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Chapter: Pathology: Endocrine Pathology

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Diabetes Mellitus

Diabetes mellitus (DM) is a chronic systemic disease characterized by insulin defi-ciency or peripheral resistance, resulting in hyperglycemia and nonenzymatic glycosylation of proteins.

DIABETES MELLITUS

 

Diabetes mellitus (DM) is a chronic systemic disease characterized by insulin defi-ciency or peripheral resistance, resulting in hyperglycemia and nonenzymatic glycosylation of proteins. Diagnosis is established by demonstrating either of the following:

         Fasting glucose >126 mg/dL on at least 2 separate occasions

         Positive glucose tolerance test

A glycated hemoglobin (HbA1c) assay is used for certain patient populations. The diagnostic cutoff is 6.5%.

Type 1 diabetes (T1D) represents 10% of cases of diabetes.

         Affects children and adolescents, usually age <20

         Risk factors include Northern European ancestry and specific HLA types (DR3, DR4, and DQ)

         Pathogenesis is a lack of insulin due to autoimmune destruction of β cells (type IV hypersensitivity reaction)

         Patients are absolutely dependent on insulin to prevent ketoacidosis and coma

         Thought to be caused by autoimmune reaction triggered by an infection (Cox-sackie B virus) in a genetically susceptible individual

T1D can present with polydipsia, polyuria, and polyphagia; dehydration and elec-trolyte imbalance; metabolic ketoacidosis; and coma and potentially death. Micro-scopically, lymphocytic inflammation involves the islets of Langerhans (insulitis), leading to loss of β cells and fibrosis of the islets. Treatment is insulin.

Type 2 diabetes (T2D) represents 90% of cases.

         Affects obese individuals, both children and adults

         Approximately 10 million people in the United States are affected (half are undiagnosed), and incidence increases with age

         Risk factors include obesity, increasing age, and genetic predisposition

         Pathogenesis involves relatively reduced insulin secretion; peripheral insulin resistance is the term used for reduced tissue sensitivity to insulin due to decreased numbers of insulin receptors on the cell membranes.

T2D is often asymptomatic, but it can present with either polydipsia, polyuria, and polyphagia, or with hyperosmolar nonketotic diabetic coma. Microscopically, the changes are nonspecific, and can include focal atrophy and amyloid deposition in islets (hyalinization). Treatment is diet/weight loss, oral antidiabetic drugs, and insulin as needed (more common in long-standing cases).

Vascular pathology. Diabetes is a major risk factor for atherosclerosis and its com-plications, including myocardial infarction (most common cause of death), stroke (CVA), and peripheral vascular disease. The vascular disease can lead to atrophy of skin and loss of hair of the lower extremities, claudication, nonhealing ulcers, and gangrene of lower extremities.

Diabetic nephropathy includes glomerular lesions, arteriolosclerosis, and pyelone-phritis.

Diabetic retinopathy. Nonproliferative retinopathy is characterized by microan-eurysms, retinal hemorrhages, and retinal exudates. Proliferative retinopathy is characterized by neovascularization and fibrosis. Diabetics also have an increased incidence of cataracts and glaucoma.

Diabetic neuropathy can cause peripheral neuropathy, neurogenic bladder, and sexual impotence.



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