the patients with long-standing diabetes may develop complications affecting the eyes, kidneys or nerves (micro vascular complications) or major arteries. The major arteries are affected in people with diabetes, causing a substantial increase in both in coronary artery disease and strokes as well as peripheral vascular disease. The greatest risk of large vessel disease occurs in those diabetic patients who develop proteinuria or micro albuminuria, which are associated with widespread vascular damage.