DIABETES MELLITUS
diabetes mellitus is a group of metabolic diseases characterised by hyperglycemia resulting from defects in insuline secretion,insuline action or both.diabetes is classified in 2 groups (1)type 1 diabetes caused by beta cells destruction usually leading to absolute insuline deficiency it may be due to immune mediated damage or idiopathic damage.(2) type 2 diabetes may be due to predominantly from insuline resistance with relative insuline deficiency to predominantly secretion defect with insuline resistance.
Pathogenesis of diabetes mellitus (1)type 1diabetes mellitus :by the time type 1 diabetes appears,most of the beta cells in pancrease have been destroyed. A tentative overview of pathologic sequence is like (1)genetic susceptibility to the disease must be present in type 1 diabetes.the major histocompatibility complex (.MHC)is important because susceptibility appears to be linked to certain human leucocyte antigen (HLA,) alleles and because the region controls immune response .MHC is located on short arm of chromosome 6-HLA. Loci are designated by the letter A,B,Ç,and D.the D region has 3 distinct loci,DP,DS and DR.class 1 molecules includes gene product of HLA-A ,B and C loci and are expressed on all nucleated cells. Class 1 molecules are involved in cell mediated immunity and are required for recognition and rejection of all foreign cells and of intrinsic cells that have been altered by viral infection or malignant disease.class 2 molecules are encoded at D sites and are expressed only on B lymphocytes ,tissue and circulating macrophages ,endothelial cells and some activated T lymphocytes.approximately 95% of white patients with type 1 diabetes have either DR3 and DR4 antigen and 55 to 60% have both DR3 and DR4. In other ethanic groups HLA - linked susceptibility to diabetes may involve different alleles.(2)environmenral factor for type 1 diabetes ordinarily initiate the process like (1)viruses the viral hypotheses gained support from studies showing that certain starins of encephalomyocarditis virus cause diabetes in genetically susceptible mice.congenital rubbella is associated with subsequent development of IDDM in about 20% of affected individuals presumably viral infection of pancrease could induce diabetes by either direct inflammatory distruption of islets or induction of immune response.(2)exposure to cow's milk products early in life predeaposes to autoimmune diabetes.bovine albumin induces autoimmunity through mechanism of molecular mimicry. it share structural homology with 69-kDa protein present on surface of pancreatic beta cells.
. (2) type 2 diabetes melittus : it has 2 physiological defect (à)insuline resistance (b)abnormal insulin secretion. Three phases can be recognised in usual clinical sequence.(1)plasma glucose is normal despite insulin resistance because insuline levels are elevated for compsating insulin resistance. (2)insulin resistance does not change but insulin secretion decline,resulting in fasting hyperglycemia and overt diabetes.(3)insuline resistance worsoens,so that despite elevated insulin cocentration ,post prandial hyperglycemia develops. The mode of inheritance of type 2 DM is unknown.there is no association between HLA and true type 2 diabetes there us no consistent genetic abnormality has been implicated in its causation and although insulin resistance is associated with decreased numbers of insulin receptors,the bulk of the resistance is post receptor in type.the environmental factors like physical inactivity ,generous dietary intake and degree of obesity influences the occurrence of type 2 diabetes.the thirty phenotype hypothesis -individuals with low birth weight appear to have higher risk of type 2 diabetes particularly if they become obese in later life. This hypothesis suggests that intra uterine malnutrition leads to defective pancreatic development .such individuals may become susceptible to diabetes,hypertension and heart disease in later life.there are some risk factor for development of type 2 diabetes like age more than 45 yrs,overweight patient bmi more than 25,family history of diabetes,habitual physical inactivity,previously identified ifg or igt,history of hypertension,hypercholesterimiea,polycystic ovarian syndrome,and hystory of vascular disease etc
Clinically diabetes is characterised by sudden onset of symptoms in children and slow gradual onset in adults.patients may present with polyuria ,polyphagia,polydipsia ,weight loss ,weakness and lassitude,puritus vulvae in female or balanitis in male,loss of libido and erectile dysfunction,blurring of vision.
Clinically diabetes can be diagnosed by above symptoms and sign but concorent diagnosis can be made by blood glucose mesuement in laboratory (1)symtomps of diabetes plus casual plasma glucose concentration more than 200 mg/DL,casual is define as any time of day without regar to time since last meal.(2)fasting plasma glucose more than 126 mg/DL .fasting is define as no caloric intake for at least 8 hours.(3)2 hours post load glucose more than 200 mg/DL . the test should be performed using a glucose load containing the equivalent of 100g or 75 g anhydrous glucose dissolved in water.
diabetes mellitus is a group of metabolic diseases characterised by hyperglycemia resulting from defects in insuline secretion,insuline action or both.diabetes is classified in 2 groups (1)type 1 diabetes caused by beta cells destruction usually leading to absolute insuline deficiency it may be due to immune mediated damage or idiopathic damage.(2) type 2 diabetes may be due to predominantly from insuline resistance with relative insuline deficiency to predominantly secretion defect with insuline resistance.
