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    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 adequate 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.
    3 : Diabetes Mellitus is of two types: TYPE-1 –IDDM (Insulin Dependent Diabetes Mellitus) TYPE-2 –NIDDM (Non-Insulin Dependent Diabetes Mellitus) TYPE-3 –Gestational Diabetes
    4 : 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.
    5 : 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.
    6 : 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.
    7 : PATHOGENESIS OF TYPE-1-IDDM Three main factors are involved:- Genetic Environmental Auto-Immunity
    8 : 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. Environmental Factors : Such as viruses ; are mainly involved . 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.
    9 : 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.
    10 : 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.
    12 : 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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