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    Review o Pathophysiology of Diabetes Mellitus


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    2 : Introduction Diabetes Mellitus is a metabolic disorder characterized by persistent hyperglycemia (high blood sugar level). Resulting either from inadequate secretion of hormone insulin, an inadequate response of target cell to insulin or combination of these factors. Glucose level in the blood is controlled by several hormone . Insulin is the major hormone which controls the level of glucose in blood. Insulin is secreted by beta-cells of Islet of langerhans of pancreas.
    4 : Diagnostic values for Diabetes Mellitus and other categories of hyperglycaemia.
    6 : Diabetes Mellitus is of three types: TYPE-1 –IDDM (Insulin Dependent Diabetes Mellitus) TYPE-2 –NIDDM (Non-Insulin Dependent Diabetes Mellitus) TYPE-3 –Gestational Diabetes
    7 : TYPE-1 –IDDM It is characterized by loss of the insulin producing beta-cells of islet of langerhans of the pancreas. Sensitivity and responsiveness to insulin are usually normal. This type of Diabetes Mellitus comprises up to 10%. Type-1 IDDM can affect childrens or adults. Common causes: Loss of beta-cells leading to Type-1 IDDM is autoimmune destruction or by antibodies directed against insulin and Islet proteins.
    8 : TYPE-2 - NIDDM Type-2-NIDDM is due to combination of defective insulin secretion and defective responsiveness to insulin or reduced insulin sensitivity. It is quite common ; comprising 90% or more of cases in many population.
    9 : TYPE-3 GESTATIONAL DIABETES It involves combination of inadequate insulin secretion and responsiveness . It develops during pregnancy and improve or disappear after delivery. Individuals at higher risk for Gestational Diabetes include : Obese woman. Those with previous history of glucose intolerance. Any pregnant woman who has elevated fasting, or casual, blood glucose level. Those with a history of gestational diabetes mellitus. Those with a history of large for gestational –age-babies. Strong family history of diabetes mellitus.
    10 : OTHER SPECIFIC TYPES OF DIABETES Genetic defects of ß-cell function Chromosome 20,HNF-4a. Chromosome 7,Glucokinase. Chromosome 12,HNF-1 a. Chromosome 13, Chromosome 13, IPF-1 . Mitochondrial DNA 3243 mutation Others Genetic defects in insulin action Type A insulin resistance Leprechaunism Others Rabson-Mendenhall syndrome Lipoatrophic diabetes Endocrinopathies Cushing's syndrome Acromegaly Phaeochromocytoma Glucagonoma Hyperthyroidism Somatostatinoma Others Diseases of the exocrine pancreas Fibrocalculous pancreatopathy Pancreatitis Trauma / pancreatectomy Neoplasia Cystic fibrosis Haemochromatosis Others
    11 : PATHOGENESIS OF TYPE-1-IDDM Three main factors are involved:- Genetic Environmental Auto-Immunity
    12 : Discussion of TYPE-1 IDDM Genetic Factors : It accounts for about 1/3rd of the susceptibility. In a genetic susceptibility person ; there is a development of Auto-antigen receptors lead to destruction of beta-cells. Susceptibility gene on HLA region in Chromosome-6. It concordance with identical twins 50%. Environmental Factors : Such as viruses ; are mainly involved . Geographical and seasonal variations are also occurred. The environmental factors changes structure features with beta-cell and leads to destruction of beta-cell. Auto-Immunity Factors : Type-1 IDDM is a slow T-cell mediated Auto-immune disease. Destruction of the insulin secretion cell in the pancreatic islets takes place over many years. The pathological changes in the pre-diabetic pancreas in Type-1 IDDM is characterized by Insulinitis. It is the infiltration of Islet with mono-nuclear cells containing activated macrophages ,helper cytotoxic T-lymphocytes, Natural Killer cells, B-lymphocytes.
    13 : Characteristics of Type 1 Diabetes Diabetes-Hypoinsulinemia (?insulin levels) 10% of Diabetic cases Patient require Insulin Age of Onset – Childhood Ketoacidosis –(?ketones in blood)
    14 : PATHOGENESIS OF TYPE -2 NIDDM It is more common than Type-1 IDDM. There is no evidence of immune activation It results mainly due to two defects -: Insulin resistance. Pancreatic beta-cell failure.
    15 : DISCUSSION OF TYPE-2 NIDDM Insulin resistance : Increased hepatic production of glucose and resistance to action of insulin. Insulin resistance may be any one of three general causes :- Out of these three; target tissue defect is the most common cause of Insulin resistance is Type-2 –NIDDM. Pancreatic beta-cell failure :- There is only moderate reduction in the total mass of pancreatic Islet tissues. Which inconsistent with a measurable fall in plasma insulin concentration. When related to blood glucose level; beta-cell number is reduced and glucagon secretion is increased which may contribute to hyperglycemia and caused Type-2-NIDDM. Possible mechanism for beta-cell decomposition include genotoxicity , Intrinsic failure of Insulin production and degranulation of beta-cells.