Pathogenesis of diabetes mellitus (1)type 1diabetes mellitus :by the time type 1 diabetes appears,most of the beta cells in pancrease have been destroyed. A tentative overview of pathologic sequence is like (1)genetic susceptibility to the disease must be present in type 1 diabetes.the major histocompatibility complex (.MHC)is important because susceptibility appears to be linked to certain human leucocyte antigen (HLA,) alleles and because the region controls immune response .MHC is located on short arm of chromosome 6-HLA. Loci are designated by the letter A,B,Ç,and D.the D region has 3 distinct loci,DP,DS and DR.class 1 molecules includes gene product of HLA-A ,B and C loci and are expressed on all nucleated cells. Class 1 molecules are involved in cell mediated immunity and are required for recognition and rejection of all foreign cells and of intrinsic cells that have been altered by viral infection or malignant disease.class 2 molecules are encoded at D sites and are expressed only on B lymphocytes ,tissue and circulating macrophages ,endothelial cells and some activated T lymphocytes.approximately 95% of white patients with type 1 diabetes have either DR3 and DR4 antigen and 55 to 60% have both DR3 and DR4. In other ethanic groups HLA - linked susceptibility to diabetes may involve different alleles.(2)environmenral factor for type 1 diabetes ordinarily initiate the process like (1)viruses the viral hypotheses gained support from studies showing that certain starins of encephalomyocarditis virus cause diabetes in genetically susceptible mice.congenital rubbella is associated with subsequent development of IDDM in about 20% of affected individuals presumably viral infection of pancrease could induce diabetes by either direct inflammatory distruption of islets or induction of immune response.(2)exposure to cow's milk products early in life predeaposes to autoimmune diabetes.bovine albumin induces autoimmunity through mechanism of molecular mimicry. it share structural homology with 69-kDa protein present on surface of pancreatic beta cells.
. (2) type 2 diabetes melittus : it has 2 physiological defect (à)insuline resistance (b)abnormal insulin secretion. Three phases can be recognised in usual clinical sequence.(1)plasma glucose is normal despite insulin resistance because insuline levels are elevated for compsating insulin resistance. (2)insulin resistance does not change but insulin secretion decline,resulting in fasting hyperglycemia and overt diabetes.(3)insuline resistance worsoens,so that despite elevated insulin cocentration ,post prandial hyperglycemia develops. The mode of inheritance of type 2 DM is unknown.there is no association between HLA and true type 2 diabetes there us no consistent genetic abnormality has been implicated in its causation and although insulin resistance is associated with decreased numbers of insulin receptors,the bulk of the resistance is post receptor in type.the environmental factors like physical inactivity ,generous dietary intake and degree of obesity influences the occurrence of type 2 diabetes.the thirty phenotype hypothesis -individuals with low birth weight appear to have higher risk of type 2 diabetes particularly if they become obese in later life. This hypothesis suggests that intra uterine malnutrition leads to defective pancreatic development .such individuals may become susceptible to diabetes,hypertension and heart disease in later life.there are some risk factor for development of type 2 diabetes like age more than 45 yrs,overweight patient bmi more than 25,family history of diabetes,habitual physical inactivity,previously identified ifg or igt,history of hypertension,hypercholesterimiea,polycystic ovarian syndrome,and hystory of vascular disease etc
Clinically diabetes is characterised by sudden onset of symptoms in children and slow gradual onset in adults.patients may present with polyuria ,polyphagia,polydipsia ,weight loss ,weakness and lassitude,puritus vulvae in female or balanitis in male,loss of libido and erectile dysfunction,blurring of vision.
Clinically diabetes can be diagnosed by above symptoms and sign but concorent diagnosis can be made by blood glucose mesuement in laboratory (1)symtomps of diabetes plus casual plasma glucose concentration more than 200 mg/DL,casual is define as any time of day without regar to time since last meal.(2)fasting plasma glucose more than 126 mg/DL .fasting is define as no caloric intake for at least 8 hours.(3)2 hours post load glucose more than 200 mg/DL . the test should be performed using a glucose load containing the equivalent of 100g or 75 g anhydrous glucose dissolved in water.