DIABETES

PHYSIOLOGY 1A FACULTY OF PHARMACY

ZUBAIR ALI L1F13PHMD0066

DEFINATION:
Diabetes mellitus is the disorder of carbohydrate metabolism characterized by impaired ability of the body to produce or respond to insulin and thereby maintain proper levels of sugar(glucose) in the blood. The name diabetes mellitus refers to these symptoms: diabetes, from the Greek diabainein, meaning to pass through, describes the copious urination, and mellitus, from the Latin meaning sweetened with honey, refers to sugar in the urine.

Diabetes is a major cause of morbidity and mortality, though these outcomes are not due to the immediate effects of the disorder. They are instead related to the diseases that develop as a result of chronic diabetes mellitus. These include diseases of large blood vessels (macrovascular disease, including coronary heart disease and peripheral arterial disease) and small blood vessels (microvascular disease, including retinal and renal vascular disease), as well as diseases of the nerves.[3]

Causes
Type 1 diabetes causes Type 1 diabetes is caused by the immune system destroying the cells in the pancreas that make insulin. This causes diabetes by leaving the body without enough insulin to function normally. This is called an autoimmune reaction, or autoimmune cause, because the body is attacking itself. There is no specific diabetes causes, but the following triggers may be involved: Viral or bacterial infection Chemical toxins within food Unidentified component causing autoimmune reaction Underlying genetic disposition may also be a type 1 diabetes cause.

Type 2 diabetes causes Type 2 diabetes causes are usually multifactorial - more than one diabetes cause is involved. Often, the most overwhelming factor is a family history of type 2 diabetes. This is the most likely type 2 diabetes cause. There are a variety of risk factors for type 2 diabetes, any or all of which increase the chances of developing the condition. These include:
Obesity Living a sedentary lifestyle Increasing age

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Bad diet[1]

TYPES AND SYMPTOMS

The main types of diabetes mellitus are: Type 1 diabetes mellitus: results from the body's failure to produce sufficient insulin. Type 2 diabetes mellitus: results from resistance to the insulin, often initially with normal or increased levels of circulating insulin. Gestational diabetes: pregnant women who have never had diabetes before but who have high blood glucose levels during pregnancy are said to have gestational diabetes. Gestational diabetes affects about 4% of all pregnant women. It may precede development of type 2 (or rarely type 1) diabetes. Maturity-onset diabetes of the young (MODY) includes several forms of diabetes with monogenetic defects of beta-cell function (impaired insulin secretion), usually manifesting as mild hyperglycaemia at a young age, and usually inherited in an autosomal-dominant manner. Secondary diabetes: accounts for only 1-2% of patients with diabetes mellitus. Causes include: Pancreatic disease: cystic fibrosis, chronic pancreatitis, pancreatectomy, carcinoma of the pancreas. Endocrine: Cushing's syndrome, acromegaly, thyrotoxicosis, phaeochromocytoma, glucagonoma. Drug-induced: thiazide diuretics, corticosteroids, atypical antipsychotics, antiretroviral protease inhibitors. Congenital lipodystrophy. Acanthosisnigricans. Genetic: Wolfram's syndrome (which is also referred to as DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy and deafness), Friedreich's ataxia, dystrophiamyotonica, haemochromatosis, glycogen storage diseases Common symptoms of diabetes:

Urinating often Feeling very thirsty Feeling very hungry - even though the patient is eating Extreme fatigue Blurry vision Cuts/bruises that are slow to heal Weight loss - even though the patient is eating more (type 1) Tingling, pain, or numbness in the hands/feet (type 2)

TYPE 1 DIABETES MELLITUS

The development of type 1 diabetes mellitus is based on a combination of a genetic predisposition and an autoimmune process that results in gradual destruction of the beta cells of the pancreas, leading to absolute insulin deficiency. There is usually a pre-diabetic phase where autoimmunity has already developed but with no clinically apparent insulin dependency. Insulin autoantibodies can be detected in genetically predisposed individuals as early as 6-12 months of age.

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Approximately 15% of those with diabetes have type 1 diabetes - usually juvenile-onset, but it may occur at any age. It may be associated with other autoimmune diseases. It is characterised by insulin deficiency. There is 30-50% concordance in identical twins and a positive family history in 10% of people with type 1 diabetes. Screening for the diagnosis of diabetes in first-degree relatives of patients with type 1 is therefore reasonable, keeping in mind that the absolute risk is quite low. Associated with HLA DR3 and DR4 and islet cell antibodies around the time of diagnosis. Patients always need insulin treatment and are prone to ketoacidosis. The most at-risk population for type 1 diabetes is Caucasian of northern European ancestry. Incidence is high in Scandinavian people

TYPE 2 DIABETES MELLITUS

Approximately 85% of those with diabetes; they are usually older at presentation (usually >30 years of age) but it is increasingly diagnosed in children and adolescents. Type 2 diabetes is associated with excess body weight and physical inactivity. All racial groups are affected but there is increased prevalence in people of South Asian, African, African-Caribbean, Polynesian, Middle-Eastern and American-Indian ancestry. Those with type 2 diabetes may eventually need insulin treatment.[4]

PROGNOSIS

Type 1 diabetes: Many people with type 1 diabetes have good health but there is an increased risk of blindness, end-stage renal disease, cardiovascular disease and, in some cases, early death. Controlling blood glucose, lipids, blood pressure and weight are important prognostic factors. Type 2 diabetes:

75% of people with type 2 diabetes will die of heart disease and 15% of stroke. The mortality rate from cardiovascular disease is up to five times higher in people with diabetes than in people without diabetes. For every 1% increase in HbA1c level, the risk of death from a diabetes-related cause increases by 21%.