    16 : TYPE-2 NIDDM
    17 : Characteristics of Type 2 Diabetes Impaired insulin action Insulin secretion is normal or increased-90% of diabetic cases Age of onset: adulthood Associated with obesity Ketoacidosis: rare Most patients don’t require insulin
    19 : DISCUSSION OF ACUTE COMPLICATIONS Hypoglycaemia: Hypoglycaemia in patient of diabetes mellitus is an abnormally low concentration of glucose in the blood caused by insufficient food intake, excessive exercise or overdose with hypoglycaemic agents or insulin. They may include patient of: Advance retinopathy Unstable Angina pectoris. History of Generalized seizures. Hyperglycaemic crisis Diabetic Ketoacidosis : It affect people suffering from Type-1 Diabetes mellitus .Ketoacidosis occurs when body breakdowns Fatty acids and produced them into ketone bodies;which are acidic in nature .Some of them are lost through urine, but those that will remain in the blood and leads to ketoacidosis. Sign of ketoacidosis: a.Nausea b.Vomiting c.Dry skin and mouth d.Low blood pressure . to be contd………
    20 : b. Hyperglycaemic hyperosmolar state: It is much common for people with Type-2 diabetes mellitus to develop the hyperglycaemic hyperosmolar state in face of severe infections or other major incurrent illness. They usually present with dehydration ,circulatory compromise and a change in mental state. Acidosis is more uncommon ,except when related to lactic acidosis due to hypoperfusion. Infections : People with poorly controlled Diabetes are more prone to develop bacterial (anaerobic) , myobacterial and fungal infections. Urinary tract infections result from obstruction or neurogenic bladder . Pyelitis and Pyelonephritis aggravate diabetic neuropathy. Chronic painless infections may destroy a neuropathic and / or ischemic foot. Tuberculosis of respiratory and other organ systems, fungal infections of skin , bacterial infections of urinary tract and anaerobic of deep tissues poses serious health threats , particularly in poor hygenic surroundings.
    23 : DISCUSSION OF SECONDARY COMPLICATIONS OF DIABETES MELLITUS RETINOPATHY : It is characterized by retinal damage such as bleeding in retina due to this retinal damage or retinal detachment occurs from normal position which ultimately leads to cataract or glaucoma. DIABETIC NEPHROPATHY : In this renal capillaries become leaky ; due to this proteins appear in the filterate or urine which is known as proteinurea leads to nephron syndrome. It may cause other kidney disorders such as renal atherosclerosis leads to renal failure. Nephropathy occurs due to Advance Glycation End Product (AGE) accumulation. Glycation mainly occur of collagen and other proteins. Initially ; it is reversible , but later on become irreversible ,but this deposit on renal capillaries. NEUROPATHY : Defect in peripheral Nervous System mainly involves nerves and these become non-functional symptoms include: Disturbance in urinary bladder functioning. Disturbance in bowel functioning. ATHEROSCLEROSIS : Occurs also due to AGE accumulation in blood vessels.
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    25 : MANAGEMENT OF DIABTES MELLITUS INSULIN THERAPY : It is necessary to control hyperglycemia in Type-1 Diabetes Mellitus .Provided hyperglycemia in type-2 diabetes mellitus, patient may given one month trial of diet ,exercise and weight management. An anti- hyperglycaemic agent /insulin will be prescribed in this condition. OBJECTIVE OF INSULIN THERAPY : To eliminate the symptoms of the hyperglycaemia; To achieve optimum control; To reduce microvascular or macrovascular complications of the diabetes mellitus. To treat associated disease. To allow the patient to achieve normal lifestyle as possible. OTHER TREATMENT OPTION :The backbone of the management of the diabetes mellitus is proper diet and regular exercise. Patient with type-2 diabetes may require oral hyperglycaemic agents and/or insulin , while type-1 will need insulin therapy to survive. to be contd…….
    26 : The treatment plan for diabetes mellitus may include: Diabetes education Mealing plan and nutritional recommendation Exercise Anti-diabetic agent Insulin Management of associated diseases and complications. Nutritional Recommendation :The goal for medical nutritional therapy that apply to all persons with diabetes mellitus. To attain and maintain optimum metabolic outcomes, including:- blood glucose level in the normal range; a lipid and lipoprotein profile that reduces the risk for microvascular disease; blood pressure level that reduces the risk for vascular diseases. To prevent and treat the chronic complications of the diabetes i.e. modify nutrient intake and lifestyle as appropriate for prevention and treatment of obesity, dyslipidaemia, cardiovascular disease and hypertension or nephropathy. To address individual nutritional needs , taking into considerations personal cultural preference and lifestyle . To improve health through healthy food choices and physical activity. to be contd…………..
    27 : EXERCISE : Exercise is an extremely important in the management of diabetes because of its effects on blood glucose and free fatty acids. Exercise burn calories and help to control weight ,eases stress ad tension and maintain feeling of well-being. In addition, regular exercise improves the body’s response to insulin and may make oral anti-diabetic drugs and insulin more effective. It also promotes circulation and lower cholesterol and triglycerides levels , thus reducing the level of cardiovascular diseases. Persons with Diabetic should be encouraged to lead a normal life and participate in sports and exercise programmes.
    28 : PHARMACOLOGICAL THERAPHY The Pharmacological therapeutic methods should be consists of following options: Insulin sensitizers Insulin secretagogues a – glucosidase inhibitor Insulin Oral agent may counteract insulin resistance ,improving ß – cell sensing and insulin secretion or control the rate of intestinal glucose absorption. Combination of agents, particularly sulfonylurea plus metformin ,thiazolinidinediones plus metformin have improved the care of diabetic patients and may be used when monotheraphy is ineffective.

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