DIAGONOSIS
Blood tests are used to diagnosis diabetes and prediabetes because early in the disease type 2 diabetes may have no symptoms. All diabetes blood tests involve drawing blood at a health care providers office or commercial facility and sending the sample to a lab for analysis. Lab analysis of blood is needed to ensure test results are accurate. Glucose measuring devices used in a health care providers office, such as fingerstick devices, are not accurate enough for diagnosis but may be used as a quick indicator of high blood glucose. Testing enables health care providers to find and treat diabetes before complications occur and to find and treat prediabetes, which can delay or prevent type 2 diabetes from developing. Any one of the following tests can be used for diagnosis: an A1C test, also called the hemoglobin A1c, HbA1c, or glycohemoglobin test a fasting plasma glucose (FPG) test

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an oral glucose tolerance test (OGTT)

Another blood test, the random plasma glucose (RPG) test, is sometimes used to diagnose diabetes during a regular health checkup. If the RPG measures 200 micrograms per deciliter or above, and the individual also shows symptoms of diabetes, then a health care provider may diagnose diabetes.[6]

TREATMENT AND MANAGEMENT

Diabetes can be controlled treated by exercise diet and weight management. If not then the following cures may be adopted. Insulin therapies Diabetics who are unable to produce insulin in their bodies receive regular injections of the hormone, which are often customized according to their individual and variable requirements. Beef or pork insulin, made from the pancreatic extracts of cattle or pigs, can be used to treat humans with diabetes. However, in the United States, beef and pork forms of insulin are no longer manufactured, having been discontinued in favour of human insulin production. Modern human insulin treatments are based on recombinant. Human insulin may be given as a form that is identical to the natural form found in the body, which acts quickly but transiently, or as a form that has been biochemically modified so as to prolong its action for up to 24 hours. Research into other areas of insulin therapy include pancreas transplantation, beta cell transplantation, implantable mechanical insulin infusion systems, and the generation of beta cells from existing exocrine cells in the pancreas. Patients with type I diabetes have been treated by transplantation of the pancreas or of the islets of Langerhans. However, limited quantities of pancreatic tissue are available for transplantation, prolonged immunosuppressive therapy is needed, and there is a high likelihood that the transplanted tissue will be rejected even when the patient is receiving immunosuppressive therapy. Attempts to improve the outcome of transplantation and to develop mechanical islets are ongoing.

Drugs used to control blood glucose levels There are several classes of oral drugs used to control blood glucose levels, including sulfonylureas, biguanides, and thiazolidinedione. Sulfonylureas, such as glipizide and glimepiride, are considered hypoglycemic agents because they stimulate the release of insulin from beta cells in the pancreas, thus reducing blood glucose levels. The most common side effect associated with sulfonylureas ishypoglycaemia (abnormally low blood glucose levels), which occurs most often in elderly patients who have impaired liver or kidney function. Thiazolidinediones, such as rosiglitazone and pioglitazone, act by reducing insulin resistance of muscle and adipose cells and by increasing glucose transport into these tissues. These agents can causeoedema (fluid accumulation in tissues), liver toxicity, and adverse cardiovascular events in certain patients. Furthermore, oral hypoglycaemic agents lower mean blood glucose concentrations by only about 5080 mg per 100 ml (2.84.4 mmol/l), and sensitivity to these drugs tends to decrease with time.

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There are several other agents that can be highly effective in the treatment of diabetes. Pramlintide is an injectable synthetic hormone (based on the human hormone amylin) that regulates blood glucose levels by slowing the absorption of food in the stomach and by inhibiting glucagon, which normally stimulates liver glucose production. Exenatide is an injectable antihyperglycaemic drug that works similarly to incretins, or gastrointestinal hormones, such as gastric inhibitory polypeptide, that stimulate insulin release from the pancreas. Exenatide has a longer duration of action than incretins produced by the body because it is less susceptible to degradation by an enzyme called dipeptidyl peptidase-4 (DPP-4). A drug called sitagliptin specifically inhibits DPP-4, thereby increasing levels of naturally produced incretins. Side effects associated with these drugs are often mild, although pramlintide can cause profound hypoglycemia in patients with type I diabetes.[5]

Bibliography
1 http://www.diabetes.co.uk/diabetes-causes.html 2 http://www.diabetes.co.uk/diabetes-causes.html 3 http://www.britannica.com/EBchecked/topic/160921/diabetes-mellitus 4 http://www.patient.co.uk/doctor/diabetes-mellitus# 5 http://www.britannica.com/EBchecked/topic/160921/diabetes-mellitus/285761/Diet-and-exercise 6http://diabetes.niddk.nih.gov/dm/pubs/diagnosis/

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